Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Kallmann Syndrome, Hypogonadotropic Hypogonadism, Hypothalamic Amenorrhea, Polycystic Ovarian Syndrome. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Switzerland
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
The Genetics of Neuroendocrine Reproductive Disorders and of the Cleft Lip and/or Palate
Overview
The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate.
Detailed description
The World Health Organization estimates approximately 10% of couples experience some sort of infertility problem.
In humans, puberty is the process through which we develop reproductive capacity.
The timing of puberty varies greatly in the general population and is influenced by both genetic and environmental factors. In extreme cases of pubertal delay, puberty progresses only partially or not at all and results in the clinical picture of congenital hypogonadotropic hypogonadism (CHH), either accompanied by anosmia in 50% of cases (Kallmann syndrome \[KS\]) or by normal sense of smell (nCHH), with a male: female ratio of 4:1.
CHH is due to GnRH deficiency (incidence 1: 4,000-10,000) and result in the failure of sexual maturation and infertility. It is genetically heterogeneous, with multiple patterns of inheritance and several associated loci. In the clinical spectrum of GnRH deficiency, CHH may also be associated with a cleft lip/palate (CL/P) in 5 to 7% of cases. However, this prevalence increases up to 40% in CHH patients carrying a mutation in a CL/P gene, suggesting a genetic overlap between CHH and CL/P.
Disorders of puberty have provided insight into the biology of reproduction and genetic technologies have enabled us to deepen understanding in this field. The focus of this study is to better understand the genetic control of puberty and human reproduction as well as its link with CL/P.
Increasing understanding of the molecular basis (genes) of inherited reproductive disorders and CL/P may enable investigators to:
* improve diagnostic testing and treatments for these problems * develop new diagnostic tests and therapies for patients * enhance counseling for patients and families with reproductive disorders * enhance counseling for patients and families with cleft lip/palate
Primary outcome measures
- rare sequence variant(s) in gene(s) [Time frame: 1 year (ongoing if no variants are identified)]
Secondary outcome measures (3)
- functionality of identified rare sequence variants (mutations) [Time frame: 1 year (following variant identification)]
- mode of inheritance [Time frame: 1 year (following variant identification)]
- genotype-phenotype correlation [Time frame: 1 year (following variant identification)]
Eligibility criteria
Inclusion Criteria:(any of the following conditions)
- hypogonadotropic hypogonadism
- Kallmann syndrome
- adult-onset hypogonadotropic hypogonadism
- hypothalamic amenorrhea
- polycystic ovarian syndrome
- primary gonadal failure
- precocious puberty
- cleft lip/palate
- family members of the above groups
Exclusion criteria
- acute illness/hospitalization
- pituitary tumors
- iron overload (hemochromatosis)
- infiltrative diseases (sarcoidosis)
- chronic alcohol abuse
- illicit drug use
- anabolic steroid abuse
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Case-control
Study locations
Switzerland · 1 center
- Centre Hospitalier Universitaire Vaudois (CHUV) — Lausanne
Publications
- Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individu PMID 23643382
- Villanueva C, Jacobson-Dickman E, Xu C, Manouvrier S, Dwyer AA, Sykiotis GP, Beenken A, Liu Y, Tommiska J, Hu Y, Tiosano D, Gerard M, Leger J, Drouin-Garraud V, Lefebvre H, Polak M, Carel JC, Phan-Hug F, Hauschild M, Plummer L, Rey JP, Raivio T, Bouloux P, Sidis Y, Mohammadi M, de Roux N, Pitteloud N. Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity wit PMID 25394172
Identifiers
NCT: NCT01601171 · 345/11