Peripheral neuropathy and 46XY gonadal dysgenesis: a heterogeneous entity

Neuromuscul Disord. 2009 Feb;19(2):172-5. doi: 10.1016/j.nmd.2008.11.006. Epub 2009 Jan 22.

Abstract

Gonadal dysgenesis with normal male karyotype (46XY) is a sexual differentiation disorder. So far three patients have been reported presenting the association of 46XY gonadal dysgenesis with peripheral neuropathy. Examination of sural nerves revealed minifascicle formation in two of them. In one patient, a mutation was found in desert hedgehog homolog (Drosophila), a gene important in gonadal differentiation and peripheral nerve development. We studied neuropathological and molecular genetic aspects of a patient with 46XY gonadal dysgenesis and peripheral neuropathy. Examination of a sural nerve biopsy specimen revealed an axonal neuropathy with pronounced axonal loss, limited signs of axonal regeneration and no minifascicle formation. A normal male karyotype was found (46XY) without micro-deletions in the Y chromosome. No mutations were found in the sex determining region Y gene, peripheral myelin protein 22, Myelin Protein Zero, Gap-Junction protein Beta 1, Mitofusin 2 or desert hedgehog homolog. The absence of minifascicle formation and the absence of a mutation in desert hedgehog homolog in this patient with gonadal dysgenesis and peripheral neuropathy expand the clinical and genetic heterogeneity of this rare entity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axons / metabolism
  • Axons / pathology
  • Biopsy
  • Comorbidity
  • DNA Mutational Analysis
  • Female
  • Gene Dosage / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genitalia, Female / abnormalities
  • Genotype
  • Gonadal Dysgenesis, 46,XY / complications*
  • Gonadal Dysgenesis, 46,XY / genetics*
  • Gonads / abnormalities
  • Humans
  • Karyotyping
  • Middle Aged
  • Neural Conduction / genetics
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology*
  • Peripheral Nerves / physiopathology
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / pathology*
  • Peripheral Nervous System Diseases / physiopathology
  • Sex Differentiation / genetics
  • Sural Nerve / metabolism
  • Sural Nerve / pathology
  • Sural Nerve / physiopathology
  • Wallerian Degeneration / genetics
  • Wallerian Degeneration / pathology
  • Wallerian Degeneration / physiopathology