Sotos Syndrome

What Causes Sotos Syndrome?

Most cases of Sotos syndrome are caused by abnormal changes (mutations) in a gene called the NSD1 gene. This gene carries instructions for making a protein called nuclear receptor-binding SET domain protein 1. NSD1 plays a role in a process in which other genes are turned on and off. NSD1 controls genes that regulate growth and development, and the Sotos syndrome mutations interfere with the normal gene-regulation process. However, scientists have not yet identified all the genes controlled by NSD1, and it’s not clear how the mutations cause the symptoms of Sotos syndrome.

Is Sotos Syndrome Hereditary?

In almost all cases, the genetic mutations that cause Sotos syndrome occur spontaneously during the development of sperm or egg cells and are not present in the parents’ genes. In these cases, the syndrome is not inherited, and the child has no family history of the disorder.

In a small number of cases, Sotos syndrome does run in families, and the gene mutations may be inherited. In these cases, the disorder is inherited in an autosomal dominant pattern, meaning that children may develop the condition if they inherit even one copy of the mutated gene from either of their parents. If a parent carries the disorder-causing mutation, they will have a 50 percent chance of having an affected child with each pregnancy.

How Is Sotos Syndrome Detected?

Sotos syndrome is usually diagnosed by the appearance of its distinctive head and facial features. Doctors will likely suspect the condition when a baby has these features, combined with excessive growth and developmental delays.

How Is Sotos Syndrome Diagnosed?

Sotos syndrome may be diagnosed when a physical exam shows the distinctive physical features of the disorder, including a larger than normal head and characteristic facial features, along with a faster than normal growth rate and developmental symptoms.

Doctors will likely take further diagnostic steps to rule out other possible causes for the symptoms and confirm a diagnosis of Sotos syndrome.  The diagnostic process may include:

• Assessment of the child’s medical and family history
• Physical and neurological exams
• Genetic testing to look for gene mutations associated with Sotos syndrome

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Sotos Syndrome Treated?

Sotos syndrome has no cure, and no treatment will reverse its effects. Treatment approaches after diagnosis will depend on the individual child’s symptoms. Treatment will focus on managing those symptoms and preventing complications. Common treatments and therapies include:

• Monitoring of developmental delays and impairments
• Monitoring of heart and kidney health
• Monitoring of spine development
• Physical therapy
• Occupational therapy
• Speech therapy
• Special education

How Does Sotos Syndrome Progress?

Sotos syndrome is not progressive, and a child’s growth rate will usually slow into the normal range after early childhood. Adults with the disorder typically achieve average height. Developmental delays also tend to improve later in childhood, and average intelligence in adulthood is common.

In some cases, some symptoms persist, and some complications may be long-term, including:

• Intellectual disability
• Problems with coordination and balance
• Social and behavioral problems

How Is Sotos Syndrome Prevented?

There is no known way to prevent Sotos syndrome. Parents with a family history of the disorder are advised to consult a genetic counselor to assess their risk if they plan to have a child.

Sotos Syndrome Caregiver Tips

• Be an advocate for your child. Learn all you can about Sotos syndrome so you can understand the challenges your child faces, and be better prepared to educate others about what they can do to help and support you and your child.
• Remember that you’re not alone. The Sotos Syndrome Support Association offers resources and connections to other families living with the disorder.

Some people with Sotos syndrome also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with Sotos syndrome:

• Many children with Sotos syndrome show signs of autism, and the two disorders may be co-morbid.
• Some children with Sotos syndrome exhibit symptoms of attention-deficit/hyperactivity disorder (ADHD).
• Anxiety is common in children with Sotos syndrome.

Sotos Syndrome Brain Science

Scientists don’t yet understand how and why Sotos syndrome affects the brain. Mutations in the NSD1 gene likely cause disruptions in a child’s normal growth process, resulting in the distinctive physical features of the disorder. It is unclear how these mutations affect brain function and produce the cognitive, behavioral, and social symptoms common in Sotos syndrome.

