Emery-Dreifuss muscular dystrophy and familial partial lipodystrophy, Dunnigan variety due to heterozygous LMNA variants.
LMNA variants cause overlapping familial partial lipodystrophy and Emery-Dreifuss muscular dystrophy in 5 families
Emery-Dreifuss muscular dystrophy and familial partial lipodystrophy, Dunnigan variety due to heterozygous LMNA variants.
Specific heterozygous pathogenic variants in LMNA have been reported in patients with Dunnigan-type familial partial lipodystrophy (FPLD2), while other variants cause autosomal dominant Emery-Dreifuss muscular dystrophy (autosomal dominant Emery-Dreifuss muscular dystrophy).
To report the overlapping phenotype of both FPLD2 and autosomal dominant Emery-Dreifuss muscular dystrophy in 5 families with heterozygous LMNA variants.
Clinical, anthropometric, laboratory, and genotyping data of affected subjects from 5 families with female probands presenting with FPLD2 and autosomal dominant Emery-Dreifuss muscular dystrophy phenotypes were collected.
Affected individuals (8 females, ages 18-57 years; 3 males, ages 25-41 years) harbored heterozygous p.
Five females and 2 males had joint contractures and proximal muscle weakness, and 4 females and 1 male had pacemaker-defibrillator implantation for cardiac arrhythmias, confirming autosomal dominant Emery-Dreifuss muscular dystrophy.
Subcutaneous fat loss from the extremities confirming FPLD2 was observed in all females but only in 2 males.
Four females had diabetes mellitus and hypertriglyceridemia, and 1 male had hypertriglyceridemia.
Our report brings attention to the frequent co-occurrence of FPLD2 and autosomal dominant Emery-Dreifuss muscular dystrophy.
In the future, all patients with autosomal dominant Emery-Dreifuss muscular dystrophy should be carefully evaluated for clinical signs of lipodystrophy and metabolic complications.