All about: the rare diseases [2]

Diseases and conditions

  • What is Neurofibromatosis
  • It is ITP (immune thrombocytopenia, primary)
  • What is Angelman Syndrome
  • What is Cushing's syndrome
  • What is Klinefelter Syndrome
  • What is the Patau syndrome
  • What is Rett syndrome
  • What is Turner syndrome
  • What is Williams syndrome

What is Neurofibromatosis

It is known as neurofibromatosis to a set of rare diseases of genetic cause and are mainly characterized by the development of multiple benign, i.e. non-cancerous, tumors in different nerves of the body and the skin; as well as the formation of spots in the variations in pigmentation (areas hyperpigmented or hypopigmented) skin.
This disease was first described by a German physician named Friedrich Daniel von Recklinghausen in 1882, and from that moment was coined the term of Von Recklinghausen's disease or neurofibromatosis type 1 (NF1) as it is known at present.
There is also the neurofibromatosis type 2 (NF2) or acoustic neurofibromatosis, but it hardly constitutes 5% of all cases of neurofibromatosis.
The prevalence of neurofibromatosis type 1 is approximately one case among 3,000 people, so it is estimated that roughly two million concerned must exist in the world. Regarding neurofibromatosis type 2, it is estimated that its prevalence is a case between 45,000 people.

Causes of neurofibromatosis

Scientific evidence has shown that in the case of the neurofibromatosis type 1 (NF1) there is an alteration in a gene (mutation) on chromosome 17. This gene regulates the production of a protein called neurofibromin, whose main function is to inhibit the appearance of tumors. Mutations occur spontaneously in 50% of patients from unknown causes, and the other 50% of the cases the mutation is inherited from parents to children in a way autosomal dominant.
But what the dominant autosomal inheritance? It is the heritage not sex-linked, which occurs when the father or the mother to her son inherit a gene with a mutation that is capable of causing disease, because the mutated gene dominates the normal gene. Then if one of the parents is a carrier of disease and the other is not, the probability that each son inherit the mutated gene is 50%.
In the neurofibromatosis type 2 (NF2) mutation is located in a gene of chromosome 22. Around 33 mutations in this gene have been described, and all cause the loss of the ability to suppress the formation of tumors. It is inherited from parents to children, in the same way as NF1 autosomal dominant, and you can also find cases of absence of family history because spontaneous mutation in the affected patient have been generated.

Symptoms of neurofibromatosis type 1 (NF1)

There are three main signs that define the majority of patients with neurofibromatosis type 1 (NF1) and are called major signs:
  • Light brown skin spots, known as Café au lait spots, which circumscribe areas rounded or oval, are flat and are caused by an excess in the accumulation of melanin (skin pigment). They tend to appear since childhood (from the first year of life) and its size increases as the child grows. In terms of their number, they can vary from one or two spots to be more than six spots; they are considered very valuable from the diagnostic point of view, because they occur in 10-20% of patients with NF1. They are found mainly in the skin of the trunk, also observed small freckles in other areas such as the neck, armpits, or groin region. These stains do not have treatment, but have no risk of malignant transformation, i.e., do not cause skin cancer.
  • Neurofibromas, which can be dermal (are benign tumors that occur in skin and nerves); they are of variable size, shape and coloration. They appear during puberty and adolescence progressively increasing throughout life. Do not produce pain, but if itching or stinging. There is a type of neurofibroma affecting large groups of nerves known as plexiform neurofibromas, which it may have babies affected by the disease at the time of the birth. Another type of neurofibromas can affect vision, and are those who are located in the optic nerve (second cranial nerve) and the retina, thus hindering the passage of nerve impulse to the brain from the outside world.
  • The so-called Lisch nodules (hamartomas pigmentary): are rounded elevated lesions of yellow color which affect the iris (pigmented area of the eye). 1 over six years are observed in 90% of patients with neurofibromatosis type. These nodules do not alter the patient's visual ability and are difficult to observe with the naked eye, so it must be evaluated by specialists in Ophthalmology (through a slit-lamp).
Besides, there are other signs of neurofibromatosis, called minors because they occur in a highly variable percentage of patients with neurofibromatosis type 1. Among them are: low height (stature) and large, i.e. with an increased head circumference (macrocephaly) heads.
Some complications that can occur in patients with NF1 are: difficulty to develop the language, learning disabilities which can occur in up to 50% children, deviation of the spine (scoliosis), malignant tumors of muscles and nerve endings (neurosarcomas), elevation of blood pressure, pathological curvatures of the bones of the leg (tibia and fibula) and that predispose to fractures, seizures (epilepsy) , among others.

Symptoms of neurofibromatosis type 2 (NF2)

The neurofibromatosis type 2 (NF2) presented as most relevant characteristic the emergence of benign tumors on the nerve, which is responsible for hearing, i.e. the par 8th cranial or nerve vestibulocochlear, which also has participation in the maintenance of posture and balance.
Tumors often affect the two ears, being able to appreciate the onset of symptoms at the beginning of adolescence. Then the patient complains of two main symptoms: progressive hearing or deafness, and frequent falls loss, problems with balance.
In the skin, Milky coffee spots also exist in this type of neurofibromatosis, but less frequently than in NF1. The spots are round edge flat and darken in the influence of the Sun on them. They have no risk of malignization and also do not have treatment.
From the eye point of view, patients with NF2 may present opacities in the lens (cataracts).
Among the complications of neurofibromatosis type 2 can be found: benign tumors of the brain, this causes an increase in pressure inside the skull (increased intracranial pressure), causing severe headaches, vomiting, blurred vision and even seizures. It can also be complicated with benign tumors in the spinal column and other benign tumors on the skin called schwamnomas, which are painful, in contrast to dermal neurofibromas in NF1, which are painless.

Diagnosis of neurofibromatosis

The signs and symptoms of the patient are key to the diagnosis of neurofibromatosis. Thus, multiple benign tumors of skin, nerves and the Café au lait spots, as well as the knowledge of family history are of vital importance.
Imaging studies featured in these pathologies are computed axial tomography (CT) and the magnetic resonance (NMR), which allow the detection of brain tumors, spine and tumors of the auditory nerve. Tests that assess the proper functioning of the conduction of sound through hatred should be performed to assess the sense of hearing.
In some cases, it may be necessary to do a biopsy of the neurofibromas to help confirm the diagnosis.
From the genetic point of view, the tests are performed by extracting DNA from the patient and their relatives in order to detect possible mutations responsible for the disease, chromosome 17 for neurofibromatosis type 1, both chromosome 22 to neurofibromatosis type 2.
Genetic counseling: when any of these conditions are detected in a family and one of their members manifest desires of paternity or maternity, there are two possibilities:
  • Preimplantation genetic diagnosis, which allows you to select a healthy embryo for its later implantation into the womb.
  • Prenatal diagnosis, which would be conducted by the detection of any of the mutations in the fetal cells during pregnancy, either by villus sampling biopsy, amniocentesis or ultimately funiculocentesis.

Treatment of neurofibromatosis

· As a high percentage of rare and genetic diseases, there is currently no specific treatment for neurofibromatosis. It is recommended that patients should be managed by a multidisciplinary group of specialists such as pediatricians, neurosurgeons, ophthalmologists, dermatologists, geneticists, oncologists and psychologists, among others.
· Neurofibromas, depending on their location in the body, if they commit a vital organ, if they cause pain or not, they should be evaluated for their possible surgical removal. If the malignant transformation of some of the tumors detected other targeted therapies to treat this tumor in particular will be needed.
· The management of chronic pain with painkillers, antidepressants and drugs for anxiety (anxiolytic) is necessary in some patients with neurofibromatosis.

Prognosis of neurofibromatosis

· If there are no complications, the life expectancy of people suffering from neurofibromatosis can become very similar to the one of a healthy individual, however, if they develop a malignant tumor (cancer) their expectations of life could be shortened.
· The most important thing is that diagnosis is made as soon as possible and awareness of the disease. Both the patient and family members should receive the necessary education for the management of the disease and know their potential complications. Some patients who have learning and language problems can suffer school failure and social problems, so it is good to detect it to try to give solution.

