X chromosome-linked Kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene.
Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the X chromosome-linked form of the disease, KAL-1, consists of 14 coding exons. It encodes a glycoprotein, anosmin-1, which is involved in the embryonic migration of GnRH-synthesizing neurons and the differentiation of the olfactory bulbs. We describe herein the clinical heterogeneity in three affected brothers who carry a large deletion (exons 3-13) in KAL-1. All three had a history of hypogonadotropic hypogonadism with delayed puberty. Although brain magnetic resonance imaging showed hypoplastic olfactory bulbs in the three siblings, variable degrees of anosmia/hyposmia were shown by olfactometry. In addition, these brothers had different phenotypic anomalies, i.e. unilateral renal aplasia (siblings B and C), high-arched palate (sibling A), brachymetacarpia (sibling A), mirror movements (siblings A and B), and abnormal eye movements (sibling C). Last but not least, sibling A suffered from a severe congenital hearing impairment, a feature that had been reported in KS but had not yet been ascribed unambiguously to the X-linked form of the disease. The variable phenotype, both qualitatively and quantitatively, in this family further emphasizes the role of putative modifier genes, and/or epigenetic factors, in the expressivity of the X-linked KS.
Massin
Nathalie
N
Department of Endocrinology and Reproductive Medicine, Hôpital Necker, 75743 Paris Cedex 15, France.
Pêcheux
Christophe
C
Eloit
Corinne
C
Bensimon
Jean-Louis
JL
Galey
Julie
J
Kuttenn
Frédérique
F
Hardelin
Jean-Pierre
JP
Dodé
Catherine
C
Touraine
Philippe
P
D000293:Adolescent; D000328:Adult; D001827:Body Height; D015815:Cell Adhesion Molecules / Q000235:genetics*; D041321:Chromosomes, Human, X; D005091:Exons; D016326:Extracellular Matrix Proteins; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D007006:Hypogonadism; D017436:Kallmann Syndrome / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D000857:Olfaction Disorders; D009830:Olfactory Bulb / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011628:Puberty, Delayed; D012903:Smell
C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins