Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families:Case report

• Published in: Human reproduction (Oxford) Vol. 20; no. 8; pp. 2173 - 2178
• Main Authors: Sato, Naoko, Hasegawa, Tomonobu, Hori, Naoaki, Fukami, Maki, Yoshimura, Yasunori, Ogata, Tsutomu
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2005; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Child; Family Health; Female; fertility; FGFR1 mutation; Genetic Counseling; genetic counselling; gonadotrophin therapy; Gonadotropins - therapeutic use; Gynecology. Andrology. Obstetrics; Heterozygote; Humans; Infertility - drug therapy; Infertility - genetics; Kallmann syndrome; Kallmann Syndrome - complications; Kallmann Syndrome - drug therapy; Kallmann Syndrome - genetics; Male; Medical sciences; Pedigree; Point Mutation; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Fibroblast Growth Factor - genetics; mutation; genetic counselling; gonadotrophin therapy; Kallmann syndrome; fertility; Endocrinopathy; Human; Hypogonadotropic hypogonadism; Fibroblast growth factor; Nervous system diseases; Hypothalamic diseases; Gonadotropin; Genital diseases; Cerebral disorder; Genetic disease; Case study; Vertebrata; Growth factor receptor; Genetic counseling; Mammalia; Treatment; Malformation; Fertility; Central nervous system disease; ENT disease; fertility/FGFR1 mutation/genetic counselling/gonadotrophin therapy/Kallmann syndrome; Mutation
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/dei052

Gonadotrophin therapy (GT) is frequently used to induce fertility in Kallmann syndrome (KS). We studied the effects and the consequences of GT in autosomal dominant KS caused by heterozygous FGFR1 mutations. Three Japanese families were examined. In family A, an adult male received GT and had two sons. In family B, an adult female received GT and gave birth to dizygotic male and female twins. In family C, an adult female received GT and produced a son and a daughter. Direct sequencing was performed for FGFR1, and clinical assessment was carried out for KS features. The father and the elder son of family A had P745S mutation, the mother and the female twin of family B had G687R mutation, and the mother and the two children of family C had S107X mutation. KS phenotype was detected for the mutation-positive subjects, except for the elder son of family A who had apparently normal phenotype. GT in FGFR1 mutations is effective in acquiring fertility but has a risk of transmitting the mutation and the disease phenotype to the next generation.