A novel variant in DOCK6 gene associated with Adams-Oliver syndrome type 2

Ophthalmic Genet. 2020 Aug;41(4):377-380. doi: 10.1080/13816810.2020.1776339. Epub 2020 Jun 5.

Abstract

Background: Adams-Oliver syndrome (AOS) is a rare, inherited multi-systemic malformation syndrome characterized by a combination of aplasia cutis congenita and transverse terminal limb defects along with variable involvement of the central nervous system, eyes, and cardiovascular system. AOS can be inherited as both autosomal-dominant and recessive traits. Pathogenic variants in the DOCK6, ARHGAP31, EOGT, RBPJ, DLL4, and NOTCH1 genes have been associated with AOS.

Purpose: To report a novel homozygous variant in the DOCK6 gene associated with Adams-Oliver syndrome type 2.

Materials and methods: Case report.

Results: We report a case of a 4-month-old male who presented with microcephaly, global developmental delay, truncal hypotonia, and limb reduction defects. Ophthalmic examination revealed bilateral nystagmus and retinal detachment with mild cataractous changes in addition to retrolental plaque in the left eye. Next generation sequencing analysis identified a novel homozygous frameshift likely pathogenic variant (c.1269_1285dup (p.Arg429Glnfs*32)) in the DOCK6 gene. The constellation of the clinical findings and the genetic mutation were consistent with a diagnosis of AOS type 2.

Conclusion: The discovery of this new likely pathogenic variant enriches the genotypic spectrum of DOCK6 gene and contributes to genetic diagnosis and counseling of families with AOS. Neurologic and ocular findings appear to be consistent with AOS type 2 for which multidisciplinary clinical evaluation is crucial.

Keywords: DOCK6 gene; Adams-Oliver syndrome; aplasia cutis congenita; pediatric retinal detachment; transverse terminal limb defects.

Publication types

  • Case Reports

MeSH terms

  • Ectodermal Dysplasia / genetics
  • Ectodermal Dysplasia / pathology*
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Infant
  • Limb Deformities, Congenital / genetics
  • Limb Deformities, Congenital / pathology*
  • Male
  • Mutation*
  • Phenotype
  • Prognosis
  • Scalp Dermatoses / congenital*
  • Scalp Dermatoses / genetics
  • Scalp Dermatoses / pathology

Substances

  • DOCK6 protein, human
  • Guanine Nucleotide Exchange Factors

Supplementary concepts

  • Adams Oliver syndrome