Fibroblast growth factor receptor 1 (Fgfr1) plays a pivotal role in craniofacial bone development, and loss of Fgfr1 leads to cleft palate and facial cleft defects in newborn mice.
Heterozygous mutations in the FGFR1 gene accompanied by a high frequency of cleft palate and other facial dysmorphisms were recently identified in 8% of a large KS cohort, yet the reproductive phenotype of KS patients harboring FGFR1 mutations has not been described.
Although Kallmann syndrome (KS) caused by heterozygous loss of function mutations of the fibroblast growth factor receptor 1 gene (FGFR1) is occasionally associated with characteristic features, such as dental agenesis and cleft palate, FGFR1 mutations remain unidentified in several KS patients with such characteristic features.
The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.