MALE NEONATAL DEATH AND PROGRESSIVE WEAKNESS AND IMMUNE-DEFICIENCY INFEMALES - AN UNKNOWN X-LINKED CONDITION

We report a family with an undiagnosed X linked condition. The grandmo ther, two of her three daughters, and one of her granddaughters have a slowly progressive proximal weakness, brisk reflexes, poor bladder fu nction, static reduced night vision, and IgG2 deficiency. The diagnosi s of the three living symptomatic females was ''hereditary spastic par aplegia plus''. They have lost five male children who died in the neon atal period of severe hypotonia and were of low birth weight. Investig ations have not led to a unifying diagnosis: myotonic dystrophy, NARP, and X linked hyper IgM were specifically eliminated. Using the hypoth esis that the condition is X linked dominant, haplotype analysis of th e family suggests that the disease locus is within Xq26-qter. This ent ity should be considered in the differential diagnosis of families pre senting with severe neonatal hypotonia in males and females with sympt oms suggestive of complex hereditary spastic paraplegia.