One study has examined the overlap in symptoms between Sotos syndrome and autism spectrum disorder (ASD). The study found several behavioral symptoms to be shared in people with both disorders, including:

• Social anxiety
• Compulsive behaviors
• Limited interests
• Repetitive speech patterns
• Preference for routines

Although the study results don’t necessarily help explain why NSD1 mutations cause behavioral symptoms, they suggest a potentially enlightening connection between Sotos syndrome and autism. The implication that people with Sotos syndrome may have behavioral traits in common with people on the autism spectrum and that NSD1 mutations may play a role in ASD could provide direction for future research.

Sotos Syndrome Research

Title: Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

Stage: Recruiting

Principal investigator: Cora Taylor, PhD

Geisinger Health System

Lewisburg, PA

Simons Searchlight collects medical, behavioral, learning, and developmental information from people with gene changes linked to autism and other neurodevelopmental disorders. The goal of this study is to improve the clinical care and treatment for these people. Simons Searchlight partners with families to collect data and distribute it to qualified researchers.

Simons Searchlight has expanded over the last several years to include additional gene changes and participation through remote formats, either online or by phone. This allows English and Spanish-speaking families from across the world to participate at times that are convenient to their schedule. Participants can donate blood, saliva, or both. These samples are then linked to medical, behavioral, learning, and developmental data to understand the effects of specific gene changes.

Information provided by participants will be stripped of any personally identifying information and made available to qualified scientists around the world.

The Simons Foundation, a New York-based private foundation, is committed to finding science-based solutions and developing targeted treatments to improve the lives of people who have genetic and developmental differences.

Title: Genetics, Brain Structure and Thinking Skills in Autism

Stage: Completed

Principal investigator: Thomas W Frazier, PhD

The Cleveland Clinic

Cleveland, OH 

This research aims to understand better the genetic, biochemical, cognitive, and behavioral symptom abnormalities that contribute to autism spectrum disorders. The investigators anticipate recruiting at least 100 participants with autism spectrum disorder and large head size, at least 100 participants with autism spectrum disorder without large head size, and at least 40 healthy siblings. Biological parents are expected to be recruited only as genetic changes are identified in individuals with autism spectrum disorders to better understand the nature of these genetic changes. Participants are asked to complete cognitive testing, a blood draw, urine collection, and measurement of their height, weight, and head circumference. Parents or caregivers may be asked to complete a diagnostic evaluation and will complete questionnaires that examine the participant’s medical and family history as well as their current symptoms, functioning, and quality of life. A brief report simply listing and giving a basic description of any behavioral diagnostic information, autism symptoms, adaptive functioning, and a listing of results from cognitive testing will be provided as part of this study.

Title: Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations

Stage: Recruiting

Principal investigator: Julian Martinez, MD, PhD

University of California at Los Angeles

Los Angeles, CA

Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterized by social communication/interaction impairments and restricted/repetitive behaviors. ASD associated with germline heterozygous PTEN mutations (PTEN ASD) is a genetically defined sub-group that may be one of the more prevalent genetic disorders contributing to ASD (0.5-2%). The purpose of this research study is to carefully track the phenotypic and molecular characteristics of PTEN ASD and identify biomarkers for intervention studies.

Individuals with PTEN ASD, with macrocephalic ASD without a PTEN mutation (macro-ASD), healthy controls, and individuals with PTEN mutations without ASD (PTEN no-ASD) will be asked to participate in this study if they are 18 months and older. Both males and females will be invited to participate. Additionally, to be eligible for study participation, individuals’ primary communicative language must be English.

The study involves three on-site visits over two years. Study visits will vary in length from about 4 hours to 6 hours. Study visits involve a physical exam, medical history questions, neuropsychological assessments, and a blood draw done for laboratory studies. A subset of participants between the ages of 2 and 11 will participate in the study’s EEG portion. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.