Williams Syndrome

Williams syndrome (Williams-Boyren, WS) is a genetic disease characterized by distinctive external signs, a violation of cognitive development of mild and moderate severity, the presence of learning difficulties, cardiovascular anomalies (local or diffuse stenosis of middle or large caliber arteries) and idiopathic hypercalcemia .

Often children with such a diagnosis have astonishing oratorical abilities, great successes in musical art, and have a high level of empathy.

Epidemiology

Williams syndrome occurs at a frequency of 1: 10,000, equally in men and women. In most cases it is sporadic.

[1], [2], [3],

Causes of the williams syndrome

The causes of Williams syndrome have not been fully understood yet, but it is precisely known that in this disease the pair set of chromosomes is preserved in a full-fledged form.

The disorder manifests itself at the genetic level - a part of the chromosome from the 7th pair is lost, because of what this missing area is not transmitted at the time of conception. Because of this, the child develops characteristic Williams syndrome symptoms - each of the genes has its own "specialization", so in the absence of any of them, specific external and internal changes occur.

Since pathology usually occurs spontaneously (due to a chromosomal mutation in conception), it can be concluded that the nature of the disease is congenital, not hereditary. Only in rare cases the disease is hereditary - when at least one of the parents has Williams syndrome.

Such genetic anomalies usually arise as a result of the negative impact on the body of the child's parents - a "harmful" profession, a bad ecology in the place of residence of future fathers and mothers, etc. But such gene mutations can also appear spontaneously, for no apparent reason.

[4]

Pathogenesis

Virtually all cases of Williams syndrome have a haploinsufficiency (i.e., loss of 1 of 2 copies) due to a deletion in the 7 chromosome, in the range of 7q11.23, with the absence of the ELN gene responsible for the synthesis of elastin. The size of the deletion can vary.

Williams syndrome is caused not only by the haploinsufficientness of elastin, but also by the removal of a region that covers more than 28 genes and is therefore considered a syndrome of deletion of adjacent genes. Hypopoiesis elastin leads to the development of cardiovascular pathologies (including nadklapannogo aortal stenosis), pathology of connective and dysmorphology of the face.

Other genes in the deletion region, such as LIMK1, GTF1IRD1, GTF2IRD2, GTF2I, NCF1, STX1A, BAZ1B, clip2, TFII-1, LIMK1 and several others affect the cognitive profile, hypercalcemia, carbohydrate metabolism and hypertension disorders.

[5], [6], [7], [8], [9], [10]

Symptoms of the williams syndrome

Children with this syndrome have special facial features that look like an elf. The first to describe this disease in 1961 was the New Zealand children's cardiologist J. Williams, who studied the cardiovascular system of patients who had a delay in mental development and characteristic manifestations in appearance.

Unlike other genetic disorders, children with Williams syndrome tend to be social, friendly and cute. Parents often say that they do not notice any deviations in the mental development of their children.

But there is another side to the coin. Many children have life-threatening cardiovascular diseases. Children with WS often require expensive and constant medical care and early psychological correction (for example, speech training or occupational therapy) that can not be covered by insurance or public funding.

Many adults with this diagnosis work as volunteers or employees.

In the school period, children often experience strong isolation, which can lead to the development of depression. They are extremely sociable and have a normal need to communicate with others, but often can not understand the nuances of social communication.

The face of an unusual form, a delay in mental development, as well as serious physical disabilities are the main symptoms of Williams syndrome. Among them are heart defects, flat feet or clubfoot, high elasticity of the joints, problems with the musculoskeletal system. Often an incorrect bite is formed (as the teeth of these children are cut rather late). In addition, teeth are small, widely spaced, irregularly shaped, often affected by tooth decay.

In the first 2 years of life sick children are very weak - they eat badly, they have a strong constant thirst, they often suffer from constipation, which is replaced by diarrhea, and also from vomiting. Growing up, children acquire new distinctive features in appearance - an elongated neck, a narrow sternum, a low waist position.

If in infancy these children strongly lag behind their peers in height and weight, then, becoming older, they on the contrary start to suffer from excess weight. Often, with Williams syndrome, there are problems with metabolism - elevated levels of calcium and cholesterol in the blood.

Diseases of the heart and blood vessels

Most people with Williams syndrome have cardiac pathologies (onclaviated aortic stenosis) and blood vessels (pulmonary artery stenosis, descending aorta and intracranial arteries) of varying severity. Stenosis of the renal artery in 50% of cases leads to the development of hypertension.

