He Sotos syndrome or "Cerebral gigantism" In a genetic pathology characterized by exaggerated physical growth during the first years of life (National Institute of Neurological Disorders and Stroke, 2015).
Specifically, this medical condition is one of the most common disorders of overgrowth (Baujat & Cromier-Daire, 2007).
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 (overgrowth) during childhood and Intellectual disability or Cognitive impairment (Genetics Home Reference, 2016).
In addition, much of the affected individuals also present another series of medical complications such as congenital cardiac anomalies, Convulsive, jaundice , Renal anomalies, behavioral problems, among others (Lapuzina, 2010).
Sotos syndrome has a genetic nature, most of which are due to a mutation of the NSD1 gene, located on chromosome 5 (National Institute of Neurological Disorders and Stroke, 2015).
The diagnosis of this pathology is established mainly through the combination of clinical findings and genetic studies (Lapuzina, 2010).
Regarding treatment, there is currently no specific therapeutic intervention for the syndrome of stumps. Generally, medical care is Depending on the clinical characteristics of each individual (Spanish Association Sotos Syndrome, 2016).
General Characteristics of Sotos Syndrome
Sotos syndrome, also known as cerebral gigantism, is a syndrome classified as an overgrowth disorder (Cortés-Saladelafont et al., 2011).
This pathology was first described systematically by the endocrinologist Juan Sotos, in 1964 (Tatton-Brown & Rahman, 2007).
In the first medical reports, the main clinical features of 5 children with overgrowth (Lapuzina, 2010) were described: fast growth, Generalized developmental delay, particular facial features, and other neurological disorders (Sotos et al., 1964; Pardo de Santillana y Mora Page 2
However, it was not until 1994, when the main diagnostic criteria for Sotos syndrome were established by Cole and Hughes: facial appearance Differentiation, excessive growth during childhood, and learning problems (Tatton-Brown & Rahman, 2007).
At present, hundreds of cases have been described, so we can know that the physical appearance of a child affected by Sotos syndrome is: Higher height than expected for their sex and age group, large hands and feet, cranial perimeter with oversized size, wide forehead and sagging Lateral (Pardo de Santillana and Mora González, 2010).
About us
Sotos syndrome can occur in 1 in 10,000-14,000 newborns (Genetics Home Reference, 2016).
However, the actual prevalence of this pathology is not known with accuracy, since the variabilities of its clinical characteristics tend to Be confused with other medical conditions, so it is probably not correctly diagnosed (Genetics Home Reference, 2016).
Different statistical studies indicate that the actual incidence of Sotos syndrome can reach a figure of 1 per 5,000 individuals (Genetics Home Reference, 2016).
Although Sotos syndrome is often considered a rare or rare disease, it is one of the most frequent disorders of overgrowth (Spanish Association of Sotos Syndrome, 2016).
As for the particular characteristics, Sotos syndrome can affect men and women in the same proportion. In addition, it is a condition Which can occur in any geographical area and ethnic group (National Organization for Rare Disorders, 2015).
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 (Lapuzina, 2010):
- Clinical findings present in 80% -100% of cases: cranial perimeter above the mean ( Macrocephaly ); Elongated skull (Dolicocephaly); Alterations and structural malformations in the central nervous system; Brow bulging or prominent; Capillary birth line high; Pinkish appearance on cheeks and nose; High palate; Increased height and weight; Accelerated and / or exaggerated growth during the infantile stage; hands And large feet; Abnormally reduced muscle tone (hypotonia); Generalized developmental delay; Linguistic alterations.
- Clinical findings present in 60-80% of the cases: bone age superior to the biological or biological; Early eruption of the pieces Dental; Delayed acquisition of fine motor skills, torsion of palpebral fissures; Chin pointed and prominent; CI Below range normal; learning difficulties, scoliosis ; Recurrent infections of the respiratory tract; Disorders and behavioral disorders ( Hyperactivity , Language disorders , depression , anxiety , Phobias, Alteration of sleep-wake cycles , Irritability, stereotyped behaviors, etc.).
- Clinical findings present in less than 50% of the cases: abnormal feeding and reflux processes; Dislocation of hips; Strabismus and nystagmus; Convulsive episodes; Congenital heart defects; Jaundice, etc.
More specifically, we will then describe the most common symptoms depending on the affected areas (Pardo de Santillana and Mora González, 2010; Lapuzina, 2010):
Physical characteristics
Within the physical alterations, the most relevant clinical findings refer to growth and development, skeletal maturation, alterations Facials, cardiac anomalies, neurological alterations and neoplastic processes.
Overgrowth
In most cases of Sotos syndrome, approximately 90% of the individuals present a size and cranial perimeter above the Mean, 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 speed of growth is abnormally accelerated, Especially during the first years of life.
Although higher than expected height, growth standards have to stabilize in the adult stage.
On the other hand, the skeletal maturation and the bone age have to be advanced to the biological age, reason why they have to adjust to the statural age.
In addition, in children with Sotos syndrome, it is not uncommon to see an early dental eruption.
Craniofacial alteration
Facial specificities are one of the central findings in Sotos syndrome, especially in young children.
The most common facial features usually include:
- Redness.
- Shortage of hair in fronto-temporal areas.
- Low capillary birth line.
- High front.
- Inclination of palpebral fissures.
- Long and narrow facial configuration.
- Pointy and bulging or prominent chin.
Although these facial features are still present in adulthood, over time they have to be more subtle.
Cardiac abnormalities
The probability of presence and development of cardiac anomalies increases significantly 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: interatrial or interventricular communication, persistent ductus arteriosus, tachycardia, etc.
