Two unrelated young women presented with similar dysmorphic features including severe
retrognathia, beaked nose, narrow chest, sloping shoulders, and an acrogeric appearance of the hands and feet. Neither had any evidence of skeletal
myopathy, but both developed progressive
dilated cardiomyopathy, both experienced
premature ovarian failure, and both were found to have the same heterozygous novel missense mutation c.176T>G in exon 1 of the LMNA gene, resulting in a
leucine to
arginine change at
codon 59 (Leu59Arg). Mutations in the LMNA gene cause a variety of disorders including
dilated cardiomyopathy,
muscular dystrophy, familial
lipodystrophy,
progeria, atypical progeroid syndromes, and mandibuloacral dysplasia. Genotype-phenotype correlation has been reported for some of these conditions. Our patients are the only ones known to have the specific mutation Leu59Arg and also share a set of features not entirely consistent with any of the
laminopathies previously described. A previously reported patient with an adjacent mutation (Ala57Pro) had "atypical
Werner syndrome" with
dilated cardiomyopathy,
hypogonadism, and sloping shoulders. While each of these clinical features does occur in other
laminopathy syndromes, these patients form a phenotypic cluster distinct from other
laminopathies and clinically overlapping with
Malouf syndrome. LMNA sequencing should be considered for patients presenting with
dilated cardiomyopathy and
hypergonadotropic hypogonadism, including those previously diagnosed with
Malouf syndrome.