Clinical characteristics: ADNP-related intellectual disability and autism spectrum disorders (ADNP-related ID/ASD) are characterized by mild to severe intellectual disability and autism spectrum disorder (ASD). Of the 24 individuals reported to date, 23 were ascertained in cohorts with autism spectrum disorder (ASD) / intellectual disability (ID); one was identified in a clinical setting. The clinical information available on 12 of the 24 revealed: delayed developmental milestones (walking independently between 19 months and 4.5 years) and speech ranging from no words to sentences. ASD was characterized by stereotypic behavior and impaired social interaction. Other common findings include behavioral problems, sleep disturbance, hypotonia, seizures, feeding difficulties, visual problems (hypermetropia, strabismus, cortical visual impairment), and cardiac defects.
Diagnosis/testing: The diagnosis of ADNP-related ID/ASD is established by identification of a heterozygous ADNP pathogenic variant on molecular genetic testing.
Management: Treatment of manifestations: Treatment is symptomatic and can include: speech, occupational, and physical therapy; specialized learning programs depending on individual needs; treatment of neuropsychiatric features (e.g., sleep disorders, behavioral problems, and/or seizures); nutritional support as needed; routine treatment of ophthalmologic and cardiac findings.
Genetic counseling: ADNP-related ID/ASD is expressed in an autosomal dominant manner. Given that all affected individuals with ADNP-related syndromic autism reported to date have the disorder as a result of a de novo ADNP pathogenic variant, the risk to other family members is presumed to be low. Prenatal testing and preimplantation genetic diagnosis are possible options.
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