SOTOS SYNDROME: SYMPTOMS, CAUSES, TREATMENT - NEUROPSYCHOLOGY - 2025

The Sotos syndrome or "cerebral gigantism" in a genetic disease characterized by excessive physical growth during the early years of life. Specifically, this medical condition is one of the most common overgrowth disorders.

The clinical signs and symptoms of this pathology vary from one individual to another, however, there are several characteristic findings: atypical facial features, exaggerated physical growth during childhood and intellectual disability or cognitive alterations.

In addition, many of the affected individuals also present other series of medical complications such as congenital heart anomalies, seizures, jaundice, kidney anomalies, behavioral problems, among others.

The sotos syndrome has a genetic nature, most of the cases are due to a mutation of the NSD1 gene, located on chromosome 5. The diagnosis of this pathology is established mainly through the combination of clinical findings and studies. genetic

Regarding treatment, there is currently no specific therapeutic intervention for sotos syndrome. Generally, medical care will depend on the clinical characteristics of each individual.

General characteristics of Sotos syndrome

Sotos syndrome, also known as cerebral gigantism, is a syndrome classified within the overgrowth disorders. This pathology was systematically described for the first time by the endocrinologist Juan Sotos, in 1964.

In the first medical reports, the main clinical features of 5 children with overgrowth were described: rapid growth, generalized developmental delay, particular facial features and other neurological disorders.

However, it was not until 1994, when the main diagnostic criteria for Sotos syndrome were established by Cole and Hughes: distinctive facial appearance, excessive growth during childhood, and learning disabilities.

At present, hundreds of cases have been described, in this way we can know that the physical appearance of a child affected by Sotos syndrome is: height higher than expected for their sex and age group, large hands and feet, perimeter cranial with an excessive size, wide forehead and with lateral recesses.

Statistics

Sotos syndrome can occur in 1 in 10,000-14,000 newborn infants.

However, the true prevalence of this pathology is not exactly known, since the variabilities of its clinical characteristics tend to be confused with other medical conditions, so it is likely that it is not diagnosed correctly.

Different statistical studies indicate that the real incidence of Sotos syndrome can reach a figure of 1 in every 5,000 individuals.

Although Sotos syndrome is often considered a rare or rare disease, it is one of the most common overgrowth disorders.

Regarding the particular characteristics, Sotos syndrome can affect men and women in the same proportion. In addition, it is a medical condition that can occur in any geographic area and ethnic group.

Signs and symptoms

Various investigations, through the analysis of hundreds of affected patients, have described and systematized the most frequent signs and symptoms of Sotos syndrome:

Clinical findings present in 80% -100% of cases

Above average head circumference (macrocephaly); elongated skull (dolichocephaly); structural alterations and malformations in the central nervous system; bulging or prominent forehead; high hairline; rosy appearance on cheeks and nose; elevated palate; increased height and weight; accelerated and / or exaggerated growth during childhood; large hands and feet; abnormally reduced muscle tone (hypotonia); generalized developmental delay; linguistic disturbances.

Clinical findings present in 60-80% of cases

Bone age higher than the biological or natural age; early eruption of teeth; delayed acquisition of fine motor skills, torsion of palpebral fissures; chin pointed and prominent; IQ below normal range; learning difficulties, scoliosis; recurrent respiratory tract infections; behavioral disturbances and disorders (hyperactivity, language disorders, depression, anxiety, phobias, alteration of sleep-wake cycles, irritability, stereotyped behaviors, etc.).

Clinical findings present in less than 50% of cases

Abnormal feeding and reflux processes; hip dislocation; strabismus and nystagmus; convulsive episodes; congenital heart disease; jaundice, etc.

More specifically, below, we will describe the most common symptoms based on the affected areas.

Physical characteristics

Among the physical alterations, the most relevant clinical findings refer to growth and development, skeletal maturation, facial alterations, cardiac anomalies, neurological alterations and neoplastic processes.

Overgrowth

In most cases of thicket syndrome, approximately 90% of individuals have a height and head circumference above the average, that is, above the expected values ​​for their sex and age group.

From the moment of birth, these developmental characteristics are already present and, in addition, the growth rate is abnormally accelerated, especially during the first years of life.

Despite the fact that the height is higher than expected, the growth standards tend to stabilize in the adult stage.

On the other hand, skeletal maturation and bone age tend to be ahead of biological age, so they tend to adjust to stature age. Also, in children with scrub syndrome, it is not unusual to see an early tooth eruption.

Craniofacial alteration

Facial characteristics are one of the central findings in sotos syndrome, especially in young children. The most common facial features usually include:

- Redness.

- Scarcity of hair in fronto-temporal areas.

- Low hairline.

- Raised forehead.

- Inclination of the palpebral fissures.

- Long and narrow facial configuration.

- chin pointed and bulging or prominent.

Although these facial characteristics are still present in adulthood, with the passage of time they tend to be more subtle.