It is ITP (immune thrombocytopenia, primary)

It primary immune thrombocytopenia (ITP) is a disease of autoimmune origin in which there is a low number of platelets (which is known as thrombocytopenia or thrombocytopenia) due to increased platelet destruction and, to a lesser extent, to a defect in its production. We say it has an auntoinmune origin because it's own immune system of the patient who produces antibodies that destroy platelets in the blood and prevent its production in the bone marrow. Having a low number of platelets, patients have more risk of bleeding and possible bleeding. It can affect both children and adults.
Today the term idiopathic thrombocytopenic purpura or immune is unused is called primary immune thrombocytopenia (ITP in Spanish and ITP in English) or secondary.
There is no data on the prevalence or incidence of exact of ITP in Spain, although some experts estimate that 5,000 cases it round. In other parts of the world, such as United States, estimated that the incidence of ITP in adults round six cases per 100,000 inhabitants, while the prevalence in adults is located in United Kingdom in 1.6 per 100,000 people. What is clear is that the incidence of this disease is increasing in recent years.

Causes of primary immune thrombocytopenia (ITP)

Patients with PTI create autoantibodies that are aimed to the membrane of platelets and megakaryocytes (the platelets in the bone marrow precursor cells), which occurs a destruction of platelets at the spleen and a decrease in the production of platelets at the spinal cord level.
In the majority of cases, the cause that triggers the production of autoantibodies against platelet is unknown, especially in adults. However, in children, in many cases, the PTI occurs after viral infection or immunization using live attenuated virus.
There are other so-called secondary autoimmune thrombocytopenia where the cause is known, for example, associated with common variable immunodeficiency, autoimmune diseases, pregnancy, infection by the hepatitis C virus or infection by HIV. Autoimmune thrombocytopenia secondary to drugs is also frequent.

Symptoms of ITP

The way in which ITP, is presented as well as their characteristic signs and the clinical development of the disease are highly variable, which complicates much diagnosis, the choice of the adequate treatment and follow-up of patients, who clearly affected their quality of life.
Patients with primary immune thrombocytopenia they may not have symptoms or they may have different gravity-hemorrhagic manifestations, which depends mainly on the number of platelets.
Characteristic is the presence of petechiae, which are small eruptions on the skin or in the mucous membranes, such as red-purplish spots, caused by the output of red blood cells through the wall of the blood vessels. The petechiae do not disappear or are bleached by compressing them. This characteristic distinguishes them from other skin lesions papular which can be similar (such as those caused by bites of insects, allergies, infections...) that duty is a simple vasodilation are bleached by compressing them with your finger.
When the petechiae are greater than 3 mm are called purple, hence comes the name of this disease. Greater than 1-2 cm purpuric lesions are referred to as bruising, which is popularly known as hematoma or bruising.
The petechiae, purpura, or ecchymosis appear with more prevalent in the lower third of the leg, to be part of the body where the blood vessels are under greater pressure. They can also appear after small injuries.
In addition, there may be bleeding by the mucous membranes, such as bleeding through the nose (epistaxis), bleeding from the gums or vaginal bleeding. More uncommon form it produced more severe bleeding as the gastrointestinal, joints or brain.

Diagnosis of ITP

The diagnosis of primary PTI is defined by thrombocytopenia (< 100,000 platelets/µl of blood) in the absence of other associated causes. There is no specific test for its diagnosis, therefore, it will have to reach him after having excluded other causes of thrombocytopenia, as infections (hepatitis C, HIV...), use of drugs, other autoimmune diseases, etc. For this reason, the clinical history along with laboratory parameters are essential to make the diagnosis of ITP.
The figures in the blood red blood cells (erythrocytes) and white blood cells (leukocytes) are usually normal. If you notice the blood under a microscope, testing is called peripheral blood smear, larger than normal but a few platelets are. Studies evaluating the blood clotting do not often show abnormalities.
Sometimes performed a bone marrow biopsy, which is the body where blood, occurs to rule out other diseases that could explain the decrease in platelets. It is usually done in the case of PTI's atypical presentation, as in people older than 40 years, when there are associated alterations of white or red blood cells, or when there is a good response to treatment.
Also look for the presence of blood antiplatelet antibodiescan be. This test is not very sensitive (can be negative in many cases from PTI), but is quite specific (if it is positive, usually indicates that we we have an PTI).

Treatment of ITP

The therapeutic management of ITP must taken into account not only the platelet number, but also the hemorrhagic manifestations and associated diseases of the patient.
Treatment of PTI aims get one adequate platelet number (generally > 30,000 platelets/µl) to prevent bleeds with the least number of side effects of the medications used. The risk of bleeding should be individualized according to associated diseases, age of the patient (there is increased risk of bleeding in children and the elderly) or in those who must undergo major surgery, so the platelet number that we want to reach with treatment may vary according to circumstances.
On the other hand, the treatment is unnecessary in many patients who have PTI. For example, in general, patients with mild thrombocytopenia having no hemorrhagic manifestations or serious illnesses do not treat. However, there are certain situations in which these patients should receive treatment, such as major surgical interventions or pregnancy.

What is the treatment of ITP

The treatment of primary immune thrombocytopenia consists of:


Currently recommended administration of prednisone at doses of 1 mg per kilo of weight and day for 21 days, then go down the dose gradually. There are different treatment regimens with other corticosteroids such as dexamethasone or methylprednisolone. Around 80% of patients respond to corticosteroids. The side effects of steroids used in the long term are, for example, diabetes mellitus, cataracts, weight gain, high blood pressure or osteoporosis.

Gamma globulins

The intravenous gamma globulin may be used, associated or not to corticosteroids, if you require a rapid increase (urgent cases) in the number of platelets. Globulins are antibodies that inhibit harmful antibodies that the body is producing and which are causing the destruction of platelets. More than 80% of the cases respond positively, but its effect is transient.

Splenectomy (removal of the spleen)

In case of failure to Corticoid treatment, well because there have been multiple relapses of the disease or because the patient does not respond, the next step is to start a second-line treatment. Splenectomy is considered a second-line option, although there are other options with drugs that will be detailed in subsequent paragraphs. To indicate a Splenectomy should be assessed, mainly, the age of the patient (in children is usually not perform), lifestyle, time since diagnosis (recommended wait between 6-12 months due to spontaneous healing), the number of platelets that has the patient, hemorrhagic manifestations and therapeutic preferences. Between 75-85% of patients achieve a quick response after the intervention, being durable responses in two thirds of cases. The mortality of Splenectomy is 0, 2 - 1%. The risk of bacterial sepsis postesplenectomia is 1%, so it is recommended vaccination against meningococcus, Pneumococcus and Haemophilus influenzae B before the intervention.

The thrombopoietin receptor agonists

(Romiplostim and eltrombopag)

These drugs have been recently approved for patients who have not responded to Splenectomy or who cannot make it by contraindication or impossibility of the surgery. These drugs have had a big scientific development into human clinical trials and its mechanism of action is totally different from the of the classic drug of ITP, since they increase platelet production by stimulating the thrombopoietin (TPO) receptor without modifying the immune response of the patient. They present different routes of Administration: eltrombopag is administered orally and the romiplostin subcutaneously. They have an efficiency of about 80% and they must be administered chronically. Maximum responses attained with both drugs are very fast, around two weeks, and are durable. Described most often after their side effects are mild, such as headache, although there are other less frequent that the doctor must control.

Other drugs

For patients with PTI refractory to Splenectomy and trombopoyeticos agents, treatment options are many, but the response rate and duration are very variable. There are no controlled studies that have evaluated or relative to its effectiveness. Treatments considered in these cases are: agents that suppress/immunomodulators (azathioprine, Cyclosporine, danazol, Dapsone, Mycophenolate), rituximab (monoclonal antibody that inhibits the type of white blood cell that produces harmful antibodies for the patient), chemotherapy alone or in combination, or transplantation of hematopoietic progenitors.

Platelets trasfusion

It only occurs if there is a hemorrhage with vital irrigation, because platelets are destroyed quickly and its beneficial effect is very brief.

Tips for patients with PTI

In addition to the treatments, there are some tips you should follow patients with PTI:
  • They should avoid activities that expose them to trauma, such as for example the physical contact sports.
  • Refrain from taking aspirin and other anti-inflammatory drugs, which can affect the function of platelets.
  • They should not receive intramuscular medications, because there is the risk of bruising inside the muscle.
  • They have to be evaluated and followed by a physician hematologist.

