Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00494169
Recruitment Status : Recruiting
First Posted : June 29, 2007
Last Update Posted : September 1, 2017
Information provided by (Responsible Party):
William F. Crowley, Jr., M.D., Harvard University

Brief Summary:
The aims of this study are: 1) to identify genes that play a role in human pubertal development and reproduction, 2) to characterize the phenotypic spectrum of patients with these gene defects, and 3) to discern the mode of inheritance for disorders caused by these gene defects. We are specifically interested in genes that cause Kallmann syndrome, idiopathic hypogonadotropic hypogonadism (IHH), precocious (early) puberty, and delayed puberty. Individuals do not have to travel to Boston to participate in this study.

Condition or disease
Hypogonadism Kallmann Syndrome Puberty, Delayed Puberty, Precocious Hypothalamic Amenorrhea Anosmia GnRH Deficiency

Detailed Description:


Our work is divided into two main areas of investigation:

  1. the discovery of new, yet-undiscovered genes for conditions of early (i.e. precocious) puberty, delayed puberty, absence of pubertal development (i.e. Kallmann syndrome) as well as normal puberty that is accompanied by an altered reproductive system later in life (i.e. hypothalamic amenorrhea in women or very low testosterone levels in men). Identification of new genes requires either a single large family or a collection of smaller families.
  2. a detailed examination of the genes already implicated in causing these conditions.

There are several other important aspects about our program:

  • This analysis will detect DNA abnormalities only in those DNA segments being screened. The turnaround time to process a sample is approximately 6-9 months. We must receive a signed consent form in order to begin analysis on a blood sample.
  • Our laboratory is located in Massachusetts General Hospital, Boston MA and is largely funded by the National Institutes of Health. We are a research laboratory and not a CLIA certified clinical laboratory.
  • Even if a patient is the only member of his/her family affected by one of the conditions mentioned above, obtaining blood samples on other family members, including parents and siblings is often important to our work.
  • It is every individual's responsibility to notify the research team he/she would like to obtain research results. The patient must sign a second consent form before receiving such information.

Study Procedures and Risks

  • You will be asked to give approximately 3-5 tablespoons of blood for this research project. There is a risk of bruising and a very small amount of bleeding associated with blood drawing.
  • You will be asked to fill out a medical history checklist, indicating the presence or absence of clinical features that may be associated with abnormalities in pubertal development.
  • Since absence of puberty is sometimes associated with limited or no smell ability, you may be asked to try to identify the odors in a scratch and sniff test. This will take about 15 minutes.
  • Your family history can give us clues to determine how your condition was inherited. Therefore, a detailed family history, at least back to your grandparents will be obtained by a researcher.


There are no direct benefits to you from participation in this study. Some genes for this condition are known, other genes have yet to be discovered. If this study discovers what genes are responsible, it will help to further the understanding of this disorder. It is possible that the genetic cause of your reproductive disorder may be learned. This information can be shared with you at your request.

When contacting us, please include in your message a description of your diagnosis, your pubertal history (age when you hit pubertal hallmarks, e.g., growth spurt; body hair; voice deepening and genital growth for men; menstruation and breast development for women) and your reproductive history.

Study Type : Observational
Estimated Enrollment : 5000 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Molecular Basis of Inherited Reproductive Disorders
Study Start Date : January 1999
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Identification of DNA abnormalities [ Time Frame: 5/2015 ]

Biospecimen Retention:   Samples With DNA
WBC are transformed into immortalized cell lines.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects who

  1. fail to go through a normal, age-appropriate, spontaneous puberty, and abnormal hormone levels.
  2. have abnormally early development of puberty (Precocious Puberty) OR
  3. display low gonadotropins in adulthood after having gone through normal pubertal development.

Family members of these patients.


Inclusion Criteria:

  • Failure to go through a normal, age-appropriate, spontaneous puberty, and abnormal hormone levels.
  • Children with abnormally early development of puberty (Precocious Puberty)
  • Adults who display low gonadotropins in adulthood after having gone through normal pubertal development.
  • Family members of these patients.

Exclusion Criteria:

  • pituitary tumor
  • high prolactin levels

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00494169

Contact: Ravi Balasubramanian, MD, PhD 617-726-8432
Contact: Kathryn Salnikov, BS 617-726-1309

United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kathryn Salnikov, BS    617-726-1309   
Contact: Ravi Balasubramanian, MD, PhD    617-726-8432   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: William F Crowley, Jr., MD Massachusetts General Hospital

Additional Information:
Publications of Results:

Other Publications:
Kallmann FJ, Schoenfeld WA. The genetic aspects of primary eunuchoidism. American Journal of Mental Deficiency 158:203-236, 1944.

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: William F. Crowley, Jr., M.D., Professor, Harvard University Identifier: NCT00494169     History of Changes
Other Study ID Numbers: U54HD028138 ( U.S. NIH Grant/Contract )
First Posted: June 29, 2007    Key Record Dates
Last Update Posted: September 1, 2017
Last Verified: August 2017

Keywords provided by William F. Crowley, Jr., M.D., Harvard University:
Idiopathic Hypogonadotropic Hypogonadism
Kallmann Syndrome
Pituitary Abnormalities
GnRH deficiency

Additional relevant MeSH terms:
Kallmann Syndrome
Olfaction Disorders
Puberty, Precocious
Puberty, Delayed
Pathologic Processes
Gonadal Disorders
Endocrine System Diseases
Menstruation Disturbances
46, XY Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms