A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome

Ophthalmic Genet. 2021 Oct;42(5):612-614. doi: 10.1080/13816810.2021.1923040. Epub 2021 May 5.

Abstract

Background: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.Patient and methods: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking.Results: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures.Conclusion: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.

Keywords: Arthrogryposis; Marcus-Gunn; Wieacker-Wolff; duane.

Publication types

  • Case Reports

MeSH terms

  • Apraxias / diagnosis*
  • Apraxias / genetics
  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics*
  • Blepharoptosis / diagnosis
  • Blepharoptosis / genetics*
  • Child
  • Codon, Nonsense
  • Contracture / diagnosis*
  • Contracture / genetics
  • Duane Retraction Syndrome / diagnosis
  • Duane Retraction Syndrome / genetics*
  • Exome Sequencing
  • Female
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Jaw Abnormalities / diagnosis
  • Jaw Abnormalities / genetics*
  • Magnetic Resonance Imaging
  • Muscular Atrophy / diagnosis*
  • Muscular Atrophy / genetics
  • Mutation*
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / genetics*
  • Nuclear Proteins / genetics*
  • Ophthalmoplegia / diagnosis*
  • Ophthalmoplegia / genetics
  • Reflex, Abnormal / genetics*

Substances

  • Codon, Nonsense
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • ZC4H2 protein, human

Supplementary concepts

  • Marcus Gunn phenomenon
  • Wieacker syndrome