What is Angelman Syndrome

Angelman Syndrome is a neurological disease of genetic cause that has the following features:
  • Severe mental retardation.
  • Severe impairment of speech (use small words or even complete absence of speech).
  • (Disorder affecting balance and coordination) ataxia and/or tremors of the extremities.
  • Conduct and peculiar behavior: happy with permanent smile and frequent laughter appearance, increased excitability.
  • Microcephaly (the circumference of the head is smaller than normal for the age and the sex of the child), and seizures.
It was first described in 1965 by English pediatrician Harry Angelman, who observed three children who had similar characteristics that nobody had described so far, thinking that it could be a new syndrome. He called these children by their physical characteristics, 'puppet children'. A couple of years later, Bower and Jeavons, observed that there were others affected by this syndrome, and called it 'happy puppet syndrome', a term which would be used until 1982, when it was replaced by Angelman Syndrome, in honor of its discoverer.
The exact incidence of Angelman syndrome is not known with accuracy, but it is estimated to affect 1 in every 20,000-25,000 newborns, which, due to its low frequency, is considered a rare disease. It affects both sexes equally and there is no dominance in a particular race. People who suffer from this syndrome not present alterations at birth, and retardation of the development can start to be seen around 6-12 months of age. The most common age at diagnosis is between three and seven years, when the characteristic behaviors and the clinical features are made more obvious. All of these traits do not need to be present to be able to make the diagnosis.
Among the various causes of chromosomal alteration in Angelman Syndrome, the most common is the deletion (loss of a piece of chromosome spreading of genetic material) from a fragment of chromosome 15 inherited from the mother. This disease does not have a classic inheritance pattern, and the risk of that again depends on the causes that gave origin. The diagnosis is based on clinical and laboratory findings, but a definitive diagnosis is not always achieved. The treatment is very complex and is based on a multidisciplinary treatment, which seeks to reduce or lessen the symptoms.
The degree of involvement of the patients presenting with Angelman syndrome is highly variable and depends, among other things, the genetic alteration that causes the syndrome. For example, when it is caused by a deletion the severity of the symptoms is greater than when the cause is another. On the other hand, the physical characteristics and behavior of the affected change over time, as the individual will develop, so that symptoms in children are different from the adult. In this way, the treatment and participation in different therapies (physical, occupational, communication) you should mold to different difficulties according to every stage of life. Apart from the described problems, sexual development of patients with Angelman syndrome is complete, health status is good and they have a normal life expectancy.

Causes of Angelman Syndrome

Angelman Syndrome is a genetic disease caused by alterations of the UBE3A gene, located on chromosome 15. All mechanisms known so far to cause Angelman Syndrome produces an affectation of this gene on chromosome 15 from the mother. In all cases, the symptoms are similar (mental retardation, impairment of speech, peculiar behavior...), although depending on the cause, involvement may be more or less severe:
  • The most frequent of Angelman Syndrome (up to 70% of cases) is deletion of the maternal chromosome in the region 15q12, where resides a gene called UBE3A. A deletion is the loss of a piece of chromosome, which breaks down and is separated from the rest of genetic material. When Angelman syndrome occurs for this reason, the involvement of the child is severe enough.
  • In a small percentage of cases, Angelman syndrome is caused by inheriting two chromosomes 15 from the father and no mother, what is known in medical terms as uniparental disomy. In this case, the involvement tends to be less severe, because physical development is better, there is no such involvement and coordination of movements and the prevalence of seizures is less.
  • Other causes of Angelman Syndrome are defects in the center of the stamp or the mutation in the gene of the UBE3A, derived from chromosome 15 from the mother. In these cases the clinical involvement is generally not so severe.

Angelman Syndrome signs and symptoms

Angelman Syndrome is a neurological disorder that is associated with mental retardation. It has a genetic origin, and causes in the development, learning and behavior disorders.

Physical symptoms of Angelman Syndrome

From a physical point of view, children with Angelman Syndrome usually present the following characteristic (though not necessarily all) features:
  • The size of the head is usually small in proportion to the rest of the body, what is known in medical terms as microcephaly. It occurs in 80% of cases.
  • The mouth is large, wide and separated, teeth and is usually an exaggerated protrusion of the tongue and jaw (prognathism). These changes tend to be more evident from the 12 months of life.
  • Hypopigmentation: the color of hair, skin and eyes presents a clearer hue in comparison with their family of origin, and may suggest the presence of albinism in the most severe cases.
  • Occasionally there may be visual impairments such as strabismus, atrophy of the optic nerve or presence of known as the 'Brushfields 'spots in the iris.

Neurological symptoms of Angelman Syndrome

From a neurological point of view, these children may suffer, among others, the following demonstrations:
  • Alterations of the March with strange postures of the upper extremities which, according to the form, remember to a puppet or a chandelier (hence the name that drew them initially those affected by Angelman Syndrome: 'puppet boys').
  • Abnormal limb movements (trembling or shaking), appearing more frequently in the first months of life. These incoordinados movements hamper the child performing basic tasks as walking, eating or pick up objects with the hands. For this reason, the development of children with Angelman syndrome is slower that in healthy children (for example, begin to sit 12 months of life and to walk around 3-5 years).
  • Seizures of different types that, in some cases, do not respond well to conventional medication. Most of these crises begin from three years of age, while in 25% of cases they may appear before the 12 months of life. The severity of seizures decreases with age, but they persist throughout adulthood. Electroencephalogram (medical test that records the brain bioelectrical activity in different conditions) presents a characteristic pattern in 80% of cases, regardless of the child affected by Angelman Syndrome to any seizure or not. This may allow to make an early diagnosis, especially in the early stages of the disease.
  • Sleep disorders.
  • Communication disorders: oral language tends to be incoherent, without issue in many cases more than two consecutive words. The gestural ability also tends to be impaired. Compression remains something better, in fact, children affected by Angelman syndrome tend to have good memory for faces. These difficulties to communicate make affected children to resort to other types of behaviors to express their emotions and needs, as pulling hair, biting, hitting, or push others. Therefore it is working on other routes of communication learning to improve the quality of life of these patients and help them to communicate as an alternative.
  • Other signs: stiffness, instability, stature, sudden movements or small limbs.

Psychological symptoms of Angelman Syndrome

Psychological characteristics most frequently associated with Angelman Syndrome are:
  • Severe mental retardation, which causes that the people affected by this syndrome do not reach the minimum skills of personal autonomy.
  • Characteristic behavior: people suffering from Angelman syndrome have affective behaviors and happy child's appearance. They have interest in establishing relationships with other people. They are friendly and have good social attitude. Degree of hyperactivity and attention deficit can also be observed. A curious feature of these children is his fascination with water and plastic.
Other alterations that can be found in these children are difficult to suck, swallow and even tendency to spit out food (probably in relation to the uncoordinated movements of the tongue). These alterations in food can trigger problems with weight and growth.
Another curious feature of those affected by Angelman syndrome is the presence of excessive sweating and poor tolerance to heat. Moreover, children with this syndrome have a normal physical and sexual development, although puberty may be delayed in 1-3 years.

Diagnosis of Angelman Syndrome

The diagnosis of Angelman Syndrome may be confirmed by clinical and laboratory findings. It is difficult to do it at the time of birth or in the first months of life, since at that time the problems of development are not very obvious. The age range in which Angelman syndrome is diagnosed normally is between three and seven years of age.
To make the diagnosis there are diagnostic criteria collecting clinical characteristics, development and examinations. The definitive diagnosis is achieved by conducting a genetic study.
  • Clinical criteria: are grouped, according to their frequency of appearance, in:
    • Consistent (100%): delayed psychomotor development, impairment of speech, movement or balance and special behavior disorders.
    • Frequent (80%): delay disproportionate growth of the size of the head, seizures and abnormal electroencephalogram.
    • Associated (20-80%): flat occiput and occipital Groove, strabismus, prognathism, wide-mouth, hypopigmentation of skin and eyes, increased sensitivity to heat, sleep disorders, problems of food, etc.
  • Features of development.
  • Complementary tests:
    • Analysis of blood and urine normal.
    • (Cerebral resonance and computed tomography) imaging unaltered tests.
    • Characteristic electroencephalogram in some cases.
The confirmation of Angelman Syndrome diagnosis is made by a genetic study, making a karyotype (study of the chromosomes) that allows to detect the characteristic anomalies causing this syndrome. Other tests can also be performed as the test of hybridization in situ (FISH) or the test of DNA methylation, allowing to study alterations in chromosome 15.
With the diagnostic criteria and the genetic study gets to diagnose the vast majority of those affected, however, on some occasions (around 20% of cases) a definitive diagnosis is not reached.

