Helsmoortel-Van der Aa Syndrome as emerging clinical diagnosis in intellectually disabled children with autistic traits and ocular involvement

Giulia Pascolini, Emanuele Agolini, Silvia Majore, Antonio Novelli, Paola Grammatico, Maria Cristina Digilio

Research output: Contribution to journalArticle


A recent syndromic condition with craniofacial dysmorphisms, comprising congenital ocular defect and neurodevelopmental delay named Helsmoortel-Van der Aa Syndrome (HVDAS) (OMIM#615873), has been described and molecularly defined, identifying pathogenic mutations in the ADNP gene (OMIM#611386) as biological cause. We report on two children, displaying intellectual disability (ID) and peculiar congenital eyes anomalies, both carrying a de novo nonsense mutation in the ADNP gene. The review of present and literature reports, suggests that the diagnosis of HVDAS should be suspected in patients with ID accompanied by behavioral features in the Autism Spectrum Disorder and distinctive craniofacial phenotype. Among dysmorphisms due to malformation of the periorbital region, ptosis appears to be particularly recurrent in HVDAS. Furthermore, the present patients could support the inclusion of the HVDAS associated with specific mutations clustering within a small ADNP genomic region among clinical conditions reminiscent of the blepharophimosis/mental retardation syndromes (BMRS).

Original languageEnglish
Pages (from-to)552-557
Number of pages6
JournalEuropean Journal of Paediatric Neurology
Issue number3
Publication statusPublished - May 2018



  • Abnormalities, Multiple/genetics
  • Autistic Disorder/genetics
  • Child, Preschool
  • Craniofacial Abnormalities/genetics
  • Disabled Children
  • Female
  • Homeodomain Proteins/genetics
  • Humans
  • Infant
  • Intellectual Disability/genetics
  • Male
  • Mutation
  • Nerve Tissue Proteins/genetics
  • Phenotype
  • Syndrome

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