The clinical, biological, and molecular genetic aspects of Kallmann syndrome are reported from the Institute of Molecular Genetics, Baylor College of Medicine, Houston, TX. Kallmann syndrome, first described in 1944, is characterized by familial hypogonadism and anosmia associated with aplasia of olfactory bulbs and tracts. Additional neurologic signs include synkinesia, eye movement abnormalities, horizontal nystagmus, cerebellar ataxia, sensorineural deafness, spastic paraplegia, spatial attention deficits, and mental retardation. Somatic defects including pes cavus, unilateral renal agenesis, and cleft lip and palate are also described. A predominantly X-linked inheritance is reflected in a fivefold excess of male (1 in 10 000) over female (1 in 50 000) patients, and the occurrence of both autosomal dominant and recessive forms indicates genetic heterogeneity. Diagnosis is made at puberty because of a delay in secondary sex characteristics, a eunuchoid habitus, gynecomastia, micropenis, and cryptorchidism. Isolation of the KAL gene responsible for the X-linked form of the disease points to a molecular basis for a neuronal migration defect affecting olfactory axons as the primary cause of Kallmann syndrome. 
COMMENT. An adolescent male of eunuchoid build, referred to the neurologist because of attention, coordination and other deficits, should be considered for olfactory tests and an MRI of the olfactory system. Genetics of Kallmann syndrome, see Martin JB.