Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review
Open accessAbstract
Kallmann syndrome (KS) describes the association of isolated hypogonadotropic hypogonadism with hypo/anosmia. A few KS patients may reverse hypogonadism after testosterone withdrawal, a variant known as reversible KS. Herein, we describe the first mutation in KAL1 in a patient with reversible KS and review the literature. The proband was first seen at 22 years complaining of anosmia and lack of puberty. His brother had puberty at 30 years and a maternal granduncle had anosmia and delayed puberty. On physical examination, he was P 2 G 1, testes were 3 ml and bone age was 14 years. During 20 years of irregular testosterone replacement, he developed secondary sexual characteristics and testicular enlargement. At the age of 41 years, after stopping testosterone replacement for 5 months, his testes were 15 ml, serum testosterone, LH, and FSH responses to GnRH were normal, and his wife was pregnant. The molecular study revealed a cytosine insertion in exon 2 of KAL1, generating a frameshift at codon 75 and a premature stop at codon 85. The expected gene product is a truncated peptide with 85 of the 610 amino acids present in the wild-type protein. Fourteen cases of reversible KS have been described but the genotype was only studied in a single case showing a heterozygous fibroblast growth factor receptor type 1 (FGFR1) mutation. Considering the low prevalence of mutations in KAL1 or FGFR1 in KS, it is possible that these genotypes are more prevalent in reversible KS than in other KS patients, but additional studies are necessary to confirm this hypothesis.
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- Authors
- Ribeiro, R. S., Vieira, T. C., & Abucham, J.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03
- Volume
- 156
- Issue
- 3
- Pages
- 285-290
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2140152963
- Cited by
- 71
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 9 · 2012: 7
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- hypogonadotropic hypogonadism, anosmia, delayed puberty, testosterone withdrawal, testosterone replacement therapy, frameshift mutation, FGFR1 mutation, GnRH response, testicular enlargement
- MeSH terms
- Adult, Base Sequence, DNA Mutational Analysis, Humans, Male, Mutation, Nerve Tissue Proteins, Mutagenesis, Insertional, Extracellular Matrix Proteins, Frameshift Mutation, Kallmann Syndrome
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