P.48 - Novel compound heterozygous mutations in PLEC gene causing epidermolysis bullosa simplex with muscular dystrophy, case series of two affected sisters

Abstract

Epidermolysis bullosa simplex with muscular dystrophy (EBSMD) is a rare clinical entity characterized by childhood onset of progressive muscular dystrophy and blistering skin changes. It is caused by homozygous or compound heterozygous mutations in the plectin gene (PLEC). Genetic defects have been reported in a limited number of patients. The precise phenotype-genotype correlations have yet to be defined. Here we describe two affected sisters with detailed clinical presentation, exam findings including timed motor function tests, MRI images and results, and confirmed novel PLEC compound heterozygous mutations. CASE SERIES: #1 Five-year-old female born premature at 25 weeks was evaluated for motor delay. Epidermolysis bullosa (EB) was diagnosed at age 5 months with recurrent skin blisters. She sat alone at 18 months, walked at 2 years of age and never could jump with both feet. Physical exam revealed small stature and dysmorphic findings including micrognathia, high-arched palate, poor dentition with erosions, hand and foot blisters and nail deformation. Neurological examination showed generalized muscle weakness, decreased reflexes and delayed time-with-sit-to-stand, 30-feet-run, and 4-steps-climbing. CPK was elevated at 519 unit/L. Muscle MRI showed asymmetric atrophy of the quadriceps muscles, mild fatty infiltration in the quadriceps and gluteus maximus muscles and subtle increased T2 signal in the quadriceps muscles bilaterally. Genetic testing confirmed heterozygous mutations in PLEC (c.11912delA and c.6276dupA) causing frame shift stacking leading to premature stop codons. #2 Three-year-old sister was also diagnosed with EB was found to have same heterozygous PLEC mutations. She had delayed motor development and elevated CPK level. Muscle MRI was unremarkable. We presented clinical evidence that the novel compound heterozygous PLEC mutations are pathogenic for EBSMD.