Detection of KAL-1 gene deletion with fluorescence in situ hybridization

We investigated the molecular cytogenetic status of two unrelated boys and their family members because they had features consistent with Kallmann syndrome but normal karyotypes. The first patient was a 6-year-old boy who suffered from ichthyosis, bilateral cryptorchidism, hyposmia, and neurologic disorders including mirror movements of the hands and nystagmus. Mild to moderate mental retardation was also noted in this boy, his mother, and maternal grandmother. Fluorescence in situ hybridization (FISH) study using probes for Kallmann (KAL), steroid sulfatase, and ocular albinism type 1 all showed nullisomy on Xp22.3 in this patient, and hemizygosity in his older sister, mother, and maternal grandmother. The second patient was a 1-year-old boy who had micropenis, cryptorchidism, and hypoplastic scrotum since birth. Family study disclosed a 28-year-old maternal uncle with cryptorchidism, lack of secondary sexual characteristics, and anosmia. FISH showed only the KAL gene deletion. Polymerase chain reaction analysis also showed an absence of the KAL-1 sequence. FISH is a useful tool for the detection of KAL-1 deletion in people with normal karyotypes but features consistent with Kallmann syndrome.