Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.

ABSTRACT

We report on a 7-year-old girl with a phenotype combining mandibuloacral dysplasia (MAD), progeria, and rigid spine muscular dystrophy. Mild proximal weakness, contractures, and rigidity of the spine were the primary findings. Although present since birth, dysmorphic manifestations typical for MAD and progeroid features became more prominent with time, and the full clinical phenotype was recognizable at early school age. Her phenotype was caused by a homozygous mutation in LMNA (c.1411C > T, which predicts p.R471C) inherited from the heterozygous, consanguineous, unaffected parents. This mutation has only been reported in compound heterozygous state and was associated with a milder phenotype. Some LMNA mutations are known to cause MAD and overlapping phenotypes (MAD spectrum) in an autosomal recessive pattern. The p.R471C homozygous LMNA mutation causes a severe phenotype of the MAD spectrum. This case extends the clinical spectrum of MAD and further expands the phenotypic range of lamin A/C associated diseases.