title: Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1).
abstract: Kallmann syndrome characterised by hypogonadotropic hypogonadism (HH) and anosmia is genetically heterogeneous with X-linked, autosomal dominant and autosomal recessive forms. The autosomal dominant form due to loss of function mutation in the fibroblast growth factor receptor 1 (FGFR1) accounts for about 10% of cases. We report here three paediatric cases of Kallmann syndrome with unusual phenotype in two unrelated patients with severe ear anomalies (hypoplasia or agenesis of external ear) associated with classical features, such as cleft palate, dental agenesis, syndactylia, micropenis and cryptorchidism. We found de novo mutation in these two patients (Cys178Ser and Arg622Gly, respectively), and one inherited Arg622Gln mutation with intrafamilial variable phenotype. These genotype-phenotype correlations indicate that paediatric phenotypic expression of FGFR1 loss of function mutations is highly variable, the severity of the oro-facial malformations at birth does not predict gonadotropic function at the puberty and that de novo mutations of FGFR1 are relatively frequent.
authors.affiliation: Assistance Publique Hôpitaux de Paris, Robert Debre Hospital Paediatric Endocrinology unit, Robert Debré Hospital, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Zenaty
authors.forename: Patricia
authors.initials: P
authors.lastname: Bretones
authors.forename: Cécile
authors.initials: C
authors.lastname: Lambe
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guemas
authors.forename: Michel
authors.initials: M
authors.lastname: David
authors.forename: Juliane
authors.initials: J
authors.lastname: Léger
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Roux
mesh_terms: D000293:Adolescent; D002972:Cleft Palate / Q000235:genetics; D003456:Cryptorchidism / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000151:congenital; D003744:Dental Enamel Hypoplasia / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D005837:Genitalia, Male / Q000002:abnormalities; D006801:Humans; D007223:Infant; D017436:Kallmann Syndrome / Q000235:genetics*; D007621:Karyotyping; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009154:Mutation; D000857:Olfaction Disorders / Q000151:congenital; D009830:Olfactory Bulb / Q000002:abnormalities; D010375:Pedigree; D010641:Phenotype; D011628:Puberty, Delayed / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D013576:Syndactyly / Q000235:genetics; D046608:Synkinesis / Q000151:congenital; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1