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

• Published in: American journal of medical genetics. Part A Vol. 146A; no. 8; pp. 1049 - 1054
• Main Authors: Zirn, Birgit, Kress, Wolfram, Grimm, Tiemo, Berthold, Lars Daniel, Neubauer, Bernd, Kuchelmeister, Klaus, Müller, Ulrich, Hahn, Andreas
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.04.2008; Wiley-Liss
• Subjects: Biological and medical sciences; Child; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - physiopathology; Diseases of striated muscles. Neuromuscular diseases; Female; Homozygote; Humans; Lamin Type A - genetics; LMNA; mandibuloacral dysplasia; Medical genetics; Medical sciences; Muscular Dystrophies - genetics; Muscular Dystrophies - physiopathology; muscular dystrophy; Mutation; Neurology; Phenotype; progeria; Progeria - physiopathology; spinal rigidity; Spine - abnormalities; Skin disease; Nervous system diseases; Neuromuscular diseases; Dysplasia; mandibuloacral dysplasia; Spine; Homozygosity; Muscular dystrophy; Genetic disease; Dwarfism; Phenotype; Association; Progeria; LMNA; Mutation; spinal rigidity
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32259

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. © 2008 Wiley‐Liss, Inc.