- ADNP-related Helsmoortel-Van der Aa syndrome is a single gene autism causing cognitive, behavioural and physical impairments that substantially reduce functioning and quality of life.
- Early diagnosis, comprehensive multidisciplinary evaluations, and individualised treatment planning are essential for assessment, monitoring and caregiver advocacy.
- Systematic review of 209 cases underscores complex symptomatology and evidence limitations due to rarity, small samples and variable symptom reporting.
Am J Med Genet A. 2026 Sep 17. doi: 10.1002/ajmg.a.70288. Online ahead of print.
ABSTRACT
ADNP-related Helsmoortel-Van der Aa syndrome (ADNP-related HVDAS) is a single gene form of autism spectrum disorder (ASD) caused by pathogenic sequence variants in the activity-dependent neuroprotective protein (ADNP) gene. In addition to ASD, ADNP-related HVDAS is associated with a wide range of cognitive, behavioral, and physical health features that may lead to profound impairment in functioning and significantly impact quality of life for affected individuals, their families, and caregivers. However, because it remains rare, most clinicians are not familiar with the syndrome and lack knowledge to guide assessment and monitoring. The goals of this study are to (1) provide an updated systematic review of the clinical manifestations of ADNP-related HVDAS, (2) establish recommendations for assessment and monitoring that can be used by caregivers when advocating for their children, and (3) be applied practically by clinicians caring for affected individuals. A literature review was conducted by searching PubMed, PsycInfo, and Embase databases using “ADNP”, “ADNP Syndrome,” and “Helsmoortel-Van der Aa Syndrome” through July 18, 2026. Articles were included if they reported on clinical manifestations of ADNP-related HVDAS and were excluded if they did not describe at least one individual with the diagnosis. A total of 28 publications met inclusion criteria including case reports, case series, and small cohort studies; data were extracted for 209 cases and organized by clinical domain. A formal risk of bias assessment was not performed, and results were limited by the rarity of ADNP-related HVDAS and thus small sample sizes, as well as variability in symptom reporting. Our updated review highlights the complex symptomatology of ADNP-related HVDAS and the importance of early diagnosis, comprehensive evaluations, and individualized treatment planning.
PMID:42753173 | DOI:10.1002/ajmg.a.70288
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