AUTISM SPECTRUM DISORDERS RESEARCH

Behavioral Phenotype of Children with Cornelia
de Lange Syndrome (CdLS)

Principal Investigator: Marco Grados, M.D., M.P.H.

This research project, funded by the CdLS foundation of the USA, aims to delineate the behavioral phenotype of CdLS in children ages 5-17 years in relation to measure of maladaptive behavior, autism features, compulsive behaviors, medical manifestations of the disorder, parental stress and family functioning. The design uses mail questionnaires and phone interviews to characterize the full behavioral phenotype of CdLS to eventually associate any behavioral patterns obtained to genetic testing. The CdLS gene, NIPBL, was discovered in 2005 and is a regulator gene of homeobox and other gene systems. While the relationship of NIPBL to behavioral manifestations in CdLS is probably complex, the known genetic networks that NIPBL may impact can give some clues to what causes maladaptive behaviors in children with CdLS. For example, limb sculpting changes (2,3 toe syndactyly) has been found to be highly associated with autistic features in the pilot data, which point to gene networks in common between the two phenomena. 

The Frequency of Smith-Lemli-Opitz Syndrome and
Hypocholesterolemia in a Population with Autism

Principal Investigator: Elaine Tierney, M.D.  
Co-investigator: Geeta Sarphare, Ph.D.             

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a deficiency in the last step in cholesterol biosynthesis. Besides causing physical abnormalities, the deficiency affects the synthesis and metabolism of sterol-derived compounds, and the proper functioning of serotonin and other brain receptors. This study will asses for SLOS and quantify cholesterol and all sterol precursors of cholesterol in the blood samples from individuals (age 2 years through adulthood) who gave samples of blood to the Autism Genetics Resource Exchange.

Publications:             

Tierney E, Bukelis I, Thompson RE, Ahmed K, Aneja A, Kratz L, Kelley RI. Abnormalities of Cholesterol Metabolism in Autism Spectrum Disorders, American Journal of Medical Genetic, Part B: Neuropsychiatric Genetics. 2006; 141B:666-668.

The Behavioral Phenotype of Smith-Lemli-Opitz Syndrome  

Principal Investigator: Elaine Tierney, M.D.  
Co-investigator: Geeta Sarphare, Ph.D.             

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a deficiency in the last step in cholesterol biosynthesis. Besides causing physical abnormalities, the deficiency affects the synthesis and metabolism of sterol-derived compounds, and the proper functioning of serotonin and other brain receptors. The aim is to characterize the behavioral phenotype and quantify the degree of symptoms of autism in SLOS. Individuals with SLOS from age 6 months and older are interviewed and forms describing the person's behavior are completed.

Publications:      

Tierney E, Nwokoro N, Porter FD, Freund S, Ghuman JK, Kelly RI. The behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome. American Journal of Medical Genetics, 2001 Jan; 98:191-200.

Investigation of Simvastatin Therapy in Smith-Lemli-Opitz Syndrome

Principal Investigator: Elaine Tierney, M.D. 
Co-investigator: Alka Aneja          

The purpose of this study is to see if simvastatin is helpful and safe to use in youth 4-18 years old with Smith-Lemli-Opitz Syndrome (SLOS). We also want to see if it will help with behavior and the cholesterol balance in the body. Over 26 months, participants will visit the Kenneday Kreiger Institute and National Institutte of Health (NIH) five times at each site. This study is being done in partnership with a study at the NIH in Bethesda, Maryland (Dr. Porter). At Kennedy Krieger Institute, the individuals will have speech and language testing, as well as intelligence testing three times. They have other behavioral testing and an EEG five times during the study. They will be on the study medicine for 1 year and simvastatin for 1 year.