Abstract Kallmann syndrome (KS) is a rare pediatric disease with major manifestations of olfactory dysfunction and hypogonadotropic hypogonadism. Five children (4 boys and 1 girl) with KS reported in this article were aged between 6 months and 19 years at the time when they attended the hospital. All the children had the clinical manifestation of hypogonadotropic hypogonadism; in addition, three children had olfactory dysfunction (two were found to have olfactory bulb dysplasia on magnetic resonance imaging), one had cleft lip and palate, and one had micropenis and cryptorchidism with right renal agenesis during infancy. All the five children had normal karyotype and their parents had normal clinical phenotypes. The uncle of one child had underdeveloped secondary sexual characteristics and olfactory disorder since childhood. High-throughput sequencing found two known heterozygous missense mutations in the FGFR1 gene, i.e., c.1097C > T(p.P366L) and c.809G > C(p.G270A), in two children. One child had a novel frameshift mutation, c.1877_1887/p.S627Tfs*6, in the KAL1 gene; this deletion mutation caused a frameshift in base sequence and produced truncated proteins, which led to a significant change in protein structure, and thus it was highly pathogenic. It is concluded that KS has great clinical and genetic heterogeneity and can be accompanied by incomplete dominant inheritance and that gene detection helps with the diagnosis of this disease.
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