Sotos syndrome in children: what is it, symptoms, photos, treatment, prognosis

What is Sotos Syndrome?

Sotos syndrome (or cerebral gigantism syndrome) Is a genetic disorder, described in 1964, characterized by overgrowth before and after birth, large elongated (dolichocephalic) head, characteristic facial features, and non-progressive neurological disorder with mental backwardness.

Signs and symptoms

The main clinical sign is prenatal and postpartum overgrowth. The growth rate is especially high in the first 3-4 years of life, and then continues at a normal rate, but at high percentiles. In childhood, the average height is usually 2-3 years higher than that of their peers. Weight usually corresponds to height, and bone age in childhood increases by an average of 2–4 years compared with chronological age. An adult is usually taller than the average height of normal men or women. Some sufferers become overgrown; Men are known to be 193 to 203 cm (6'4 to 6'8 '') and women up to 188 cm (6'2 '').

The most common craniofacial anomalies are:

• protruding forehead and receding hairline on the forehead in 96% of patients;
• wide-set eyes (hypertelorism);
• tilt of the eyelids and folds downward (palpebral features);
• high narrow sky;
• a pointy chin;
• long narrow face and head shape (see. photo above), resembling an inverted pear (dolichocephaly).

Typical facial features are most prominent in childhood. As the child grows older, the chin becomes more prominent and square. In adults, the craniofacial features are less pronounced, but the chin is visible, and the dolchocephalic and receding hairline (frontal ridges) is preserved.

Symptoms from the central nervous system are not uncommon. Delay in reaching milestones, walking, speaking and, in particular, speaking, almost always present, clumsiness is often observed (60 to 80%), as well as low muscle tone (hypotension) and weakness of the joints. Mental retardation is present in 80-85% of patients with an average IQ (intelligence quotient) of 72 and a range of 40 to borderline mild mental retardation. 15 to 20% may have normal intelligence. Epilepsy may occur in 30% of victims. Some brain abnormalities (enlarged ventricles) may appear.

People with Sotos syndrome can also experience behavioral problems at any age, which can make it difficult for them to develop relationships with others.

In newborns, it is often observed jaundice, feeding difficulties and low muscle tone (hypotension). Heart defects are present in about 8-35% of children with Sotos syndrome, but are usually not serious. Disorders in the reproductive and / or urinary systems occur in about 20% of patients. Other abnormalities associated with Sotos syndrome include conductive hearing loss, which may be associated with increased frequency of upper respiratory tract infections, eye abnormalities such as strabismus, and skeletal problems. Curved spine (scoliosis) occurs in about 40% of patients, but is usually not severe enough to require fixation or surgery. Premature teething occurs between 60 and 80%. About 2.2-3.9% of patients develop tumors, including sacrococcygeal teratoma, neuroblastoma, presacral ganglioma and acute lymphoblastic leukemia.

Sick infants and children are usually delayed in reaching certain developmental milestones (eg, sitting, crawling, walking, etc.). They cannot start walking until about 15-17 months. Sick children may also have difficulty performing certain tasks that require coordination (for example, cycling sports), fine motor skills (such as the ability to grasp small objects), and may exhibit unusual clumsiness. Children with this disorder usually have a delay in acquiring language skills. In many cases, sick children may not speak until about two to three years of age.

Causes

Gene mutations NSD1 are the main cause of Sotos syndrome, accounting for up to 90 percent of cases. No other genetic causes of this condition have been identified.

Gene NSD1 provides instructions for making a protein that functions as histone methyltransferase. Histone methyltransferases are enzymes that modify structural proteins called histones that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases regulate the activity of certain genes and can turn them on and off as necessity. The NSD1 protein controls the activity of genes involved in normal growth and development, although most of these genes have not been identified.

Genetic changes involving a gene NSD1 do not allow one copy of a gene to produce any functional protein. Research shows that a decreased amount of NSD1 protein disrupts the normal activity of genes involved in growth and development. However, it remains unclear exactly how a lack of this protein during development leads to overgrowth, learning disabilities, and other signs of Sotos syndrome.

Most people with Sotos syndrome have a mutation NSD1 is the result of a new mutation not inherited from parents. When parents do not suffer from this condition, the risk of having another child with the syndrome is very low (<1%).

Affected populations

Sotos syndrome affects men and women in equal numbers, occurs in all ethnic groups and has been found throughout the world. This disease occurs in about 1 in 14,000 live births.

Symptomatic disorders

Symptoms of the following conditions may be similar to those of Sotos syndrome. Comparisons can be useful for differential diagnosis. Confirmation of the presence of any of the syndromes can be obtained through genetic testing.

