Helsmoortel-Van der Aa Syndrome-Cardiothoracic and Ectodermal Manifestations in Two Patients as Further Support of a Previous Observation on Phenotypic Overlap with RASopathies

Genes (Basel). 2022 Dec 15;13(12):2367. doi: 10.3390/genes13122367.

Abstract

The ADNP-gene-related neurodevelopmental disorder Helsmoortel-Van der Aa syndrome is a rare syndromic-intellectual disability-an autism spectrum disorder first described by Helsmoortel and Van der Aa in 2014. Recently, a large cohort including 78 patients and their detailed phenotypes were presented by Van Dijck et al., 2019, who reported developmental delay, speech delay and autism spectrum disorder as nearly constant findings with or without variable cardiological, gastroenterological, urogenital, endocrine and neurological manifestations. Among cardiac malformations, atrial septal defect, patent ductus arteriosus, patent foramen ovale and mitral valve prolapse were the most common findings, but other unspecified defects, such as mild pulmonary valve stenosis, were also described. We present two patients with pathogenic ADNP variants and unusual cardiothoracic manifestations-Bland-White-Garland syndrome, pectus carinatum superiorly along the costochondral junctions and pectus excavatum inferiorly in one patient, and Kawasaki syndrome with pericardiac effusion, coronary artery dilatation and aneurysm in the other-who were successfully treated with intravenous immunoglobulin, corticosteroid and aspirin. Both patients had ectodermal and/or skeletal features overlapping those seen in RASopathies, supporting the observations of Alkhunaizi et al. 2018. on the clinical overlap between Helsmoortel-Van der Aa syndrome and Noonan syndrome. We observed a morphological overlap with the Noonan-like disorder with anagen hair in our patients.

Keywords: ADNP; Helsmoortel–Van der AA syndrome; Noonan.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple* / genetics
  • Autism Spectrum Disorder* / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Intellectual Disability* / genetics
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Phenotype

Substances

  • Homeodomain Proteins
  • Nerve Tissue Proteins

Grants and funding

Clinical exome sequencing of Patient 1 was supported by the Ministry of National Economy, Hungary (GINOP-2.3.2-15-2016-00039).