Treatment of Angelman Syndrome

There is no curative treatment for Angelman Syndrome, but if a treatment of its symptoms can be performed and, depending on each case, can be offered special support measures. Therefore, treatment of Angelman Syndrome is a multidisciplinary treatment, with individualization according to each case.
From a medical point of view, different alterations associated with Angelman Syndrome such as hyperactivity, epilepsy, disorders of sleep or scoliosis (spine deviation) can be treated:
  • In hyperactivity, some affected can benefit from treatment with methylphenidate.
  • Seizures usually require treatment with anticonvulsant drugs, although it appears that no drug there is more effective than another (importantly, identify in each case). Conducting reviews by the neuropaediatrician is important.
  • For sleep disorders may be helpful melatonin and behavioral therapies, but in more severe cases may be used even to sedatives.
  • Scoliosis physiotherapy, is important to facilitate the child's motor development.
It is also important that treatment encompasses the psychological field. To do this, relaxation techniques (for controlling the excitability and improve care), should work as well as behavior modification therapies (appears to be effective in the correction and modification of behavior and inappropriate behaviours). In addition, should encourage participation in social activities, to enhance relations with the environment as well.
Measures should be taken to enhance perception, motor skills, attention, intelligence, cognition or language. Communication therapies are one of the pillars of the treatment. The speech therapists work both the non-verbal and verbal communication with an emphasis in the latter due to the characteristics of this disease. Educational programs must be flexible and adapt to the needs and abilities of these children.
Finally, if other types of alterations have to be treated in a specific way in each case

What is Cushing's syndrome

A syndrome is a set of signs and symptoms. In Cushing's Syndrome they are caused by an excess of chronic cortisol. Cortisol is a hormone type glucocorticoid produced naturally in the adrenal capsule, an endocrine organ - i.e. it produces hormones - located above both kidneys. Also known as the "stress hormone" cortisol plays very important actions, such as the maintenance of blood glucose levels and the functioning of the nervous and cardiovascular systems. In addition, the cortisol protects autolesivos mechanisms as, for example, responses inflammatory and immune over which can be harmful for the organism.
Excess cortisol is called hypercortisolism or hipercorticismo and may be endogenous, when the cause is in the body, or exogenous, due to natural or synthetic glucocorticoids above the physiological dose.
High doses of corticoids are part of the treatment of leukemias, lymphomas, transplants, etc., due to their anti-inflammatory properties and its ability to curb some immunological responses. Today, steroids are essential for the treatment of many of these diseases, and why his administration is the most frequent cause of (exogenously) Cushing's syndrome.
In adults, the most frequent endogenous is called disease Cushing, which is due to excessive secretion and chronic way of a hormone that stimulates the production of glucocorticoids for the adrenal; This hormone is the adrenocorticotropic or ACTH, which is released into the blood from the pituitary gland, an organ that produces various hormones which, in turn, act in various hormones (endocrine organs)-producing organs. ACTH induces the glucocorticoid and androgen production by the adrenal.
This disease is approximately eight times more common in women than in men, and usually occurs more between 20 and 40 years of age. In more than 90% of the cases of Cushing's disease is detected a benign tumor in the pituitary gland - usually an adenoma-producer of ACTH.
Endogenous Cushing's syndrome is a rare entity: has an incidence of two to four cases per million inhabitants per year; and the most frequent cause, Cushing's disease, has an incidence of 1.2 to 2.4 cases per million inhabitants per year.

Symptoms of Cushing's syndrome

The symptoms and signs of Cushing's syndrome vary with age, sex, and also with the cause, the intensity and the duration of the hipercorticismo. The disease can cause obesity, variations in skin, arterial hypertension, mental disorders, osteoporosis, disorders of glucose metabolism, etc.
Obesity in this syndrome has very special characteristics, since it affects especially the face and trunk. The sick person's face is round (described in the books of medicine as a "Moon face") and Ruddy, and the neck is very thickened (described as "Buffalo neck"). Skin, in general, is thinned, with streaks of purplish red color in the abdomen, hips, armpits, breasts and thighs. Hematomas appear very easily, spontaneously or with minimal trauma. Wounds heal later than normal.
High blood pressure tends to be moderate. Mental disorders such as depression, irritability, anxiety, insomnia, emotional lability, panic and paranoid pictures occur in approximately half of patients.
Disorders of the metabolism of glucose produce diabetes mellitus. Osteoporosis (bone loss) can be very intense, favouring the emergence of fractures, and occurs most often in young patients. Urinary calculi due to an increased elimination of calcium can also produce in the urine. In children there is a delay of growth and maturation of the bones.
Cases with increased secretion of ACTH in the skin takes a dark color. In addition, women do not have menstruation or it is minimal, and if they also have an increase in androgens of adrenal origin occurs Seborrhea, acne and increase the hair on different parts of the body (HIRSUTISM).

Diagnosis of Cushing's syndrome

Exogenous Cushing Syndrome is easy to detect for physicians that are treating a patient with glucocorticoids. In these situations tries to best balance the effects that they have to exercise on the basic problem being treated and side effects, i.e., the Cushing's syndrome that can cause.
The endogenous hipercorticismo, however, requires a study allowing the diagnosis - elevation of cortisol, ACTH or both - and discover the cause. Not always detect an increase in cortisol or ACTH is easy, since they may not be increased at any time. Thus, endogenous cortisol excess is demonstrated by the detection of free urinary cortisol increased in several determinations, and also if it is detected plasmatic cortisol high blood extracted by the morning after the oral administration of dexamethasone (1 mg) at 23:00 of the day before (called fast inhibition test). There is a test similar to the latter in which a greater amount of dexamethasone is administered during two days (weak inhibition test).
Other tests used for the diagnosis of Cushing's syndrome are the determination of cortisol in the blood and saliva at 12 in the night and during sleep; It is normal that during the night, cortisol levels are low, but in patients with this syndrome are higher.
For the detection of ACTH, in the majority of cases is not enough direct determination in blood, on the other hand, is almost always required a releasing hormone CRH or ACTH stimulation test.

Diagnosis of the origin of the hipercorticismo

For the diagnosis of the origin of the hipercorticismo should consider two types of ACTH-dependent and that it is not. In the first case, there is an increase in the hormone ACTH, which may be of pituitary origin or there is also the possibility of ACTH to be produced by a tumor is in a location different from the pituitary gland. In the second case, when the syndrome is not due to an increase in ACTH, cortisol excess is, in general, a producer of the same tumor located in the adrenal gland.
The CRH stimulation test serves to distinguish if the high production of ACTH from the pituitary gland, in which case the response in this test is excessively large, or does not come from the pituitary gland, with a low response. With this test there is no response if Cushing's syndrome of adrenal origin, i.e. without hiperproducción of ACTH. So what is the cause of Cushing's syndrome there is high-dose dexamethasone suppression test.
Depending on the results obtained in the hormone study will use diagnostic methods that ensure the location of the tumor:
To detect a pituitary adenoma - is a benign tumor, the most common pituitary ACTH producing tumor - cranial magnetic resonance imaging will be used.
If the tumor in the resonance - is not sometimes are tiny, even microscopic-, ACTH in the arterial blood next to the pituitary through an arterial catheterization can be measured.
If you suspect that the origin is adrenal, you can see the tumor by computed tomography, magnetic resonance and ultrasound of the adrenal glands.
If you suspect that the origin is a located outside (ectopic tumor) pituitary ACTH producing tumor, is usually a CT scan of the chest - more than half of ectopic tumors are located here - and abdomen; You can also scan, which can detect the tumor in any part of the body and see your extension.