• Weaver's Syndromealso known as Weaver-Smith syndrome, is an extremely rare disease characterized by accelerated growth. Patients have a special facial appearance similar to Sotos syndrome, in which a high, wide forehead is often present, but the face usually round (not elongated) with widely spaced eyes (ocular hypertelorism) and an abnormally small jaw. Children often have increased muscle tone (hypertonicity) and joint problems. It is now known that the cause is a mutation in the gene EXH2.
• Beckwith-Wiedemann syndrome - a rare hereditary disease characterized by excessive growth, an abnormally large tongue (macroglossia), abnormal folds in the earlobes, protrusion of a part of the intestine through an abnormal opening in the abdominal muscle the wall near the umbilical cord (omphalocele) and abnormal enlargement of certain abdominal organs (visceromegaly), such as liver, kidneys and / or pancreas, and hypoglycemia (low blood glucose) at an early age. Most people with Beckwith-Wiedemann syndrome have an abnormality in one of several genes located on chromosome number 11. Molecular genetic testing can help select the right treatment for these patients.
• Simpson dysmorphia syndrome, also known as Simpson-Golabi-Bemel syndrome, is an X-linked recessive genetic disorder characterized by overgrowth before and after birth, a special appearance that differs from Sotos syndrome, extra fingers and toes, additional nipples, separation of the muscles of the abdominal wall (diastasis of the rectus abdominis muscles) and skeletal abnormalities in which the sternum pressed inward. The syndrome is the result of abnormalities (mutations or microdeletions) in one of two genes on the X chromosome.
• Fragile X syndrome - a genetic disorder caused by an abnormality in the gene of the X chromosome, with more serious symptoms in men and characterized by mental retardation, speech delay, behavioral problems, autism or autistic behavior (including poor eye contact and hand clapping), enlargement of the external genitals (macro-orchism), large or protruding ears, hyperactivity, delayed motor development and / or poor sensory skills. Patients may also have an abnormally increased growth rate prior to puberty. Molecular genetic testing can distinguish fragile X syndrome from Sotos syndrome.

Diagnostics

There is no biochemical marker of the disease. Diagnosis is clinical. The most common manifestations are craniofacial changes, overgrowth, and developmental delay. The diagnosis of a patient with a typical craniofacial configuration and overgrowth can be put first. The craniofacial configuration is the most typical and rarely (~ 1%) is absent. Ten percent of children and adolescents may be below +2 standard deviations in height, and 10 or 15% of patients may not be developmentally delayed. Older bone age may be present in 76-86% of patients and is useful for diagnosis but is not specific. Brain abnormalities are present in 60-80% of patients, such as communication hydrocephalus and others, but are not diagnostic.

The diagnosis can be confirmed by DNA studies using FISH (fluorescence in situ hybridization) analysis to detect microdeletions or MLPA (Multiplex Ligate Dependent Probe Amplification), a simple and reliable method for detecting chromosome 5q35 microdeletions and partial deletions gene NSD1, which account for approximately 10-15% of cases in western populations. DNA analysis by genome sequencing can identify specific gene mutations NSD1.

Standard treatments

Treatment for Sotos syndrome is aimed at eliminating specific symptoms that appear in each person. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, pediatric endocrinologists, geneticists, neurologists, surgeons, speech therapists, specialists who diagnose and treat diseases of the skeleton (orthopedists), doctors who diagnose and treating eye diseases (ophthalmologists), physiotherapists and / or other healthcare professionals may need systematic and comprehensive planning of patient care child.

If a child is diagnosed with Sotos syndrome, it is necessary to conduct an examination of the heart and an ultrasound of the kidneys, and if abnormalities are detected, contact the appropriate specialist. Children with Sotos syndrome should have a thorough check-up every one to two years, which includes back examination for scoliosis, eye examination, blood pressure measurement, and speech and language. If necessary, you should consult with the appropriate specialists.

Clinical assessment should be carried out at an early stage of development and on an ongoing basis to help confirm the presence and extent of developmental delay, psychomotor delay and / or mental retardation backwardness. Such assessment and early intervention can help ensure that appropriate action is taken to help patients reach their highest potential. Special services that may be helpful to affected children include stimulating infants, special education, special social support, physiotherapy, occupational therapy, speech therapy and adaptive physical culture.

A small percentage (2.2 to 3.9%) of people with Sotos syndrome may be more prone to developing certain benign tumors and malignant neoplasms than the general population. Due to the low risk of these problems, the age of onset or detection from infancy to adult age and variable localization (~ 1/3 intra-abdominal, 2/3 extra-abdominal), no recommended routine surveys.

Genetic counseling is recommended for patients and their families.

Forecast

Sotos syndrome is not a life-threatening disease and patients can have a normal life expectancy. The initial abnormalities of Sotos syndrome usually resolve as growth rates return to normal after the first few years of life. Developmental delays may improve during school age, and adults with Sotos syndrome are likely to be within the normal range of intelligence and height. However, coordination problems can persist into adulthood.