HomeResearchIntramural ResearchResearch Branches at NHGRIMedical Genetics Branch Muenke Lab

Maximilian Muenke, M.D. Chief & Senior Investigator Medical Genetics Branch Head Human Development Section Director Medical Genetics Residency and Fellowship Training Programs Director Combined Pediatrics and Medical Genetics Residency Training Program Abitur, Goethe-Gymnasium, Germany, 1972 M.D. Free University of Berlin School of Medicine, 1979 (301) 402-8167 (301) 480-7876 muenke@nih.gov Building 35, Room 1B203 35 Convent Dr, MSC 9999 Bethesda, MD 20892-9999 Selected Publications Third NIH Conference on Holoprosencephaly, 2004 Second NIH Conference on Holoprosencephaly and Early Embryonic Development, 2002 First NIH Conference on Holoprosencephaly, 2001

Dr. Muenke's research program seeks to improve knowledge about the formation of the central nervous system and to elucidate the origin of developmental disabilities and mental retardation. Specifically, his laboratory investigates birth defects that affect normal embryonic development and lead to neurological impairment. His two major areas of focus are holoprosencephaly and attention deficit hyperactivity disorder.

Holoprosencephaly (HPE) is a common brain birth defect that occurs in one in 250 embryos. HPE is characterized by the failure of the embryonic brain to divide properly into left and right hemispheres during early development. It frequently results in fetal demise, so the live birth rate is not as high: approximately one in 10,000. Children born with the disorder show various degrees of developmental disabilities and mental retardation.

Dr. Muenke's laboratory discovered several genes associated with HPE and, in doing so, illuminated many of the molecular processes involved in early embryonic development. The first human HPE-related gene his group identified was Sonic Hedgehog (SHH), a gene initially found in fruit flies and named for the prickly appearance it gives them. Dr. Muenke and other investigators have since identified a number of additional genes in the Sonic Hedgehog and Nodal signaling pathways that are implicated in HPE. However, these genes still account for only 20 percent of documented HPE cases. Dr. Muenke's laboratory, thus, continues its hunt for new HPE-associated genes.

Dr. Muenke's group also is studying environmental factors that may affect the development of HPE, particularly cholesterol. It is well-known that cholesterol is necessary for the activation of SHH, and, in animal models, researchers have found an association between low maternal cholesterol during pregnancy and birth defects in their offspring. There have been reports of babies with various birth defects, including HPE, being born to women who took cholesterol lowering statin drugs during pregnancy. One of Dr. Muenke's goals is to conduct a larger study to determine whether low maternal cholesterol can indeed adversely affect embryonic development. In related research, Dr. Muenke is studying laterality defects, or abnormal left-right positioning of body organs. In vertebrates, laterality defects occur very early in developmental processes, allowing some organs to end up on the wrong side of the body. Many people are unaware that they are affected by these disorders, but severe symptoms can (and often do) arise in their children.

Another major research area for Dr. Muenke's group involves understanding the genetic basis of attention deficit/hyperactivity disorder (ADHD). ADHD is the most common behavioral disorder in children; it affects at least four percent to six percent of school-age children and five times as many boys as girls. ADHD, which is characterized by impulsiveness, hyperactivity, and attention problems, has been recognized as a distinct disorder for many years. Its cause has remained a mystery, although environmental factors were considered the most likely culprits. Over the past decade, however, studies of twins, adopted children, and families with a high prevalence of ADHD have shown that genetic factors, rather than environmental factors, are the major underlying cause of ADHD.

Building on research by investigators in Colombia, South America, studying 18 large, multigenerational families with a high incidence of ADHD, Dr. Muenke's laboratory conducted detailed phenotyping and genotyping of this population. His group found strong evidence for familial ADHD, including comorbidity to other behavioral disorders, such as nicotine dependence. Dr. Muenke's laboratory has now identified several candidate regions for ADHD in this population and is fine-mapping these regions to help identify specific contributing genes. They are conducting a similar study of more than 1,000 families in the United States. Because of the typically smaller size of American families, this second arm of the study focuses on families with only two children, at least one of whom has ADHD.

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Last Reviewed: June 16, 2008