What is ADNP?

ADNP syndrome, also known as Helsmoortel-Van der Aa syndrome, is a rare neurodevelopmental disorder caused by mutations in the ADNP gene (Activity-Dependent Neuroprotective Protein). This gene plays a crucial role in brain development, regulation of gene expression, and the formation of synapses, which are essential for communication between nerve cells. When the ADNP gene is altered, it disrupts normal brain function and development, leading to a broad range of clinical features. The condition is considered one of the most common single-gene causes of autism spectrum disorder (ASD), although its presentation extends beyond autism. ​

The syndrome is characterized by global developmental delays, intellectual disability, and speech impairments, often accompanied by autism-like behaviors. Children with ADNP syndrome typically show delayed milestones such as walking and talking, low muscle tone (hypotonia), and challenges with coordination. Distinctive physical features may also be present, including facial differences, feeding difficulties, sleep disturbances, and abnormalities in the gastrointestinal and immune systems. Some individuals may develop seizures, heart defects, or vision and hearing issues, although the severity and combination of symptoms vary widely among patients.

ADNP syndrome is usually diagnosed through genetic testing, often following a clinical evaluation of developmental delays and associated symptoms. ADNP syndrome is caused by just one singular gene, which contains 1102 amino acids. ADNP is part of the SWI/SNF complex and encompasses a number of autistic and intellectual disabilities. ADNP is also the first Mendelian/Monogenic condition with two distinct episignatures caused by mutations in a single gene. These highly sensitive and specific DNA methylation episignatures enable diagnosis, screening, and genetic variant classification in ADNP syndrome.

ADNP has been found to be associated with other major brain disorders and this connection makes ADNP a promising candidate for investment as it may hold the key to unlocking brain disorders that affect millions of people worldwide.

Studies have shown that ADNP dysfunction has been linked to various conditions such as Autism, Alzheimer's, Parkinson's, and Schizophrenia, suggesting that developing therapies for ADNP could also be applicable to more common disorders.

While there is currently no cure, treatment is focused on supportive care such as early intervention therapies (speech, occupational, and physical therapy), behavioral therapies for autism traits, and medical management of associated health problems. Ongoing research is exploring potential targeted treatments, including drug therapies that may help restore some of the disrupted molecular pathways caused by ADNP mutations. With appropriate support, individuals with ADNP syndrome can make progress in their development, though lifelong challenges are common.