ATP7A mutation with occipital horns and distal motor neuropathy: A continuum

Eur J Med Genet. 2020 Dec;63(12):104087. doi: 10.1016/j.ejmg.2020.104087. Epub 2020 Oct 31.

Abstract

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489) (Kennerson et al., 2010). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein (Møller, 2015). Thus far OHS and SMAX3 only partially overlap. In fact patients with OHS usually have no distal motor neuropathy signs but, on the other hand, occipital horns, which are the main sign of OHS, have not been described in SMAX3 patient. We describe here a patient bearing a missense ATP7A mutation with associated signs of distal motor neuropathy as well as occipital horns, confirming that OHS and SMAX3 are a continuum.

Keywords: ATP7A; Dysautonomia; Menkes disease; Occipital horn syndrome; X-linked distal spinal muscular atrophy-3.

Publication types

  • Case Reports

MeSH terms

  • Copper-Transporting ATPases / genetics*
  • Cutis Laxa / genetics*
  • Cutis Laxa / pathology
  • Ehlers-Danlos Syndrome / genetics*
  • Ehlers-Danlos Syndrome / pathology
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Male
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / pathology
  • Mutation, Missense
  • Phenotype

Substances

  • ATP7A protein, human
  • Copper-Transporting ATPases

Supplementary concepts

  • Occipital horn syndrome
  • Spinal Muscular Atrophy, Distal, X-Linked 3