Helsmoortel-Van Der Aa syndrome: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: BAGF, age 3, male, born at 37 weeks 3 days of gestational age, vaginal delivery, weighing 2,700 g, 45 cm in length, 35 cm in head circumference, Apgar score of 8/9. At birth, coloboma iris (left), bilateral inguinal hernia and bilateral cryptorchidism were noted. Neural tube defect was suspected; however, magnetic resonance imaging of head and neck and optical nerve were unremarkable, as was his echocardiogram. He initiated follow-up at a tertiary hospital clinic with 10 months of age, presenting with neuropsychomotor developmental delay: responded intermittently to his name, complete cephalic support had just been acquired, did not transfer objects between hands, lallation phase of language. Poor growth and weight gain. Family history was notable for an older brother with delayed language development. On physical examination short halluces, small head, malar flatness, hooded eyelids, broad nasal bridge, round nasal tip, rounded low-set ears were noted, as were bilateral convergent strabismus, truncal ataxia, inability to support oneself while sitting, decreased muscle tone in the axial spine and discrete increase in appendicular muscle tone. Karyotype study revealed 46, XY chromossomes; genetic microarrays were also normal. Ultimately, exoma sequencing revealed a pathogenic in the ADNP gene, allowing for a diagnosis Helsmoortel-Van Der Aa Syndrome or ADNP syndrome.

Discussion: ADNP syndrome is rare, with point prevalence estimated 1-9/100,000 individuals; additionally, it represents an estimated 0.17% of autism spectrum disorder (ASD) cases. The phenotype includes intellectual disability (ID), delays in speech and motor development, as well as behavioral problems. While ADNP patients have higher rates of ID, they present less severe social affect symptoms compared to ASD. Other ADNP symptoms may include seizures, distinct dysmorphic facial features, sensory problems, autistic traits and hypotonia. Congenital heart defects and short stature are also apparent. About 80% of children with ADNP mutations present early deciduous dentation.

Final Comments: Exome sequencing or specific ADNP gene sequencing is required for diagnosis. Some similarities are found with Okihiro, Angelman, Rett and Noonan syndrome, as well as other less common disorders. Supportive care is recommended through speech, occupational, and physical therapy, plus individualized learning programs; support for neuropsychiatric, nutritional/hormonal, cardiac, ophthalmologic and auditory findings are also recommended.

 

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Publication History

Article published online:
12 May 2025