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A filamin A splice mutation resulting in a syndrome of facial dysmorphism, periventricular nodular heterotopia, and severe constipation reminiscent of cerebro-fronto-facial syndrome
  1. U Hehr1,
  2. A Hehr1,
  3. G Uyanik2,
  4. E Phelan3,
  5. J Winkler2,
  6. W Reardon3
  1. 1Center for Human Genetics, Regensburg, Germany
  2. 2Department of Neurology, University of Regensburg, Germany
  3. 3Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland
  1. Correspondence to:
 Dr Ute Hehr
 Center for Human Genetics, am Universitätsklinikum, D3, Franz-Josef-Strauss-Allee II, 93053 Regensburg, Germany; ute.hehr{at}


Background: Mutations of the filamin A locus (FLNA) on Xq28 have been established in girls with periventricular nodular heterotopia and in patients with otopalatodigital and overlapping phenotypes, the pathogenesis of these phenotypes being thought to be quite distinct. To date only six male cases of periventricular nodular heterotopia (PVNH) have been reported and these almost invariably associated with severe neurological signs.

Methods and Results: We report a new phenotype of male PVNH, with relatively normal development, no epilepsy or other neurological abnormality, severe constipation, and facial dysmorphism and without a discernible skeletal phenotype. This phenotype is associated with a splice site mutation in FLNA c.1923C>T, resulting in the generation of both normal and aberrant mRNA.

Conclusions: We postulate that the patient retains enough FLNA function to avoid the usual lethality associated with loss of function mutations in males and suggest that the severe constipation may be a clue to the molecular aetiology of other X linked conditions associated with severe constipation.

  • FLNA, filamin A gene
  • FMD, frontometaphyseal dysplasia
  • MNS, Melnick-Needles syndrome
  • OPD1, otopalatodigital syndrome type 1
  • OPD2, otopalatodigital syndrome type 2
  • PVNH, periventricular nodular heterotopia
  • cerebro-fronto-facial syndrome
  • constipation
  • filamin A
  • Hirschsprung disease
  • periventricular nodular heterotopia
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  • Published Online First 18 November 2005

  • Dr Reardon wishes to acknowledge support from the Children’s Medical and Research Foundation for his work

  • Competing interests: none declared

  • Patient details are published with consent

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