Stephen G. Ryan

Mutations in the α1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia

Hereditary hyperekplexia, or familial startle disease (STHE), is an autosomal dominant neurologic disorder characterized by marked muscle rigidity of central nervous system origin and an exaggerated startle response to unexpected acoustic or tactile stimuli. Linkage analyses in several large families provided evidence for locus homogeneity and showed the disease gene was linked to DNA markers on the long arm of chromosome 5. Here we describe the identification of point mutations in the gene encoding the α1 subunit of the glycine receptor (GLRA1) in STHE patients from four different families. All mutations occur in the same base pair of exon 6 and result in the substitution of an uncharged amino acid (leucine or glutamine) for Arg271 in the mature protein.

Spontaneous regression of optic glioma in a patient with neurofibromatosis

We describe a young girl with neurofibromatosis and enlargement of the optic chiasm and intracranial left optic nerve. Serial MRIs over 32 months demonstrated spontaneous, marked reduction in the size of these lesions. Spontaneous regression must be considered in evaluating therapies for optic glioma.

Paroxysmal Kinesigenic Dystonia After Methylphenidate Administration

We report a patient who developed paroxysmal kinesigenic dystonia shortly after initiation of therapy with methylphenidate for presumed attention deficit-hyperactivity disorder. Attacks persisted long after methylphenidate was discontinued and responded completely to treatment with carbamazepine. Though it is possible that methylphenidate caused this syndrome in our patient, it is more likely that the stimulant triggered the onset of a genetically determined disorder. (J Child Neurol 1994;9:45-46).

An autosomal recessive form of benign familial neonatal seizures

We present a consanguineous sibship with benign familial neonatal seizures. The mode of transmission of the disorder in this family seems to be autosomal recessive, which is contrary to the usual autösomal dominant type. Linkage analysis failed to show tight linkage between the disease locus and the autosomal dominant locus assigned to chromosome 20q. We thus conclude that benign familial neonatal seizures is a genetically heterogeneous type of epilepsy.

Evidence of a third locus for benign familial convulsions

Two autosomal dominant forms of benign idiopathic epilepsy of early life have been described: benign neonatal familial convulsions and benign infantile familial convulsions. Herein we describe a pedigree with familial convulsions in which the age of onset is intermediate between that seen in these two disorders. Two genes responsible for benign neonatal familial convulsions have been mapped to chromosome 20q and to chromosome 8q. Previously, the chromosome 20q benign neonatal familial convulsions locus had been excluded in this pedigree. Further linkage analysis in our laboratory revealed that the chromosome 8 benign neonatal familial convulsions locus also is not responsible for seizures in this pedigree. These results indicate that there are at least three loci responsible for autosomal dominant benign epilepsies of early life. ( J Child Neurol 1996;11:211-214).