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Paternal inheritance of classic X‐linked bilateral periventricular nodular heterotopia
Author(s) -
Kasper Burkhard S.,
Kurzbuch Katrin,
Chang Bernard S.,
Pauli Elisabeth,
Hamer Hajo M.,
Winkler Jürgen,
Hehr Ute
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35917
Subject(s) - flna , filamin , germline , genetics , germline mosaicism , germline mutation , missense mutation , biology , disease , mutation , medicine , pathology , gene , cytoskeleton , cell
Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X‐linked dominant inherited, caused by mutations in the Filamin A gene ( FLNA ) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA ‐associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X‐linked dominant traits like FLNA ‐associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA‐ associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X‐linked dominant inherited FLNA ‐associated PNH. © 2013 Wiley Periodicals, Inc.