Treatment of Cushing's syndrome

Endogenous Cushing's syndrome is not and continues to evolve it can cause death, usually caused by cardiovascular alterations. On the other hand, patients have high blood pressure, diabetes mellitus of difficult to control, psychiatric disorders, complications of osteoporosis and serious electrolyte disturbances.
The treatment depends on the cause of the syndrome. If it is a Cushing's disease, should completely remove the pituitary tumor. In the majority of cases this is achieved by an operation to remove the tumor through the base of the skull - specifically bone, sphenoid, which is just below the gland pituitary gland - through the nose.
Cushing's disease can return even after ten years, so that periodic checks are recommended.
There is also a drug treatment, which is often used before surgical treatment, to reduce the symptoms of the syndrome. These drugs are - the most widely used - ketoconazole and the metopirone.
Treatment of ectopic ACTH-producing tumors is, whenever possible, the removal. When this is not possible, the pharmacological treatment mentioned above and also octeótrido or lanreotide is used.
Treatment of adrenal tumors is surgical. Most are adenomas - benign tumors - and his removal involves the cure. Adrenal carcinoma has poor prognosis and the best thing is the total removal of the adrenal, also mitotane (an active principle), is used to treat the symptoms, along with chemotherapy. In case of removal of the two adrenal cortisol and fludrocortisone treatment is necessary in life.

What is Klinefelter Syndrome

Also known as 47-XXY syndrome, Klinefelter's syndrome is defined as a chromosomal disorder that affects male sexual development. In 1942, Dr. Harry Klinefelter and colleagues at the Massachusetts General Hospital, in the city of Boston, published a special report on nine men who had the enlargement of breasts, little facial and body hair, small testes, and inability to produce sperm.

What is the cause of Klinefelter's syndrome?

In the 1970s, researchers from around the world tried to identify the cause of this syndrome and karyotype (chromosome map) studies conducted more than 40,000 newborn male. They found that the prevalence of this syndrome is of one case per every 500 to 1,000 newborn babies living males and that children with Klinefelter Syndrome had an extra copy of the X chromosome in each cell, i.e. its karyotype 47, XXY was.
There are also variants of Klinefelter Syndrome that include more than one X chromosome extra or copies extras and both X chromosomes in each cell, as in the so-called case mosaic. These patients often have signs and symptoms more severe than classic Klinefelter Syndrome, as well as affecting male sexual development have problems with learning, distinctive facial features, skeletal abnormalities, coordination of movements, and severe language problems.

Symptoms of Klinefelter Syndrome

These are the most common signs with patients affected by Klinefelter's syndrome:
  • Men with Klinefelter's syndrome typically have very small testicles that are not able to produce testosterone, which is the hormone that directs the male sexual development before birth and during puberty.
  • The decrease in the quantities of testosterone during puberty can produce an increase in size of the mammary glands (gynecomastia), decrease in body hair, beard and, finally, inability to have children, since they do not produce sperm (azoospermia and infertility).
  • Decreased sexual desire (libido).
  • They are also overweight, since they have a tendency to the accumulation of fat especially at the level of the hips.
  • Children and young people who suffer from this syndrome tend to be carving high with respect to the same age.
  • Patients with Klinefelter's syndrome may also have learning problems and difficulties with the development of the language. Also, they tend to be shy, quiet, sensitive and with little ability to establish trials.

Diagnosis of Klinefelter Syndrome

· When the physician has the clinical suspicion that a person has Klinefelter's syndrome, a test called a karyotype in order to obtain a map of the chromosomes of the patient must be requested. The karyotype of a person with Klinefelter Syndrome is usually 47, XXY. Normal male karyotype is 46, XY.

Prenatal diagnosis

· In recent years, many men have been diagnosed with Klinefelter's syndrome before birth, through biopsy of villus sampling, amniocentesis or funiculocentesis. These samples are obtained fetal cells for karyotype determination. None of these procedures are usually used except when there is a family history of genetic defects, or when screening for malformations is performed during the pregnancy is detected a high risk of genetic defects in the fetus.

Is it hereditary Klinefelter Syndrome?

· While the cause of this condition is the presence of an extra copy of the X chromosome, Klinefelter's syndrome does not inherit. This syndrome is usually the result of a random event that occurs during the formation of reproductive cells (eggs and sperm) called meiosis. An error in a reproductive cell division called nondisjunction (when the chromosomes during cell division migrate to a single pole of the cell) leads to an abnormal number of chromosomes. For example, an egg or a sperm can have one or more copies extras of the X chromosome, as a result of the nondisjunction .
· Apparently there are some risk factors that have been associated with these events, such as the advanced maternal age, increasing the risk of emergence of the syndrome. On the other hand, it has been suggested that in more than half of the cases it is the father that provides the extra copy of the X chromosome.
· The mosaic case with a karyotype 46, XY/47, XXY is not hereditary. It occurs as a random event during cell division in the early development of the fetus. As a result, some of the cells of the body have an X chromosome and a chromosome (46, XY), and other cells have an extra copy of the X chromosome (47, XXY).

Prognosis and treatment of Klinefelter's syndrome

Klinefelter Syndrome is a chromosomal problem, there is no treatment for the disease, even if most of the symptoms can be treated.
In general the prognosis of Klinefelter Syndrome is good, provided the patient is under strict medical monitoring, allowing early treatment of any problems that occur. Many men with affected with this syndrome manage to lead a normal and active life.
However, patients with Klinefelter's syndrome have an increased risk for certain diseases, such as: diabetes type 1, lupus, hypothyroidism, male breast cancer, lymphoma non-Hodgkin's, obesity, and osteoporosis. For this reason the doctor can program certain diagnostic tests such as blood glucose, thyroid hormones, breast ultrasound, etc., to detect in time the problems above.
Because of these diseases and their complications, a person with Klinefelter Syndrome may have increased risk of early death.

Use of testosterone

Ideally, males with Klinefelter Syndrome to begin treatment with testosterone as soon as they enter puberty, although those diagnosed in adulthood may also benefit from treatment with this hormone.
A scheme of regular application of injections of testosterone will produce: increase strength and muscle size, and growth of facial and body hair.
In addition to these physical changes, testosterone injections often cause physiological changes. As they begin to develop a more masculine appearance, males with Klinefelter Syndrome often increase their self-esteem. Many become more dynamic and energetic, improve mood and general mood. Something very important, because, as a group, children 47, XXY tend to suffer from depression, mainly because of their school difficulties and adjustment problems with other children of the same age.
Other testosterone benefits include a reduced need for sleep, a greater ability to concentrate and improve the relationships with others.

Treatment of endocrine problems

As for the rest of typical problems associated with this syndrome, they can address follows:
  • Control of body weight and obesity by diet, periodic exercises.
  • If you have high levels of cholesterol or triglycerides in blood you can add some medications such as simvastatin and atorvastatin.
  • If you have high levels of blood sugar or insulin resistance you can use drugs such as metformin or even regular doses of insulin.
  • If you have osteoporosis must consume dairy products rich in calcium and according to medical indication supplements of calcium plus vitamin D (more information about nutrition in osteoporosis).
  • Thyroid problems may require the use of thyroid replacement hormones.
  • If Gynecomastia (breast augmentation) is very pronounced can consider the possibility of reducing cosmetic surgery of the breast, as the breast.

What is the Patau syndrome

Patau syndrome, also called Bartholin-Patau or Trisomy 13 syndrome, is a chromosomal abnormality, in which the patient has an extra copy of chromosome 13. Trisomy 13 is characterized by multiple serious, both anatomic and functional alterations in organs and vital systems. It is for this reason that many of the children who are born with this condition do not survive beyond the first three months of life, and according to the scientific literature around 80% of fetuses affected by this problem do not reach term.
The prevalence of this syndrome is low, one case per each twelve thousand newborns alive, and occurs more in girls than in children, probably because male fetuses with this syndrome survive less than female fetuses.
In history are records of Patau syndrome since 1657, when the medical Danish anatomist Thomas Bartholin made the first description of a case, but it was not until 1960 that his medical geneticist Klaus Patau reported the presence of an additional thirteen chromosome in these patients.

What is the cause of Patau syndrome?

