Roll et al. (2006) described a 3-generation French family with oral and speech dyspraxia, rolandic seizures, and mental retardation. The proband, a right-handed girl, lacked language at age 2.5 years when diurnal and nocturnal rolandic seizures started. Neurologic ... Roll et al. (2006) described a 3-generation French family with oral and speech dyspraxia, rolandic seizures, and mental retardation. The proband, a right-handed girl, lacked language at age 2.5 years when diurnal and nocturnal rolandic seizures started. Neurologic examination at age 10 years showed orofacial dyspraxia and severe speech delay. The proband's younger half-brother also had a history of epileptic seizures with speech impairment. A total of 8 individuals in 3 generations had oral and speech dyspraxia, rolandic seizures, and mental retardation; 3 individuals had mental retardation with oral and speech dyspraxia, without seizures. Roll et al. (2006) also described a 12-year-old boy who presented with focal seizures beginning with numbness of the fingers of the right hand and leg and a sudden fall. Other attacks began with twitching of the right side of the mouth, drooling, and loss of awareness. He was left-handed. Neurologic examination revealed clonus at both knees and generalized hyperreflexia with an equivocal right plantar response. Neuropsychologic examination at age 15 years showed low average to average intellect with weakness in mathematical ability. His EEG showed left centrotemporal epileptiform activity with a rolandic horizontal dipole. MRI showed bilateral posterior perisylvian polymicrogyria (300388), more severe on the left and extending back to involve the parietooccipital regions. Two of his maternal aunts had mild mental retardation, and his mother and another aunt were of normal intelligence.
Roll et al. (2006) identified a mutation in the SRPX2 gene (N327S; 300642.0001) on Xq22 as being responsible for rolandic seizures associated with oral and speech dyspraxia and mental retardation in a 3-generation French family. SRPX2 is a ... Roll et al. (2006) identified a mutation in the SRPX2 gene (N327S; 300642.0001) on Xq22 as being responsible for rolandic seizures associated with oral and speech dyspraxia and mental retardation in a 3-generation French family. SRPX2 is a secreted sushi repeat-containing protein expressed in neurons of the human adult brain, including the rolandic area. The disease-causing mutation resulted in gain of glycosylation of the secreted mutant protein. A second mutation (300642.0002) was identified within the first sushi domain of SRPX2 in a male with rolandic seizures and bilateral perisylvian polymicrogyria and in his female relatives with mild mental retardation or unaffected carrier status. The authors suggested that SRPX2 may play an important role in the development and/or function of the perisylvian region critical for language and cognitive development. In the French family reported by Roll et al. (2006), Lesca et al. (2013) identified a heterozygous ala716-to-thr (A716T) substitution at a highly conserved residue in the GRIN2A gene (138253) that is associated with focal epilepsy and speech disorder with or without mental retardation (FESD; 245570). All but 2 affected family members with the SRPX2 mutation also carried the GRIN2A mutation. All patients with the GRIN2A mutation had seizures, whereas the 2 patients with only the SRPX2 mutation and not the GRIN2A mutation did not have seizures. It was unclear whether the 2 mutations acted synergistically or independently to affect the phenotype in this family.