Neurological disorders
At the structural and functional level, various abnormalities have been detected in the central nervous system: ventricular dilatation, hypoplasia of the hard body , Cerebral atrophy , Cerebellar atrophy, intracranial hypertension, among others.
Because of these, it is common for individuals with sotos syndrome to present significant hypotonia, developmental dysfunction and Movements, hyperrleflexia or convulsive processes.
Neoplastic Processes
Neoplastic processes or the presence of tumors are present in about 3% of individuals with Sotos syndrome.
In this way, several benign and malignant tumors related to this pathology have been described: Neuroblastomas , Carcinomas, hemangioma Cavernous, Wilms tumor, among others.
In addition to all these characteristics, we can also find other physical alterations such as scoliosis, renal anomalies or difficulties for feeding.
Psychological and cognitive characteristics
Generalized developmental delays and especially motor skills are one of the most common findings in Sotos syndrome.
In the case of psychomotor development, it is frequent to observe poor coordination and difficulty in acquiring motor and fine skills.
Thus, one of the most significant repercussions of poor motor development is the dependence and limitation of autonomous development.
On the other hand, we can also observe an evident delay of expressive language. Although they usually understand expressions normally, Linguistic formulations or communicative intention, present difficulties in expressing their desires, intentions or thoughts.
On the other hand, it has been detected at the cognitive level that between 60 and 80% of the individuals with Sotas syndrome present Learning or a mild to moderate variable mental disability.
Causes
Sotos syndrome is a disease of genetic origin, due to an abnormality or mutation of the NSD1 gene located on chromosome 5 (National Organizatio for Rare Disorders, 2015).
This type of genetic alteration has been identified in approximately 80-90% of cases of Sotas syndrome. In these cases, the Term of Sotos Syndrome 1 (National Organization for Rare Disorders, 2015).
The essential function of the NSD1 gene is to produce various proteins that control the activity of genes that are involved in growth, development And normal maturation (Genetics Home Reference, 2016).
In addition, other types of alterations related to the Sotos syndrome have also recently been identified, Mutations of the NFX gene, located in the Chromosome 19 . In these cases, the term Sotos Syndrome 2 (National Organization for Rare Disorders, 2015).
Sotos syndrome presents a sporadic occurrence, due mainly to genetic mutations of Novo, however, cases have been detected in the That there is a form of autosomal dominant inheritance (Lapuzina, 2010).
Diagnosis
Currently, no specific biological markers have been identified to confirm the unequivocal presence of this pathology (National Organization for Rare Disorders, 2015).
The diagnosis of Sotos syndrome is based on the physical findings observed in clinical examinations (Baujat & Cromier-Daire, 2007).
In addition, other complementary tests, such as genetic studies, bone-age radiographs or Magnetic resonance imaging (Lapuzina, 2010).
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 recognition of facial features and other clinical features (Child Growth Foundation, 2016).
However, the most common is that the establishment of the diagnosis of Sotas syndrome is delayed until such time as the usual Develop or be abnormal or altered (Child Growth Foundation, 2016).
Treatments
There is currently no specific therapeutic intervention for Sotos syndrome, these should be oriented towards the treatment of complications Of the clinical entity (Pardo de Santillana and Mora González, 2010).
In addition to medical follow-up, people with Sotos syndrome will require specific psychoeducational intervention due to delay Development (Pardo de Santillana and Mora González, 2010).
In the early years of life and throughout the infantile stage, the programs of early stimulation, Occupational therapy , Speech therapy, rehabilitation Cognitive, among others, will be beneficial for the readjustment of maturation processes (Baujat & Cromier-Daire, 2007).
In addition, in some cases, individuals with Sotos syndrome may develop various behavioral changes that may result A failure in school and family interaction, as well as interfere with learning processes. Because of this, intervention is required. To develop the most appropriate and effective methods of solution (Baujat & Cromier-Daire, 2007).
The syndrome of Sotos is not a pathology that puts in serious risk the survival of the person affected, generally the life expectancy is not seen Reduced compared to the general population (National Institute of Neurological Disorders and Stroke, 2015).
The characteristic features of Sotos syndrome usually resolve after the early stages of childhood. For example, the rate of growth tends To slow down and delays in cognitive and psychological development usually reach a normal range (National Institute of Neurological Disorders and Stroke, 2015).
References
- Spanish Association Sotos Syndrome. (2016). WHAT IS SOTOS SYNDROME? Obtained from Spanish Association Sotos Syndrome.
- Baujat, G., & Cormier-Daire, V. (2007). Sotos syndrome. Orphanet Journal of Rare Diseases.
- Bravo, M., Chacón, J., Bautista, E., Pérez-Camacho, I., Trujillo, A., & Grande, M. (1999). Sotos syndrome associated with focal dystonia. Rev Neurol, 971-972.
- Lapunzina, P. (2010). SOTH SYNDROME. Protoc diagn. Pediatr., 71-79.
- NIH. (2015). What is Sotos Syndrome? Retrieved from the National Institute of Neurological Disorders and Stroke.
- NIH. (2016). Sotos syndrome. Retrieved from the Genetics Home Reference.
- NORD. (2015). Sotos Syndrome. Retrieved from the National Organization for Rare Disorders.
- Pardo de Santillana, R., & Mora González, E. (2010). Chapter IX. Sotos Syndrome.
- Tatton-Brown, K., & Rahman, N. (2007). Sotos syndrome. European Journal of Human Genetics, 264-271.