Lewis Holmes, MD

Genetics

Summary of Research

The Active Malformations Surveillance Program has been conducted since 1972 to identify all infants born with major malformations at Brigham and Women’s Hospital. The project is now supported by a subcontract from the Massachusetts Department of Public Health (MDPH) to MGH. In this study the frequencies of many major malformations have been determined. Attention has been given to the many genetic and non-genetic causes of abnormalities, such as congenital diaphragmatic hernia and renal agenesis. This project is part of the National Birth Defects Prevention Study, an eight-state consortium coordinated by the Birth Defects Center at the Centers for Disease Control in Atlanta. Contact information: Marie-Noel Westgate, Study Coordinator; Tel: 617-732-4268, Fax: 617-264-6803.

The North American AED (antiepileptic drug) Pregnancy Registry was established at MGHfC in 1997. Pregnant women taking antiepileptic drugs for any medical reason are enrolled by telephone and interviewed three times. The goal is to determine the frequency of major malformations in her infant who had been exposed to one of the many different anticonvulsant drugs. The Registry has published significant findings for exposure to three different drugs as monotherapy: phenobarbital, valproate and lamotrigine. All findings for all drugs will be published in 2007 and 2008.The website is: www.aedpregnancyregistry.org Contact information: Caitlin R. Smith, Marketing Director; Tel: 617-726-3179, Fax: 617-724-1911

The Anticonvulsant Follow-up Study has been underway since 1990. Children ages 4 to 16 have been evaluated to determine whether or not exposure during pregnancy to an anticonvulsant drug has caused deficits in IQ and any physical abnormalities. The drugs studies have included phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital, lamotrigine and valproate. The developmental psychologist who has supervised and carried out the intelligence testing is Jane Adams, Ph.D., Professor of Psychology at the University of Massachusetts, Boston. Dr. Leslie Will, an orthodontist at the Harvard Medical School of Dental Medicine, and Dr. Brent Coull, a biostatistician at the Harvard School of Public Health, are major collaborators.Contact information: Uma Deshmukh, Coordinator; Tel: 617-724-1252, Fax: 617-724-1911

The Follow-Up Study for the North American AED Pregnancy Registry began in 2005, to evaluate the long-term effects of the use of antiepileptic drugs during pregnancy, with a specific focus on carbamazepine, lamotrigine, and valproate.  The goal of the study is to determine what impacts, if any, these three medications have on the cognitive, social, and psychological development of the exposed child, and to compare the rates of developmental delays and the prevalence of autism among these groups.  Jane Adams, Ph.D., Professor of Psychology at the University of Massachusetts, Boston, serves as a co-investigator of this study.  Contact information: Uma Deshmukh, Study Coordinator, Tel: 617-724-1252, Fax: 617-724-1911.

The Limb Deficiency Research Study began in 2007, to investigate genetic and environmental risk factors in pregnancy associated with the development of Amniotic Band Limb Deformity and Terminal Transverse Limb Deficiency with Nubbins.  Adults and parents of children affected with one of these limb differences are invited to participate in the study, which involves two telephone questionnaires, medical record review, and a routine physical examination of the affected limb(s) for those that live locally.  Contact information: Uma Deshmukh, Study Coordinator, Tel: 617-724-1252, Fax: 617-724-1911.

The Valproate Follow-Up Study has been underway since 2004.  This study is investigating gene*-environment interactions in a population exposed to Valproate (brand name Depakote), an anticonvulsant drug that has been associated with increased risk of Autism or Autism Spectrum Disorders (ASDs) in exposed children.  Adults and children over age 2, who were exposed to Valproate during pregnancy, are currently being evaluated for symptoms of ASDs, as well as for genetic susceptibility based on the presence of candidate genes for autism.  The study is being conducted in collaboration with Dr. Margaret Bauman, Director of the LADDERS (Learning and Developmental Disabilities Evaluation and Rehabilitation Services) program at MGH, and researchers at the University of Rochester Medical Center, in Rochester, NY.  Contact information: Uma Deshmukh, Study Coordinator, Tel: 617-724-1252, Fax: 617-724-1911.

Contact information

Phone: 617-726-1742
Fax: 617-724-1911

Prenatal Diagnosis Center

*All living things are made of cells.  Genes are the parts of cells that contain the instructions which tell our bodies how to grow and work, and determine characteristics such as hair and eye color.  Genes are inherited (that is, passed from parent to child).