Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate

Cleft Lip and Palate Clinical Trial

Official title:

The Genetics of Neuroendocrine Reproductive Disorders and of the Cleft Lip and/or Palate

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01601171
• Other study ID #: 345/11
• Status: Recruiting
• Start date: March 2012
• Est. completion date: March 2030

Study information

• Verified date: June 2022
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: Emmanuelle Paccou
• Phone: +41 79 556 60 13
• Email: emmanuelle.paccou[@]chuv.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: March 2030
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Amenorrhea
• Cleft Lip
• Cleft Lip and Palate
• Cleft Palate
• Hypogonadism
• Hypogonadotropic Hypogonadism
• Hypothalamic Amenorrhea
• Kallmann Syndrome
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome
• Precocious Puberty
• Puberty, Precocious
• Syndrome

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne	Vaud

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois	Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

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, — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rare sequence variant(s) in gene(s)	The investigators aim to discover genes associated with reproductive disorders by identifying rare sequence variants (mutations) in patients	1 year (ongoing if no variants are identified)
Secondary	functionality of identified rare sequence variants (mutations)	The investigators will use a variety of scientific approaches to assess the functional impact of the identified rare sequence variants (mutations)	1 year (following variant identification)
Secondary	mode of inheritance	The investigators will examine family pedigrees and study family members to determine the inheritance patterns (how the disorder is transmitted in the family)	1 year (following variant identification)
Secondary	genotype-phenotype correlation	The investigators will study the phenotypic spectrum (how the disorder presents clinically) in patients with identified rare sequence variants (mutations)	1 year (following variant identification)

External Links

•   Web page for the Principal Investigator Nelly Pitteloud's research group