As in other syndromes caused by chromosomal alterations, when the reproductive cell (either the maternal ovum or the paternal sperm) divides an inadequate migration of chromosomes occurs and there is an extra copy of chromosome 13, which may well be present in all cells, in which case it is called Trisomy; or may be present only in some cells and others do not, what is called mosaicism; Finally only a part of the extra chromosome in every cell, can be what is known as a partial Trisomy .
Advanced maternal age is a risk factor for this syndrome. On the other hand, must be taken into account as Patau syndrome not inherited from parents to children.

Patau syndrome symptoms

These are the common more signs that present those affected by Patau syndrome:

Malformations of the nervous system

  • Dilation of the cerebral ventricles.
  • Ruling on the division of the brain into two hemispheres during the embryonic period (holoprosencephaly).
  • Severe mental retardation.
  • Epilepsy.

Head and neck malformations

  • The size of the smaller head than normal (microcephaly).
  • Very small eyes (microphthalmia) or very close to that even they can be fused into one. They may also have a recess in the iris of the eye, which is called a coloboma.
  • Small Chin (micrognathia).
  • Cleft lip or cleft palate.
  • Absence of the nose or nasal malformations.
  • Ears (ears) of low implementation.

Abdominal malformations

  • Umbilical or inguinal hernias.
  • Omphalocele (malformation of the abdominal wall through which the viscera are outside the abdominal cavity, which occur during the embryonic period).
  • Bladder Exstrophy (malformation of the bladder and urethra).
  • Renal Agenesis (one or two kidneys absent at birth).
  • Absence of testes in the scrotum or Undescended testicles.

Cardiac malformations

  • Location of the heart on the right side of the chest instead of the left side which is called dextrocardia.
  • Pathological communications between various cavities of the heart, the ventricles and Atria.
  • Abnormal heart valves.

Malformations in the extremities

  • Presence of extra on hands and feet (polydactyly) fingers.
  • Foot valgus (deviation of the foot away from the midline).
  • Hands in the form of fist (webbing of the fingers).
  • Fold in the Palm of your hands.
  • Decreased muscle tone (hypotonia).

Diagnosis of Patau syndrome

· Patau syndrome can be detected during the embryonic period, either through an obstetric ultrasound, which are often detected at an early stage the different anatomical malformations of fetuses. Also through the karyotype (chromosome map) using fetal cells obtained by biopsy of villus sampling (which are part of the fabric of the placenta), amniocentesis (to obtain amniotic fluid) or funiculocentesis (one of blood vessels in the umbilical cord puncture).
· If the mother has not controlled its pregnancy, the diagnosis can be immediately after birth, because the morphological features of these newly born are well known by paediatricians and neonatologists. Presumptive diagnosis should be confirmed by karyotype of the newly born and various imaging studies such as brain, abdominal ultrasound, echocardiography, CT, which is may rating malformations of different organs and systems typical of this syndrome.

Genetic counseling

· If a partner has conceived a fetus with Trisomy 13 previously and want to try a new pregnancy they should be studied exhaustively by specialists in genetics and reproduction to try and control the possible risk factors, even though the probability of recurrence is low.
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Treatment and prognosis of Patau syndrome

There is no treatment available for this syndrome; the only thing that can be done is to work the complications that may arise early palliative.
Because all malformations described, the prognosis of Patau syndrome-affected children is very bad and the complications begin practically from birth, the severity of these will depend on the organs and systems affected. The main complications are usually:
  • Respiratory problems, such as apnea, by what may require ventilation in a neonatal intensive care unit.
  • Feeding difficulties, are not as able to suck, so they must be fed through a tube nasogastric tube.
  • Seizures, changes in vital signs such as heart rate, blood pressure or heart rate, among others.
If the baby with Patau syndrome can survive these complications hardly reach the year of life.

What is Rett syndrome

Rett syndrome is a disease of the neurological development of genetic cause affecting mainly children and very rarely children. This disease is named after the doctor Austrian Andreas Rett, who describes the cases of 22 girls who had repetitive movements in the hands, in 1966 as "wash hands", accompanied by motor problems and mental retardation.
Often merges with autism, paralysis with delays in development without a source or cerebral clear Rett syndrome.
The cause of Rett syndrome is an alteration (mutation) in the gene MECP2 (methyl-CpG-binding protein 2), located in the locus (position of a gene within a chromosome) q28 of Chromosome X. Through this gene produces a protein (called MeCP2) which is widely distributed at the level of the cell nucleus and is especially abundant in mature neurons of the central nervous system. This protein plays an important role in the regulation of Synapse (communication between neurons) and is essential in the development of the nervous system after the first months of life. There are more than two hundred mutations described in this gene, however is not known exactly how works the abnormal protein that encodes the mutated gene to produce the disease.
Although Rett syndrome is genetic cause, by about ninety-nine percent of the cases the mutation appears in the patient spontaneously during its embryonic development in the womb, therefore it has not inherited it from their parents. In one percent of the remaining families with Rett the defective gene has been transmitted from women carrying the mutation towards their children. Scientists are still trying to understand the process of inheritance in this complicated disease.
In relation to its prevalence, this disease is classified into the Group of rare diseases and occurs in one of every 10,000 newborns live female, being the second most common cause of mental retardation in this sex.
It is usually diagnosed during the first two years of life, it is essential to indicate treatments aimed to improve psychomotor retardation presenting patients, since changes in the normal patterns of social and mental development begins between six and 18 months.
When the mutation appears in newborn male disease is usually very aggressive, because children have a single X chromosome and they die during the first days of life.

Symptoms of Rett syndrome

The symptoms of Rett syndrome usually appear after a period of apparent normal development, which has a duration of approximately six to eighteen months, passed this time is when it starts a period of stagnation or slowdown in the development of the child, are alterations of the March and the characteristic of the washing of handsstereotyped or repetitive movements, which are the most obvious signs of Rett syndrome.
It is important to highlight that this disease is not a disease neurodegenerative, but a disease of the development of the brain, therefore altered all its functions are: the development of cognitive, sensory, motor, emotional and Autonomic (sympathetic and parasympathetic) nervous system. Thus the symptoms are focused in the following areas:
  • Learning (with difficulty remembering facts, understand ideas or solve problems).
  • Language (delay in the acquisition of speech).
  • Mood (children with easy, inconsolable crying, irritability).
  • The movement (apraxia or inability to control movements and loss of muscle tone).
  • Breath (abnormal breathing patterns: apnea, hyperventilation, etc).
  • Cardiovascular functions, specifically altering the conduction of the nerve impulse through the heart cells resulting in disorders of heart rhythm as a slowing of the heart rate (bradycardia) or other arrhythmias.
  • Chewing, swallowing and digestion of food. Alterations in these functions of the gastrointestinal tract occur as a result of the malfunction of the autonomic nervous system that regulates them. This results in difficulty swallowing, bruxism (grinding your teeth involuntarily), involuntary movements of the tongue, constipation, abdominal pain, gastroesophageal reflux or stones in the gallbladder, even to the point that many girls rely on a stomach tube for feeding.
  • Epilepsy: seizures in more than fifty percent of patients with an age of onset ranging from three to five years can be seen. Seizure type more common in these patients are generalized tonic-clonic.
  • Scoliosis or deviation of the spine in a seventy-five per cent of the cases.

Diagnosis of Rett syndrome

The diagnosis of Rett syndrome can be difficult, because it is a disease of low prevalence that may be confused with other more common pathologies affecting the psychomotor development of children. Clinicians must apply for various tests that guide the differential diagnosis, such as:
  • Hemogram, determination of liver proteins in blood (proteinogram), electrolytes, urea, creatinine, enzyme (transaminase), ceruloplasmin (copper carrier)...
  • Hormone tests to assess the thyroid gland.
  • Determination of the karyotype.
  • Tests that assess the physiology of the brain (such as the electroencephalogram), muscles and nerves (such as electromyography), or the conduction velocity of sensory nerve impulses (such as evoked potentials). Evoked potentials measured nerve conduction from some sense organs to the brain. In Rett syndrome, there may be a slowing of this nerve impulse that reaches the brain after an auditory or visual stimulus.
  • Studies of cerebrospinal fluid.
  • Image, such as computed tomography and magnetic resonance studies.
  • Laboratory confirmation test is a genetic test in the patient's blood to detect the presence of the mutation in Chromosome Xin their DNA. This takes place a test known as reaction by polymerase chain (PCR) and direct sequencing of the gene.

