Genetic Study of Congenital Aganglionosis (Hirschsprung Disease) in Down Syndrome
The major goal of this study, which began in 1991 at Case Western University, is to identify the genes involved in Hirschsprung disease (HSCR).
HSCR results as a consequence of the congenital absence of nerve cells (ganglia) in the bowel. The length of the affected (aganglionic) segment of the bowel is variable; in most patients the aganglionic segment is shorter (S-HSCR, 80%) and in others it is longer (L-HSCR, 20%). HSCR most often occurs as an isolated condition, however approximately 30% of affected individuals have associated health concerns or genetic syndromes. It is estimated that 0.6-3% of all individuals with Down syndrome also have Hirschsprung disease, and that 2-10% of all Hirschsprung patients have Down syndrome. It may be that there is a gene on chromosome 21 that contributes to causing the disease, and this is an active area of research. In addition, although HSCR is largely sporadic, there are families in which multiple individuals are affected with HSCR. As a result of all these variable factors, delineating the genetics of HSCR has been challenging. The goal of our research study is to identify the genes involved in HSCR in Down syndrome and to understand this developmental disorder at the genetic level.
Although we have identified the major genes thought to cause HSCR, we are currently investigating how these genes interact and we are searching for additional genes that may contribute to the development of the intestinal nervous system. In particular, we are investigating the association between Down syndrome and Hirschsprung disease. Our previous studies have suggested that the 21q22 region may contain a modifier gene(s) for Hirschsprung disease.

The Institute of Genetic Medicine is seeking volunteers for our research study who have Down syndrome and Hirschsprung disease. Research study volunteers will be asked to:

  1. complete a medical/family history questionnaire,
  2. provide informed consent,
  3. submit blood samples from the individual(s) affected with Hirschsprung disease and his/her parents.
Julie Albertus, MS, the research study coordinator would be happy to speak with you to answer any questions you may have about our research study. If you decide to participate, the questionnaire, consent forms, and blood collection kit will be mailed to you. Please note that any costs associated with having your blood drawn will be reimbursed.
Johns Hopkins Hospital
600 North Wolfe Street
2-121A Jefferson Street Building
Baltimore, MD 21287
Julie Albertus, MS
Genetic Counselor
Research Study Coordinator
(410) 502-7541
Fax: (410) 502-7544
Aravinda Chakravarti, Ph.D.
Henry J. Knott Professor and Director

Revised: August 6, 2006.