genetic and physical characteristics of rett syndrome

Conditions: Rett Syndrome; MECP2 Duplication Disorder; Rett-related Disorder

Summary: rett syndrome (rtt) is a genetic brain disorder that occurs almost exclusively in females and is usually caused by a change (mutation) in the gene mecp2. the disorder is characterized by multiple developmental problems, as well as behavioral features, such as repetitive stereotypic hand movements, including hand washing, wringing, and tapping. while there is no cure for rtt, recent advances in the understanding of the disease suggest that the development of new, effective therapies is promising. this study will gather information on the genetic defects that cause rtt, the physical expressions of these defects, and disease progression. in turn, this may direct the development of future treatments. expanded studies include individuals with mecp2 duplication disorder, and rtt-related disorders including individuals with mecp2 mutations, but not meeting obligatory criteria for the diagnosis of rtt and individuals with mutations in cdkl5 and foxg1 some of whom meet criteria for atypical rtt.

rtt is a brain disorder that causes problems with childhood development. it is usually caused by an abnormality (mutation) in the gene mecp2. rtt can cause severe impairments in movement and communication skills, including speech and social interaction. the first signs of rtt include loss of acquired speech and loss of purposeful hand use for activities such as eating or playing. individuals may also develop abnormal walking, repetitive hand movements, such as clapping or wringing, and abnormal breathing while awake. effective treatments for rtt are currently lacking. there is also inadequate information about the link between rtt clinical features and its genetic basis. in order to prepare for future clinical trials that may lead to effective therapies, it is important to collect accurate information about the characteristics of rtt and the pattern of disease progression. this study will gather historical and physical examination data to establish phenotype-genotype correlations. data on survival and quality of life in females with rtt and males with mecp2 gene mutations will also be evaluated. mecp2 duplication disorder affects principally males who have one and rarely more than one additional copy of mecp2 as well as a variable number of other duplicated genes. these males have absent spoken language, shuffling gait, epilepsy, and, in some, frequent upper respiratory infections or sinusitis. mother of these males are generally normal due to favorable skewing of x-chromosome inactivation, but in some instances may have neurodevelop-mental delays. effective treatments are lacking. it is critical to develop phenotype-genotype correlations and longitudinal natural history data to assist the conduct of clinical trials. rtt-related disorders feature a variety of involvements either due to mecp2, cdkl5, and foxg1 as well as other potential causes of atypical rtt. phenotype-genotype studies and longitudinal natural history data are essential to the conduct of future clinical trials. participants in this observational study will be recruited from the four sites at which the study is being conducted, as well as through the rare disease clinical research network and the international rett syndrome association (irsa). prior to study entry, potential participants are expected to be tested for a mutation in the mecp2 gene. no treatment will be administered at any time during this study. study visits will occur every 6 months until the child is 6 years old and once a year thereafter. at each study visit, participants will be examined to assess physical characteristics of the disorder, such as motor behavior and disease severity. additionally, participants will complete questionnaires about medical history, contact information, and quality of life. the first visit will last approximately 1.5 hours, and every subsequent visit will last approximately 1 hour.

Eligibility criteria:
inclusion criteria: * meets clinical criteria for classic or variant rtt or tests positive for an mecp2 gene mutation or a mecp2 duplication or a mutation in cdkl5 or foxg1. exclusion criteria: * unwilling or unable to travel to study sites for annual or biannual evaluations

Keywords: loss of purposeful hand use syndrome loss of communication stereotypic hand movements mecp2 mutation mecp2 duplication cdkl5 mutation foxg1 mutation