[11], [12]

Hypercalcemia (elevated levels of calcium in the blood)

Some children with WS have an elevated level of calcium in the blood. The frequency and cause of this pathology are unknown. Hypercalcemia is a common cause of irritability and "colic" in childhood.

In most cases, hypercalcemia passes by itself as a child without any treatment, but sometimes it persists throughout life.

Low birth weight / slow weight gain

Most children with Williams syndrome have a lower birth weight than healthy peers. A slow increase in weight is also characteristic, especially during the first few years of life.

Feeding problems

Many young children have problems in the process of breastfeeding. They are associated with low muscle tone, pronounced emetic reflex, poor sucking / swallowing, etc.

[13], [14], [15]

Gastrointestinal diseases

Often find reflux gastritis, chronic constipation and diverticulitis of the sigmoid colon.

Endocrine pathology

Adults with Williams syndrome are more likely to suffer from obesity, a violation of glucose tolerance and diabetes mellitus compared to healthy people. Underdevelopment of the thyroid gland with subclinical hypothyroidism is also more common

[16]

Kidney anomalies

Sometimes there are abnormalities in the structure of the kidneys with a violation of their functional ability. Often develops kidney stone disease, diverticula of the bladder.

Hernias

Inguinal and umbilical hernias are more common in Williams syndrome than in the general population.

Hyperacusis (sensitive hearing)

Children with this diagnosis have a more sensitive hearing than other healthy children.

Musculoskeletal system

Small children often have low muscle tone and joint instability. When they grow older, joint stiffness (contracture) may develop.

Excessive friendliness (sociality)

People with Williams syndrome are very nice. They have excellent oratorical abilities and are very polite. They are usually afraid of strangers, and prefer to communicate with adults.

[17], [18]

Delay in mental development, learning ability and attention deficit disorder

Most people with WS have learning disabilities and cognitive impairment.

More than 50% of children with Williams syndrome have attention deficit disorders (ADD or ADHD), and about 50% have phobias, for example, fear of loud noises.

By the age of 30, most people with WS suffer from diabetes mellitus or have prediabetes, mild or moderate sensorineural hearing loss (a form of deafness due to impairment of the auditory nerve function).

[19], [20]

First signs

When the child recognizes the symptoms of Williams syndrome, parents, in addition to external manifestations, need to pay attention to how it develops from an early age. Sick children have a weakened body, and also lag behind peers in development, both mentally and physically.

The physical development of sick children is normalized by the 3rd year, but in the speech deviations begin. But parents are not always able to identify the problem, since the baby is very sociable and active at the same time. Also among the signs pointing at Williams syndrome - the timbre of the voice, hoarse and low.

Talking children with this disease begin quite late - it turned out that they speak the first words only in 2-3 years, and they can only pronounce whole phrases for 4-5 years. The syndrome also has problems with visual coordination and motor skills.

The movements of these children are impetuous and rather awkward, it is difficult for them to master even the simplest skills, they are unable to take care of themselves. But while they are very interested in music and show good musical ability.

[21]

The elf's face with Williams syndrome

People who suffer from Williams syndrome have special facial features that look like the elf's face:

• Low position of eyes, swollen eyelids (this is most noticeable when laughing);
• Mouth large in size with full lips and irregularly formed bite;
• Disproportionately wide forehead;
• Full cheeks;
• The nape is convex;
• Flat nose, nose itself small and turned up, nose tip blunt and rounded;
• A slightly pointed chin;
• The ears are quite low;
• Eyes blue or green, can have noticeable "star" or white lacy patterns on their iris. The facial features become more obvious with age.

Williams-Campbell Syndrome

The so-called Williams-Campbell syndrome is called pathology, which arises from congenital inferior development of the elastic and cartilaginous tissues in the distal part of the bronchi (2-3 / 6-8 divisions). The incomplete structure of the bronchial wall causes their hypotonic dyskinesia - they expand sharply when the inspiration is performed and decrease during exhalation. Williams and Campbell in I960 described the manifestation of generalized bronchiectasis in 5 children (the disruption was due to the congenital inferior development of the bronchial framework).

Diagnosis of the syndrome can be at an early age - the disease manifests itself in the form of chronic obstructive bronchitis. Among the main signs - stridoroznoe breath, regular wet cough, the appearance of dyspnea with small physical exercises, a weak voice.

Complications and consequences

In Williams syndrome, the child has an elevated level of calcium in the blood, which can be expressed in the development of certain complications. Arterial hypertension often develops with the development of chronic heart failure.

