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

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.

• Authors: Tímea Margit Szabó, István Balogh, Anikó Ujfalusi, Zsuzsanna Szűcs, László Madar, Katalin Koczok, Beáta Bessenyei, Ildikó Csürke, Katalin Szakszon
• Journal: Genes (Genes (Basel)) Vol. 13 Issue 12 (12 15 2022) ISSN: 2073-4425 [Electronic] Switzerland
• PMID: 36553633 (Publication Type: Case Reports, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• Nerve Tissue Proteins

Topics

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