CONGENITAL MUSCULAR DYSTROPHY WITH DEFECTIVE α-DYSTROGLYCAN, CEREBELLAR HYPOPLASIA, AND EPILEPSY

Abstract

Congenital muscular dystrophies (CMDs) with hypoglycosylation of α-dystroglycan (α-DG) are heterogeneous disorders often involving brain, eyes, and muscle. Mutations in 6 known or putative glycosyltransferase genes have been identified: Protein-O-mannosyl transferase 1 ( POMT1 ), Protein-O-mannosyl transferase 2 ( POMT2 ), Protein-O-mannose1,2-N-acetylglucosaminyltransferase 1 , Fukutin , Fukutin-related protein , and LARGE . Mutations in each of these genes have been associated with a wide range of phenotypes ranging from the severe Walker–Warburg syndrome (WWS) to milder variants of limb girdle muscle dystrophy.1 We report 4 cases of CMD with a distinctive phenotype characterized by cognitive impairment, microcephaly, cerebellar hypoplasia, feeding difficulties, and progressive myoclonic epilepsy. Mutations in the 6 known genes were ruled out in these patients. ### Case reports. All 4 patients originated from the same area in Calabria, in Southern Italy. Two were sporadic cases, both girls (patients 1 and 2), and 2 were brothers born to first-degree cousins (patients 3 and 4). Clinical features were similar in all patients. #### Onset. There were reduced fetal movements and weak cry, difficulty in swallowing, severe hypotonia, and muscle weakness at birth. #### Developmental milestones and progression. None acquired head control or any other milestone with the exception of patient 2, who acquired head control at 12 months and sat with support after 18 months for a short period. Cognitive development was severely impaired with absent speech. All patients had microcephaly and myopathic face, generalized muscle wasting, and severe hypotonia. They were able to …