CHD3 syndrome, also known as Snijders Blok-Campeau Syndrome, is a rare neurodevelopmental disorder. It is caused by a genetic change in the CHD3 gene, which severely impacts early brain development. Since its initial identification in 2018, approximately 60 to 150 cases have been described in medical literature. This genetic disorder results in a spectrum of developmental and physical challenges that affect an individual throughout their life.
The CHD3 Gene and Chromatin Remodeling
The cause of CHD3 syndrome lies in the CHD3 gene, which stands for Chromodomain Helicase DNA-binding Protein 3. This gene provides instructions for creating a protein that is a core subunit of the Nucleosome Remodeling and Deacetylase (NuRD) complex. The CHD3 protein regulates gene activity through chromatin remodeling. This process uses energy from ATP to move nucleosomes, which are the structural units that package DNA into chromosomes.
By repositioning these nucleosomes, the CHD3 protein controls how tightly the DNA is packaged, thereby making certain genes more or less accessible for expression. The mutations found in CHD3 syndrome often alter the protein’s ATP-binding domain, which either increases or decreases its chromatin remodeling activity. This disruption during prenatal development leads to the misregulation of numerous other genes that direct the formation of various organs and tissues, particularly affecting the brain.
Key Developmental and Physical Characteristics
The clinical presentation of CHD3 syndrome includes several consistent features. Nearly all affected individuals experience global developmental delay, particularly in speech and language acquisition. Children often speak their first word around two years and ten months of age, and some remain nonverbal. Intellectual disability is also common, with severity ranging widely from borderline to severe impairment.
Motor skills are frequently affected, as most individuals exhibit low muscle tone (hypotonia). This contributes to delays in achieving milestones such as sitting, standing, and walking. Many people with the syndrome also exhibit distinct craniofacial features, including macrocephaly (an unusually large head circumference) in about half of reported cases.
Other common craniofacial traits include:
- Widely-spaced eyes
- A broad forehead
- Sparse eyebrows
- A pointed chin
Ophthalmological problems are frequent, such as farsightedness or strabismus (misalignment of the eyes). Structural abnormalities in the brain, such as enlarged spaces containing cerebrospinal fluid, are seen in about half of the affected population. Behavioral differences are also noted, including traits associated with Autism Spectrum Disorder (ASD) or an unusually friendly demeanor.
Identifying the Syndrome Through Genetic Testing
The identification of CHD3 syndrome begins when a clinician observes severe developmental delay combined with the characteristic physical features. Since symptoms overlap with other neurodevelopmental disorders, a definitive diagnosis requires genetic confirmation. This confirmation is achieved by identifying a pathogenic alteration in the CHD3 gene.
Genetic testing techniques such as whole-exome sequencing (WES) or targeted gene panels are used to analyze the individual’s DNA. These methods specifically look for a heterozygous mutation in the CHD3 gene, which in most cases is a de novo change, meaning it occurs spontaneously and is not inherited from the parents. A confirmed genetic diagnosis provides a clear explanation for the child’s developmental trajectory and is necessary for accessing appropriate support services.
Multidisciplinary Care and Symptomatic Management
Since CHD3 syndrome is a genetic condition, no curative treatment is available. Management focuses on addressing specific symptoms and providing supportive care. This approach necessitates a multidisciplinary team of specialists, including neurologists, developmental pediatricians, genetic counselors, and various therapists. Early and intensive intervention is advised to maximize developmental potential.
Therapeutic interventions are tailored to the individual’s needs:
- Speech and language services are a primary focus due to communication deficits.
- Physical therapy and occupational therapy address low muscle tone and improve motor skills.
- Specialized educational planning, such as Individualized Education Programs (IEPs), ensures academic support for learning challenges.