Heart abnormalities

The probability of the presence and development of cardiac abnormalities is significantly increased compared to the general population.

It has been observed that approximately 20% of people with sotos syndrome have some type of associated cardiac abnormality.

Some of the most common cardiac alterations are: atrial or interventricular communication, persistence of ductus arteriosus, tachycardia, etc.

Neurological disorders

At a structural and functional level, various anomalies have been detected in the central nervous system: ventricular dilation, hypoplasia of the corpus callosum, brain atrophy, cerebolic atrophy, intracranial hypertension, among others.

Due to these, it is common for individuals with sotos syndrome to present significant hypotonia, impaired development and coordination of movements, hyperrleflexia, or seizures.

Neoplastic processes

Neoplastic processes or the presence of tumors are present in about 3% of individuals suffering from sotos syndrome.

In this way, various benign and malignant tumors related to this pathology have been described: neuroblastomas, carcinomas, cavernous hemangioma, Wilms tumor, among others.

In addition to all these characteristics, we can also find other types of physical alterations such as scoliosis, kidney abnormalities or feeding difficulties.

Psychological and cognitive characteristics

Generalized developmental delay and especially motor skills are one of the most common findings in Sotos syndrome.

In the case of psychomotor development, it is common to observe poor coordination and difficulty in the acquisition of motor and fine skills. Thus, one of the most significant repercussions of poor motor development is the dependency and limitation of autonomous development.

We can also observe an evident delay in expressive language. Although they tend to understand expressions, linguistic formulations or communicative intention normally, they have difficulties expressing their wishes, intentions or thoughts.

On the other hand, at a cognitive level it has been detected that between 60 and 80% of individuals suffering from Sotas syndrome have learning difficulties or a variable mental disability from mild to slight.

Causes

Sotos syndrome is a disease of genetic origin, due to an abnormality or mutation of the NSD1 gene located on chromosome 5.

This type of genetic alteration has been identified in approximately 80-90% of the cases of Sotos syndrome. In these cases, the term Sotos syndrome 1 is often used.

The essential function of the NSD1 gene is to produce various proteins that control the activity of genes that are involved in normal growth, development, and maturation.

In addition, recently other types of alterations related to Sotos syndrome have also been identified, specifically mutations in the NFX gene, located on chromosome 19. In these cases, the term Sotos syndrome 2 is often used.

The Sotos syndrome presents a sporadic occurrence, mainly due to Novo genetic mutations; however, cases have been detected in which there is an autosomal dominant form of inheritance.

Diagnosis

Currently, no specific biological markers have been identified that confirm the unequivocal presence of this pathology. The diagnosis of Sotos syndrome is made on the basis of physical findings observed in clinical examinations.

In addition, when there is clinical suspicion, other complementary tests are usually requested, such as genetic studies, bone age X-rays or magnetic resonance imaging.

As for the usual age of diagnosis, these tend to vary depending on the cases. In some individuals, Sotas syndrome is detected after birth, due to the recognition of facial features and other clinical characteristics.

However, the most common is that the establishment of the diagnosis of Sotas syndrome is delayed until the moment in which the usual developmental milestones begin to be delayed or present in an abnormal and altered way.

Treatments

Currently there is no specific therapeutic intervention for Sotos syndrome, these should be oriented towards the treatment of medical complications derived from the clinical entity.

In addition to medical monitoring, people with Sotos syndrome will require a specific psychoeducational intervention, due to the generalized delay in development.

In the first years of life and throughout the childhood stage, early stimulation programs, occupational therapy, speech therapy, cognitive rehabilitation, among others, will be beneficial for the readjustment of maturation processes.

In addition, in some cases, individuals with Sotos syndrome may develop various behavioral alterations that can result in a failure in school and family interaction, in addition to interfering with the learning processes. Because of this, psychological intervention is required to develop the most appropriate and effective methods of solution.

Sotos syndrome is not a pathology that puts the survival of the affected person at serious risk, generally the life expectancy is not reduced compared to the general population.

The characteristic features of Sotos syndrome usually resolve after the early stages of childhood. For example, growth speed tends to slow down and delays in cognitive and psychological development often reach a normal range.

References

1. Spanish Association Sotos Syndrome. (2016). WHAT IS SOTOS SYNDROME? Obtained from the Spanish Association Sotos Syndrome.
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4. Lapunzina, P. (2010). SOTOS SYNDROME. Protocol diagnost ter pediatr., 71-79.
5. NIH. (2015). What is Sotos Syndrome? Obtained from National Institute of Neurological Disorders and Stroke.
6. NIH. (2016). Sotos syndrome. Obtained from Genetics Home Reference.
7. NORD. (2015). Sotos Syndrome. Obtained from National Organization for Rare Disorders.
8. Pardo de Santillana, R., & Mora González, E. (2010). Chapter IX. Sotos syndrome.
9. Tatton-Brown, K., & Rahman, N. (2007). Sotos syndrome. European Journal of Human Genetics, 264-271.