Helsmoortel-Van der Aa syndrome

The ADNP gene was first identified in murine cells as a vasoactive intestinal peptide (VIP) responsive gene showing increased expression after VIP treatment. VIP is a neuroprotective peptide that is active during embryonic development and protects damaged nerve cells from cell death by inducing survival promoting substances. The ADNP protein contains both DNA and protein binding domains. Interaction partners of the ADNP protein include members of the BAF complex, the functional equivalents of the mating-type switching/sucrose nonfermenting (SWI/SNF) complex in yeast.

The first extensive characterization of ADNP as an autism gene resulted from a ‘genotype-first’ approach in an unbiased genome wide screening of an autism/ID patient cohort for de novo disruptive mutations. In the context of an international collaborative study, we identified a total of 10 patients with mutations in ADNP in our first cohort. All patients suffered from autism, co-morbid with mild to severe intellectual disability. Dysmorphic features included a prominent forehead, high hairline, eversion or notch of the eyelid, broad nasal bridge and thin upper lip. Following our initial report, many additional patients were identified, that share many of the reported characteristics.


Links to additional information and further studies

In order to collect additional clinical information, we set up an ADNP website were clinicians can consult and update the latest information. We keep a listing of all ADNP mutations in the LOVD database. The GenIDA interface is designed for the collection of clinical data from the parents or caretakers directly. In the USA, patients have the opportunity to join the TIGER study for an extensive on site evaluation. The Simons Variation in Individuals Project is also collecting data from patients with an ADNP mutation and run a Simons VIP Connect Community facebook group. A parent support group has constructed a useful website called ADNP kids. The parents also run an active, closed facebook group. Further information is available from Unique at rarechromo.org.

One of our patients