CHD7 mutations in patients initially diagnosed with Kallmann syndrome – the clinical overlap with CHARGE syndrome |
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| Authors: | MCJ Jongmans CMA van Ravenswaaij-Arts N Pitteloud T Ogata N Sato HL Claahsen-van der Grinten K van der Donk S Seminara JEH Bergman HG Brunner WF Crowley Jr LH Hoefsloot |
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| Affiliation: | Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;, Department of Genetics, University Medical Center Groningen, Groningen University, The Netherlands;, Harvard Reproductive Endocrine Sciences Center and The Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;, Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan;, and Department of Pediatric Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands |
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| Abstract: | Kallmann syndrome (KS) is the combination of hypogonadotropic hypogonadism and anosmia or hyposmia, two features that are also frequently present in CHARGE syndrome. CHARGE syndrome is caused by mutations in the CHD7 gene. We performed analysis of CHD7 in 36 patients with KS and 20 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) in whom mutations in KAL1 , FGFR1 , PROK2 and PROKR2 genes were excluded. Three of 56 KS/nIHH patients had de novo mutations in CHD7 . In retrospect, these three CHD7 -positive patients showed additional features that are seen in CHARGE syndrome. CHD7 mutations can be present in KS patients who have additional features that are part of the CHARGE syndrome phenotype. We did not find mutations in patients with isolated KS. These findings imply that patients diagnosed with hypogonadotropic hypogonadism and anosmia should be screened for clinical features consistent with CHARGE syndrome. If such features are present, particularly deafness, dysmorphic ears and/or hypoplasia or aplasia of the semicircular canals, CHD7 sequencing is recommended. |
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| Keywords: | anosmia CHARGE syndrome CHD7 gene hypogonadotropic hypogonadism Kallmann syndrome |
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