Cleft Lip, Cleft Lip and Palate, Cleft Palate, Hypogonadotropic Hypogonadism, Hypothalamic Amenorrhea, Kallmann Syndrome, Polycystic Ovarian Syndrome, Precocious Puberty
Conditions
Keywords
GnRH deficiency, hypogonadism, anosmia, infertility, cleft lip, cleft palate, cryptorchidism, microphallus
Brief summary
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
Interventions
None listed
Sponsors
Swiss National Science Foundation
Centre Hospitalier Universitaire Vaudois
Study design
Observational model
CASE_CONTROL
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| rare sequence variant(s) in gene(s) | 1 year (ongoing if no variants are identified) | The investigators aim to discover genes associated with reproductive disorders by identifying rare sequence variants (mutations) in patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| functionality of identified rare sequence variants (mutations) | 1 year (following variant identification) | The investigators will use a variety of scientific approaches to assess the functional impact of the identified rare sequence variants (mutations) |
| mode of inheritance | 1 year (following variant identification) | The investigators will examine family pedigrees and study family members to determine the inheritance patterns (how the disorder is transmitted in the family) |
| genotype-phenotype correlation | 1 year (following variant identification) | The investigators will study the phenotypic spectrum (how the disorder presents clinically) in patients with identified rare sequence variants (mutations) |
Countries
Switzerland
Contacts
Primary ContactEmmanuelle Paccou
Backup ContactMichela Adamo, MD
Outcome results
None listed