G.P.150: Clinical heterogeneity in adult forms of FHL1 related myopathies. The “Institut de Myologie” experience

Abstract

FHL1 gene mutations are responsible for reducing body myopathy (RBM), a rare condition characterized by progressive muscle weakness and the presence of intracytoplasmic aggregates. Age at onset ranges from early onset in infancy, through childhood and in some cases adult age. FHL1 mutations may also lead to allelic disorders including Emery-Dreifuss like muscular dystrophy (EDMD), hypertrophic cardiomyopathy (HCM), X-linked myopathy with postural muscle atrophy and generalized hypertrophy (X-MPMA) and X-linked scapuloperoneal myopathy (X-SM). To report clinical, muscle imaging, histological and genetic features found of adult patients carrying FHL1 mutations, we retrospectively reviewed their medical reports of the 11 patients (6 M, 5 F) belonging to 8 families followed at the “Institute de Myologie”, Pitie-Salpetriere hospital, Paris. The 11 patients were assessed from 13 to 52 years old. Pseudodominant mode of inheritance was suggested in 4 families, X-linked in 3 and sporadic in one. Four had EDMD, 2 X-SM, 1 X-MPMA, 1 HCM while 2 patients had atypical features and 1 was still asymptomatic. When symptomatic, female patients had a striking asymmetric muscle involvement. Five patients had hypertrophic cardiomyopathy requiring heart transplantation in one patient at 18 years old. Two patients required night time ventilation due to diaphragm paralysis. Histologically, only 3 patients among the 8 probands had reducing bodies (RBs) at muscle biopsy, while 3 had non specific pattern, 1 had neuropathic pattern and one muscle biopsy was considered as normal. In contrast to infantile forms of FHL1 related myopathy that usually show RBs at muscle biopsy and lead to early death, adult forms had wider clinical and histological presentations. Moreover, FHL1 gene screening should be considered in those undiagnosed patients suffering from myopathies with diaphragm paralysis and/or HCM where X-linked inheritance is not excluded even in the absence of RBs at muscle pathology.