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

Vaud University Hospital Center

Status: Enrolling

Conditions: Precocious Puberty; Cleft Lip; Cleft Palate; Kallmann Syndrome; Cleft Lip and Palate; Hypogonadotropic Hypogonadism; Polycystic Ovarian Syndrome; Hypothalamic Amenorrhea

Study type: Observational

Funder types: Other

Identifiers

NCT01601171

345/11

Details and patient eligibility

About

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

Full 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

Enrollment: 2,000 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

2,000 participants in 2 patient groups

Patients

Description:

Patients with reproductive disorders with or without cleft lip/palate will be recruited for: * completion of medical questionnaire and review of medical records * family tree (including questions on reproductive disorders and cleft lip/palate) * specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy * smell testing * hearing test * bone density * brain MRI * kidney, testicular/ovarian ultrasound

Family members

Description:

Family members of Patients will be recruited for: * completion of medical questionnaire * specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy * smell testing