Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP
ADNP Consortium
Background In genome-wide screening studies for de novo mutations underlying autism and intellectual disability, mutations in the ADNP gene are consistently reported among the most frequent. ADNP mutations have been identified in children with autism spectrum disorder comorbid with intellectual disability, distinctive facial features, and deficits in multiple organ systems. However, a comprehensive clinical description of the Helsmoortel-Van der Aa syndrome is lacking. Methods We identified a worldwide cohort of 78 individuals with likely disruptive mutations in ADNP from January 2014 to October 2016 through systematic literature search, by contacting collaborators, and through direct interaction with parents. Clinicians filled in a structured questionnaire on genetic and clinical findings to enable correlations between genotype and phenotype. Clinical photographs and specialist reports were gathered. Parents were interviewed to complement the written questionnaires. Results We report on the detailed clinical characterization of a large cohort of individuals with an ADNP mutation and demonstrate a distinctive combination of clinical features, including mild to severe intellectual disability, autism, severe speech and motor delay, and common facial characteristics. Brain abnormalities, behavioral problems, sleep disturbance, epilepsy, hypotonia, visual problems, congenital heart defects, gastrointestinal problems, short stature, and hormonal deficiencies are common comorbidities. Strikingly, individuals with the recurrent p.Tyr719* mutation were more severely affected. Conclusions This overview defines the full clinical spectrum of individuals with ADNP mutations, a specific autism subtype. We show that individuals with mutations in ADNP have many overlapping clinical features that are distinctive from those of other autism and/or intellectual disability syndromes. In addition, our data show preliminary evidence of a correlation between genotype and phenotype.
Source (journal)
Biological psychiatry / Society of Biological Psychiatry [Jacksonville, Fla] - New York, N.Y., 1969, currens
New York, N.Y. : Elsevier , 2019
0006-3223 [print]
1873-2402 [online]
85 :4 (2019) , p. 287-297
Pubmed ID
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
Research group
Project info
Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy ua_40401
The pleiotropic effects of ADNP in Mental Disorders (ADNPinMED). ua_41837
GENOMED - Genomics in Medicine. ua_31389
The role of the AnkyrinG interactome in neurodevelopmental disorders. ua_31408
Publication type
Publications with a UAntwerp address
External links
Web of Science
Creation 05.11.2018
Last edited 01.06.2023
To cite this reference