Treatment of Rett syndrome

There is no specific treatment for Rett syndrome, patients affected by the disease should be treated by a multidisciplinary team of specialists such as pediatricians, neurologists, physical therapists, therapists of language, psychologists and psychiatrists among others. They must be inserted in educational, social and recreational activities both at home and in their communities. This can facilitate learning and improve to some extent wandering, language, motivation, etc. They are also required physiotherapy treatments and programs to improve the manual activity and communication, to decrease muscle stiffness, to decrease anxiety, etc.
Knowledge of the disease by family members who live with the patient must be a fundamental objective to achieve by health professionals in charge of these cases.
On July 1 of the year 2007 was born Syndrome Rett (IRSF) International Foundation, an organization nonprofit that provides support to patients, families, and researchers to promote knowledge of the pathophysiology of the disease and find an effective treatment against it.
Currently many trials are being conducted in animal models such as mice, in which stop the course of the disease and even reverse its effects on neurological development is achieved. The scientist in charge of such investigations is the Dr. Adrian Bird, who is also Professor of Genetics at the University of Edinburgh; the MECP2 gene at the beginning of the 1990s was discovered in his laboratory.
No medical treatment has shown satisfactory results in the treatment of this syndrome. Some drugs that have been tested to treat Rett syndrome are:
  • L-dopa, which apparently improves the rigidity of the muscles;
  • Naltrexone, an opioid derivative used to treat alterations of the respiratory rhythm, seizures and irritability;
  • Bromocriptine, which can reduce the involuntary movement of the hands;
  • Some essential amino acids such as tryptophan, tyrosine and L-carnitine to increase the synthesis of neurotransmitters by neurons.

Treatment of the complications of Rett syndrome

In any case, the effectiveness of all these treatments is scarce and little lasting, for which treatment is often aimed at treating the complications of the disease. Like this:
  • They may be necessary antiepileptic drugs, including carbamazepine, valproic acid, lamotrigine, or topiramate, preventing seizures.
  • Some patients with severe swallowing problems may require the insertion of a tube into the stomach to provide nutrition.
  • In the case of gastroesophageal reflux, they are necessary antacids or other anti-reflux medications.
  • Are also often recommend diets highly caloric, to improve nutrition, and preventive treatment of osteoporosis with supplements of calcium and vitamin D.
  • Also have to treat constipation, possible sleep disorders, etc.
  • Sometimes surgery is needed to correct scoliosis or gastroesophageal reflux.
  • It is very important to identify possible heart rhythm disorders which would endanger the life of the patient. Sometimes antiarrhythmic drugs can be given to reduce the risk of arrhythmias. It should bear in mind that some medications increase the risk of arrhythmias in these patients. It is therefore advisable to consult your doctor before any drug to these patients.

What is Turner syndrome

Turner syndrome It is defined as a genetic disorder caused by an alteration (by total or partial absence) of the X chromosome. Humans have 46 chromosomes, which are small structures shaped containing genetic information or DNA that are present in the nucleus of all the plant and animal cells. Of these 46 chromosomes, there are two that determine the sex of individuals: the X and the and. Women have two chromosomes X, one inherited from the father and the other from the mother. For their part, men have an X chromosome inherited from the mother and one chromosome and inherited from the father.
Therefore, this genetic disease only affects girls, since children, having only one X chromosome, the total or partial absence of the same would be incompatible with life.
Exact cause why this chromosomal disorder occurs is not known, although they are running two possibilities. On the one hand, it could be due to an error in the division of sex cells (meiosis), occurred at the time of forming the egg or sperm, making that one of the two does not carry the X chromosome. On the other hand, also the option that chromosome loss occurs later, in the division of the already fertilized (mitosis), immediately Shuffle after conception. The frequency with which this syndrome occurs in the population is 1 between 2,500 new female live births.
Turner syndrome named after Dr. Henry Turner, doctor who described it for the first time in 1938. This disorder is also known as syndrome 45, X; Bonnevie-Ulrich syndrome; Morgagni-Turner-Albright syndrome or Monosomy X, among many others.

Symptoms of Turner syndrome

These are the typical clinical features of a case of a patient with Turner syndrome:
  • Stature, generally less than 1.60 meters.
  • Defective formation of ovaries and internal female organs, as well as absence of ovules (gonadal dysgenesis and infertility).
  • Child appearance of the external genitalia and sometimes malformations in them.
  • Shield-shaped chest.
  • Cardiac and renal malformations.
  • Flabby folds in the back of the neck, which is known as "webbed neck" or pterigium colli.
  • Alteration in the alignment of the bones of the forearm. What produces a cube valgus or displacement of the forearm out.
  • Low implantation of hair.
  • Increase in volume or swelling of hands and feet.

Diagnosis of Turner syndrome

Most suspected cases of Turner syndrome is diagnosed by pediatricians, because they know the clinical features of these patients. What startles most is the stature, the increase in volume of hands and feet, webbed neck, hairline line low at the neck and the cubitus valgus (the displacement of the forearm out).
The most important diagnostic test to be performed at the suspicion of a case of Turner syndrome is the karyotype, which is defined as a pattern of the chromosomes of a species. To make this test a sample of the patient's blood is taken and grown in the laboratory. About 50% of patients with Turner syndrome have the pattern 45, XO , that lack them an X chromosome. Later, more frequent findings are partial losses of pieces of chromosomes (deletions), or a full arm of chromosome X or mixture of several of them in different cells (what is known as mosaic).
When he has already confirmed the diagnosis of Turner syndrome, should be more in-depth molecular genetic studies to determine if the patient has genes of chromosome and, when it is present there is an increased risk (of 15-25%) develop tumors as gonadoblastoma or the dysgerminoma in the male pseudogandula, i.e. what would have been the testicles , surgical excision is recommended.
Other complementary tests for the diagnosis of Turner syndrome are the x-ray of wrist to calculate bone age a cardiological assessment by echocardiography to detect malformations, a hearing test, and an abdominal and pelvic ultrasound to evaluate renal malformations and reproductive organs.

Prenatal diagnosis

It occurs before birth by the analysis of fetal cells, which can be achieved by conducting various tests:
  • Chorionic biopsy: in this technique, the fetal cells, from the villus sampling which originate the placenta, are obtained by cell culture. This is done between the ninth and the twelfth week of pregnancy.
  • Amniocentesis - consisting of a puncture through the wall of the uterus to remove amniotic fluid (which float fetal cells) - can be performed between weeks 14 and 16 of pregnancy.
  • And finally, with the funiculocentesis or direct puncture of the umbilical cord, to obtain blood from the fetus. It can be from the 20th week of gestation.
An ultrasound study it can be suspected that the fetus is affected of Turner syndrome; the most common abnormalities are cystic hygroma (filled cavity of lymphatic fluid) in the neck of the fetus, in 88% of cases; hydrops (abnormal accumulation of fluid), 80%; short femur, in 59% of the patients; malformations in the heart, at 48%; and brachycephaly (flattening of the bones of the skull), 32% of those affected.

