ArticleThe Journal of clinical endocrinology and metabolism2013
Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00494169 (Molecular Basis of Inherited Reproductive Disorders), which is not on this map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Molecular Basis of Inherited Reproductive Disorders
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Tooth agenesis and orofacial clefting: genetic brothers in arms?Human genetics · 2016Pooled it
- Article
- Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026Review
- Reversible congenital hypogonadotropic hypogonadism: keys for clinical management.Archives of endocrinology and metabolism · 2026Review
- Pleiotropic genes linking congenital hypogonadotropic hypogonadism and cleft lip/palate: evidence from a genomic CHH cohort study.European journal of human genetics : EJHG · 2026Article
- Haploinsufficiency of Sox2 causes fewer GnRH neurons and delayed puberty in mice.Endocrinology · 2026Article
- De novo rare EMX2 variants lead to idiopathic hypogonadotropic hypogonadism.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Expanded Targeted-Exome Sequencing and Functional Validation Improve Molecular Diagnosis and Refine Genotype-Phenotype Correlations in Congenital Hypogonadotropic Hypogonadism.Neuroendocrinology · 2026Article
- Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism.Annals of the New York Academy of Sciences · 2024Review
- Genetic Variability ofMolecular syndromology · 2024Article
- Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations.Asian journal of andrology · 2024Article
- The multifaceted links between hearing loss and chronic kidney disease.Nature reviews. Nephrology · 2024Review
- Additional mutation inBMJ case reports · 2024Article
- [Research progress on hereditary endocrine and metabolic diseases associated with sensorineural hearing loss].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2024Article
- Hypogonadism evaluation: clinical examination is the key.BMJ case reports · 2023Article
- A case of novel mutation in ANOS1 (KAL1) gene and review of Kallmann syndrome.Endocrinology, diabetes & metabolism case reports · 2023Article
- A functional spectrum of PROKR2 mutations identified in isolated hypogonadotropic hypogonadism.Human molecular genetics · 2023Article
- Reproductive Phenotypes and Genotypes in Men With IHH.The Journal of clinical endocrinology and metabolism · 2023Article
- Case Report: Multiple prolactinomas in a young man with Kallmann syndrome and familial hypocalciuric hypercalcemia.Frontiers in endocrinology · 2023Article
- Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders.Frontiers in endocrinology · 2023Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
contextThe complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening.
objectiveThe objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. SUBJECTS: Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes.
main outcome measuresReproductive and nonreproductive phenotypes within each genetic group were measured.
resultsMale KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 ± 0.1 mL vs 3.7 ± 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors.
conclusionsCertain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.