Van der Woude syndrome and amniotic band sequence: A clue to a common genetic etiology? A case report.

Abstract

Rare heterozygous variants in IRF6 (interferon regulatory factor-6) gene cause van der Woude syndrome 1 (VWS1) or Popliteal Pterygium syndrome, two forms of syndromic cleft lip/palate (CLP) that present with a variety of congenital malformations due to impairment ectodermal homeostasis. These malformations include, in addition to CLP, lip pits, pterygia, and intraoral and eyelid fibrous bands. Amniotic band sequence (ABS) is a rare condition of unknown genetic etiology that involves a range of congenital anomalies caused by the entanglement of fibrous bands, which disrupt fetal body parts. However, ABS co-occurs with CLP and other malformations that cannot be explained by this mechanism. Therefore, investigating the genetic relationship between ABS and CLP may provide clues regardind the genes involved in these conditions. Here, we report a case of a girl diagnosed with VWS1, autism, intellectual disability, and congenital right limb anomalies compatible with ABS. Molecular analysis revealed a novel, rare heterozygous missense variant in IRF6 (NM_006147.3:c.970T>C) located in exon 7, inherited from her father. This variant results in the replacement of serine by proline at position 324 of the IRF6 protein with potentially deleterious effects. This report expands the mutational landscape of IRF6 and provides further support for a possible link between the genetics of CLP and ABS.