Leyten et al. (1995) described 2 sisters with severe psychomotor retardation and generalized muscle weakness involving the face as well as the axial and limb mus...
Leyten et al. (1995) described 2 sisters with severe psychomotor retardation and generalized muscle weakness involving the face as well as the axial and limb musculature, present within the first months of life. Serial muscle biopsy showed progressive infiltration with fat cells, as well as variable expression of merosin (156225). Scanning of the cerebrum demonstrated ventriculomegaly and severe cerebral and cerebellar atrophy, as well as hypomyelination. EMG demonstrated myopathic potentials and markedly decreased motor nerve conduction velocities (25 meters per second in the median nerve). Central evoked potentials were isoelectric. Postmortem examination demonstrated marked atrophy of the brain with a weight of 225 grams at 30 months. Gray and white matter were poorly delineated. There was replacement gliosis in the cerebral cortex and diffuse lack of myelinated fibers in the subcortical white matter. Sural nerve biopsy demonstrated almost complete absence of large diameter fibers but no signs of degeneration, suggesting to Leyten et al. (1995) a defect of maturation. The severe brain and sural nerve pathology differed from those previously described in conjunction with congenital muscular dystrophy. Lack of clinical or electromyographic abnormalities in the parents suggested autosomal recessive inheritance.
Seidahmed et al. (1996) reported 2 sisters, born of first-cousin parents, who were born with severe hypotonia, arthrogryposis multiplex congenita, and dysmorphic features consistent with the fetal akinesia/hypokinesia sequence. Both needed assisted ventilation and died at the age of 5 months. Both had type II lissencephaly (cobblestone lissencephaly), which was visualized by MRI in the proband. Ophthalmic evaluation showed no ocular malformations in either of them. Brain auditory-evoked potentials revealed bilateral severe sensorineural hearing loss in the proband, whereas an MRI-guided open muscle biopsy of the sartorius muscle (the only remaining thigh muscle) showed features of muscular dystrophy. Immunohistochemistry revealed normal dystrophin, dystrophin-associated glycoproteins, and merosin.
Sztriha et al. (1999) described 2 infants, born in an inbred Arab family, with a syndrome of micrencephaly with simplified gyral pattern, abnormal myelin formation, and arthrogryposis. Increased variation of fiber size was seen in the muscle biopsy; creatine kinase, however, was normal. Large areas of muscle were replaced by adipofibrous tissue. The infants had dysmorphic features consistent with the fetal akinesia/hypokinesia sequence.