Treatment of Turner's syndrome

Patients with Turner's Syndrome should be evaluated and treated regularly by a multidisciplinary group composed of various specialists: pediatrician, surgeon, nephrologist, cardiologist, psychologist, nutritionist... The most relevant aspects are covered in the following way:
  • The stature, one of the major clinical problems of Turner syndrome, is treated with growth hormone (while the patients produce this hormone). This hormone has been developed by genetic engineering and is equal to the growth hormone that we synthesize in our body. It is often recommended the daily application of a subcutaneous injection, you must start these injections from four years of life. If not this hormone is given the final size in patients with Turner syndrome can be up to 20 cm less than that of the rest of the female population, but if growth hormone is administered properly this difference it can be reduced to only five or six centimeters less. There are other treatments that can be applied together with growth hormone which consists of the surgical limb lengthening or bone lengthening. The natural evolution of the size in patients with Turner syndrome have a typical pattern:
    • Prenatal growth (inside the womb) phase: occurs late growth so that at birth have a size that is two to three centimeters less than the of the other newly born female.
    • Newborn stage and first year of life: during this stage is still delaying its growth in relation to the size by which never reach the percentile on the growth charts of development for their age and sex. The first year they have about 10 centimeters less than the rest of the girls.
    • Preschool and school stage: maintain the situation of growth retardation.
    • Stage preadolescence and adolescence: arriving 12 years approximately, the size of these girls is below the average and during the development stage there is the typical lug, since they do not produce hormones that are needed to make it happen.
    • Young adult stage: despite being with a stature that the rest of the girls, the growth process stays active longer and this happens for a delay in the closing of ossification points, this results in patients with Turner syndrome can continue won until the age of 19 to 20 cm approximately.
  • In relation to the problems of development must administer treatment with estrogen between 13 and 14 years to make happen the menarche (onset of menstruation), for the development of secondary sex characteristics, in order to reduce the risk of osteoporosis and reduce the risk of vascular disease. Estrogens may be administered through pills, intradermal implant patches in skin... When menstruation occurs (approximately two years later) progestins are added to treatment, making this cyclic. Despite this therapy, women with Turner syndrome usually do not become pregnant spontaneously, with subsequent infertility, however can have children through the techniques of fertilization in vitro (embryo transfer) with the same ease as another woman.
  • The stature and the failure in the ovaries are risk factors for osteoporosis, why must ensure a good supply of calcium and vitamin D.
  • If the patient presents many alterations in face and neck the possibility of plastic surgery should be discussed to attenuate these traits.
  • Weight and diet must be monitored to reduce the risk of obesity and associated diabetes, if you arrive to occur can be treated with oral hypoglycaemic.

What is Williams syndrome

Williams-Beuren syndrome or Williams syndrome is a rare disease of genetic cause that is characterized by alterations in neural development and typical facial features resembling a Pixie .
This disease was first described in 1961 by Dr. Joseph Williams, a specialist in cardiology and originally from New Zealand, who along with his team described four cases of pediatric patients with narrowing of the aortic heart valve, mental retardation , and certain facial features common as wide front, spaced eyes, thick lips and flared nose.
The prevalence of this disease according to the scientific literature has increased considerably in the last twenty years, through a case every twenty thousand newborns live to present reports talking of one case per each eight thousand newborns alive. Because basically that now medical paediatricians and neonatologists have one much greater of these genetic-based diseases knowledge, whose diagnosis has improved since the discovery of the human genome and the application of new technologies of amplification and sequencing of DNA in molecular genetics laboratories.
Williams syndrome prognosis is variable and depends on the severity of the anomalies and the degree of mental retardation that patient. Some affected reach adulthood and are able to live independently, complete basic school or even high school or vocational training. Others live in supervised homes or mostly with a caregiver.
Parents can increase the chances that your child is able to live independently with the early teaching of skills self-help and early insertion into individualized educational programs designed to improve cognitive development and correct the negative personality traits.

Why does Williams syndrome?

Williams syndrome patients have a deletion (type of mutation in the genes or genetic material is lost) of approximately a 26 genes contiguous along the long arm of chromosome 7, specifically in the chromosomal region 7q11.23. Among these genes which are lost is elastin (ELN)gene, which has as a consequence that this protein does not occur in sufficient quantities.
It elastin is a protein that is found in the connective tissue, providing the ability to give for example skin and blood vessels (arteries primarily). Therefore, those affected by Williams syndrome have only one (instead of two) the elastin gene, which causes the common cardiac and vascular diseases in these patients.

Symptoms of Williams syndrome

The characteristic signs of the patient affected by Williams syndrome are as follows:

Cardiovascular alterations

  • Narrowing of the artery aorta immediately above the aortic valve (what is known as supravalvular aortic stenosis), which can range from mild to severe and that can cause heart failure.
  • Narrowing (stenosis) of the renal arteries, resulting in increased blood pressure.
  • Narrowing (stenosis) of the coronary arteries responsible for bringing blood to the heart, which can lead to sudden death.
  • High blood pressure.

Gastrointestinal disorders

  • Difficulty sucking from the moment of birth.
  • Difficulty swallowing food.
  • Hiatus hernia, recurrent vomiting and gastroesophageal reflux.
  • Slowness in the Peristaltic movements of the bowel causing constipation tendency.
  • Chronic abdominal pain and cramping type (like cramping).
  • Abdominal pain of repetition by stenosis of the arteries that carry blood to the gut (mesenteric arteries).

Alterations of the nervous system

  • Mental retardation, whose severity is variable grade.
  • Attention deficit and hyperactivity.
  • Decreased muscle tone.
  • Disability for viso-spatial orientation, they can observe a full object, recognize it and call it by name, but they are unable to do the same if it's objects composed of several parts.
  • Difficulty in coordination fine motor movements such as drawing and writing.
  • Gross motor difficulty problems up and down stairs.
  • Social disinhibition and verbosity (talk a lot and very fast).

Facial alterations

  • Cheeky dwarf's nose and flattened nasal bridge.
  • Wide mouth and thick lips.
  • Groove naso labial and epicanthal folds (crease internal of the upper eyelid) pronounced.
  • Teeth with small enamel, incomplete or spaced teeth.

Other features

  • Small genitalia.
  • Growth retardation, problems to gain weight and height.
  • Skin with aged appearance.
  • Hoarse voice tone.
  • High levels of calcium in the blood (hypercalcemia).
  • Strabismus and hypermetropia (difficulty seeing close objects).
  • Otitis media, to repeat.
  • Easy to learn the language.
  • Super auditory memory and special interest music.
  • They tend to be left-handed and used the left eye.

Diagnosis of Williams syndrome

· Presumption of Williams syndrome diagnosis begins from the pregnancy, if the mother is made the regular prenatal checks, including obstetric ultrasonography, renal arteries, heart and nervous system malformations tests tend to be obvious and allow medical Sonographer to identify the existence of Williams syndrome in the fetus studied.
· Immediately after birth, the diagnosis of Williams syndrome is confirmed by the physical characteristics of the newly born and testing as the cardiac ultrasound (echocardiography), brain ultrasound and abdomino-pelvic ultrasound.
· The diagnosis by molecular genetics is made from a patient's blood sample. Once extracted DNA two techniques can be used to assess chromosome 7 and the deletion (type of mutation in the genes or genetic material is lost) the elastin gene: analysis of micro-array (biochip or chip of microscopic fragments of DNA attached to a solid surface that allows to evaluate multiple genes at once) or the test of fluorescent hybridization in situ (FISH) , a chromosomal analysis technique that uses a DNA probe labeled with a fluorescent particle. So the DNA is subjected to a process of denaturation, i.e. separation of the two strands. Subsequently add the labeled probe, which will be joined by complementarity to the specific site within the DNA molecule, thus detecting anomaly that they are looking for. It then undergoes a process of hybridization to again join the two strands of DNA. Finally the sample is observed in a special microscope that allows to detect the fluorescence emitted by the probe if it has joined with the target site.

Treatment of Williams syndrome

There is currently no specific treatment for Williams syndrome. Patients with this pathology should be evaluated by a group of experts made up of pediatricians, neurologists, cardiologists, gastroenterologists, speech therapists, physical therapists...
Based on the clinicos-radiologicos findings indicate specific for each symptom treatments that will be individualized for each patient depending on the severity of the clinical manifestations of the syndrome that present.
For example:
  • If you have high blood pressure you will receive drugs anti-hypertensive.
  • If you have cardiac rhythm problems they will prescribe them anti-arrhythmia drugs.
  • For reflux gastro-oesophageal give them drugs such as domperidone, gastric protectors (omeprazole, esomeprazole) and changes in positions to sleep as the elevation of the head of the bed.
  • Exercises conducted by physiotherapists to improve muscle tone can be indicated.
  • From the surgical point of view they can be necessary surgeries to correct heart problems as the supra-valvular aortic stenosis, stenosis of the renal arteries or hiatus hernia.
  • Finally, they must be evaluated by a dentist to treat oral problems.
Health personnel consisting of doctors, nurses, social workers, psychologists, etc., should be given to family members and patients all the necessary information for the proper handling of the various alterations present in this syndrome, not only at home, but also in school and in any social environment.

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