Neuropediatrics 2008; 39 - P90
DOI: 10.1055/s-2008-1079583

A novel homozygous LMNA mutation (R471C) is associated with a complex phenotype combining mandibuloacral dysplasia, rigid spine muscular dystrophy, and progeria

A Hahn 1, W Kress 2, T Grimm 2, LD Berthold 1, B Neubauer 1, K Kuchelmeister 1, U Müller 1, B Zirn 1
  • 1Justus-Liebig- Universität Gießen, Neuropädiatrie und Sozialpädiatrie, Gießen (D)
  • 2Universität, Würzburg (D)

Laminopathies are a heterogeneous group of 11 distinct disorders that all originate from homozygous or heterozygous mutations in the LMNA gene on chromosome 1q21. We report a 7 year old girl with a new phenotype combining mandibuloacral dysplasia (MAD), progeria, and rigid spine muscular dystrophy. Mild proximal weakness, asymmetrical contractures, rigidity of the spine, and CK-elevation were the initial main findings that led to the diagnosis of congenital muscular dystrophy at age 3 years. Dysmorphic symptoms typical for MAD such as microstomia with hypoplastic mandibula, shortened distal phalanges with acroosteolysis, and type A lipodystrophy, as well as progeroid features became more prominent with time. This allowed delineation of the full phenotype not before school age. The girl's phenotype was caused by a homozygous mutation in the LMNA gene (c.1411C>T, p.R471C) that was inherited from the heterozygous (consanguineous) healthy parents. Until now, this mutation has only been reported in compound heterozygous state and associated with much milder clinical symptoms. Autosomal-recessive LMNA mutations are known to cause Emery-Dreyfuss muscular dystrophy, MAD, and MAD with overlapping phenotypes („MAD spectrum“). The reported homozygous LMNA mutation R471C results in the severest phenotype of the „MAD spectrum“ recognized to date. This case further expands the phenotypic range of lamin A/C associated diseases and widens the clinical spectrum of MAD. Exact delineation of the phenotype is important for correct monitoring and timely treatment of potential complications associated with specific LMNA mutations.