Juvenile muscular atrophy of the distal upper extremities associated with x-linked periventricular heterotopia with features of Ehlers-Danlos syndrome

Muscle Nerve. 2016 Oct;54(4):794-7. doi: 10.1002/mus.25175. Epub 2016 May 27.


Introduction: Juvenile muscular atrophy of the distal upper extremities (JMADUE) is a rare, sporadic disorder that affects adolescent males and is characterized by progressive but self-limited weakness of the distal upper extremities. The etiology is unknown, but cervical hyperflexion has been hypothesized.

Methods: We report a case of an adolescent male who presented with typical JMADUE but also had joint hypermobility and multiple congenital anomalies, including periventricular heterotopias, suggesting a multisystem syndrome.

Results: Subsequent diagnostic testing confirmed a diagnosis of JMADUE, and sequencing of the filamin-A gene showed a novel, pathogenic mutation that confirmed an additional diagnosis of X-linked periventricular heterotopias with features of Ehlers-Danlos syndrome (XLPH-EDS).

Conclusions: The concurrent diagnosis of these 2 rare conditions suggests a pathogenic connection. It is likely that the joint hypermobility from XLPH-EDS predisposed this patient to developing JMADUE. This supports the cervical hyperflexion theory of pathogenesis. This case also expands the phenotype associated with FLNA mutations. Muscle Nerve 54: 794-797, 2016.

Keywords: Ehlers-Danlos syndrome; Filamin-A; Hirayama disease; cervical hyperflexion; distal upper extremities; juvenile muscular atrophy; periventricular heterotopias.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / diagnostic imaging
  • Abnormalities, Multiple / physiopathology
  • Adolescent
  • Ehlers-Danlos Syndrome / complications
  • Ehlers-Danlos Syndrome / diagnostic imaging*
  • Ehlers-Danlos Syndrome / physiopathology
  • Humans
  • Male
  • Periventricular Nodular Heterotopia / complications
  • Periventricular Nodular Heterotopia / diagnostic imaging*
  • Periventricular Nodular Heterotopia / physiopathology
  • Spinal Muscular Atrophies of Childhood / complications
  • Spinal Muscular Atrophies of Childhood / diagnostic imaging*
  • Spinal Muscular Atrophies of Childhood / physiopathology
  • Upper Extremity / diagnostic imaging*
  • Upper Extremity / physiopathology