[22], [23], [24], [25], [26], [27], [28]

Diagnostics of the williams syndrome

The diagnosis of Williams syndrome is primarily determined on the basis of chromosome analysis. But, since some simple anomalies can not be determined by simple anomalies, special genetic tests are carried out during the diagnosis, which can confirm that a certain part of one chromosome of the 7th pair is absent. 

Prenatal screening can reveal signs of a polycystic dysplastic kidney, congenital heart disease, increased fetal occipital transparency, and a decreased level of alpha-fetoprotein (MSAFP) in the blood of the mother.

[29], [30]

Analyzes

When diagnosing Williams syndrome, the following tests are performed:

• FISH-test chromosome parts to confirm the diagnosis;
• Blood sampling for clarifying the level of creatinine;
• Urine examination;
• Analysis of calcium levels in the blood serum, as well as determining the ratio of creatinine and calcium in the urine.

[31], [32], [33]

Instrumental diagnostics

With Williams syndrome the following instrumental procedures are carried out:

• Cardiodiagnostics is a complete clinical examination of a cardiologist, specializing in childhood diseases. Among the procedures - measurement of blood pressure in the hands and feet, as well as an electrocardiogram.
• Diagnosis of the urogenital system - ultrasound of the kidney and ureter, as well as the study of the functional activity of the kidneys.

Differential diagnosis

With Williams syndrome, phenotypic manifestations of Noonan syndrome can be observed .

[34], [35], [36], [37]

Treatment of the williams syndrome

Since Williams syndrome is a genetic pathology, modern medicine is not yet capable of curing it. There are only supporting general recommendations:

• Eliminate the child from additional use of vitamin D, as well as calcium;
• If there is an increased level of calcium, you should try to reduce it;
• With the narrowing of blood vessels (severe form), surgical treatment can be prescribed;
• Physiotherapy exercises to improve the mobility of joints;
• Strengthened course of psychological and pedagogical development;
• Symptomatic therapy.

People with this diagnosis require regular monitoring of the cardiovascular system in order to avoid the development of hypertension and heart failure.

Prevention

Preventative methods of therapy for children with Williams syndrome.

Under the age of 1 year:

• Closely monitor the risk of inflammation of the middle ear;
• When feeding, to cope with difficulties in the transition to solid food;
• Refuse from multivitamin medicines, in which there is vitamin D.

At the age of 1-5 years:

• Follow the diet;
• If necessary, take courses of therapy: speech therapist, exercise therapy, sensory integration;
• Prevent the possibility of constipation;
• If a child has an unreasonable increase in temperature, you need to check it for infection in the urinary tract.

At the age of 5-12 years:

• The correct diet, together with constant physical activity (children with Williams syndrome in early adolescence often suffer from excess weight);
• Therapy aimed at reducing the anxiety of the child (relaxation techniques, advice from a psychologist, treatment with medications).

At the age of 12-18:

• Discuss with the teenager his illness, and also send to a special support group;
• Assist in gaining independence;
• Encourage regular exercise, constant activity and movement;
• Encourage regular visits to doctors to check the gastrointestinal tract and urinary tract;
• Observe the mental health of the adolescent, tracking possible deviations.

[38], [39], [40], [41], [42]

Forecast

Although with age, children with Williams syndrome are increasingly lagging behind their peers in intellectual development, thanks to their ability to listen, as well as complaisance and sociability, the prognosis for improving their mental state is favorable. In the process of teaching such children, one must take into account their spontaneity and excessive gaiety, as well as the foolish mood - therefore, classes should be conducted in a relaxed atmosphere. Also you need to remove from the room all the extra items that can distract the baby. Children with Williams syndrome should communicate with healthy peers - this has a favorable effect on their further development.

Lifespan

People with Williams syndrome have a shorter life expectancy than others.

Cardiovascular diseases (coronary insufficiency) are the main cause of early death in Williams syndrome.

Most specialists associate with an increased level of calcium - because of this at an early age, calcification of the arteries and muscles of the heart develops. In 75% of the patients, the augmentation of the aorta is supra-valued, sometimes in such cases surgical intervention is necessary. Since people with such a syndrome are highly susceptible to the development of cardiovascular diseases, it is recommended that they be examined every year for preventive purposes.

[43]

Disability

Although Williams syndrome is a congenital genetic disorder, it is not the geneticist who directs the disability of such children, but the psychiatrist. This is due to the fact that a child with a genetic defect has mental retardation, which only psychiatrists can diagnose. The normal functioning and vital activity of such a person is hampered precisely by the delay in mental development, on the basis of which he is appropriated a disability.

[44], [45], [46], [47]