Probably Norrie's disease due to mutation. Two sporadic sibships of two males each, a necropsy of one case, and, given Norrie's disease, a calculation of the gene mutation frequency.
Two sibships, each with two affected males but no other affected family members, are described. All four patients at birth had small eyes with white masses visible behind clear lenses. Support for a diagnosis of Norrie's disease lies in the probable mental retardation and sudden death of one child and mental retardation in the other in one of the families, and strong support in the sensorineural deafness in one child in the other family. A necropsy was performed on the dead child. Both eyes showed the retinae to be totally non-attached. The optic nerves were thin. If the diagnosis is Norrie's disease (highly probable), the birth of the second affected child in each family supports the postulate of a mutation in the X chromosome of a germ cell of a maternal grandparent or an earlier maternal ancestor, no previous member of the family having been affected. That implies a 50% risk of the disease in future male siblings and a 50% risk of the carrier state in female sibs. When only one child is affected, the explanation could also be a mutation in that individual. Given Norrie's disease, we have calculated a mutation rate of 3.9 per million chromosomes in the Scottish population--remarkably similar to the mutation rates calculated for many dominant diseases. A diagnosis of autosomal recessive non-attachment of retina implies a 25% risk to later siblings.
D001766:Blindness / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D003638:Deafness / Q000235:genetics*; D005123:Eye / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D009900:Optic Nerve / Q000473:pathology; D010375:Pedigree; D013577:Syndrome; D014960:X Chromosome