Need for a new international rare disease database: the MECP2 duplication syndrome

Abstract

Background: Individuals who have two or more copies of the MECP2 gene, located at Xq28, have been found to share clinical features and a distinct facial phenotype known as MECP2 duplication syndrome (MDS). The aims of this study are to provide a preliminary snapshot of MDS to inform the development of a new international database. Methods: The International Rett Syndrome Database, first established in 2002, collects data on Rett syndrome and Rett-related disorders including MDS. Results: Data are available on 57 cases (49 males and 8 females) with MDS. Median age at ascertainment was 7.9 years (range 1.2–37.6 years) and at diagnosis 3 years (range 3–37 years). Only 10% had an initial diagnosis of MDS. Less than a third (30%) learned to walk (median age 30 months), while 70% learned to use babble or words (median age 15 months). Speech deterioration was reported in 37%, and only 20% were able to use word approximations or better at ascertainment. The majority (85%) had been hospitalized in the first 2 years of life often because of respiratory infections. Just under half (45%) had seizures, occurring daily in half (56%) of this group. Scoliosis affected a quarter of those aged over 7 years. The majority (90%) had gastrointestinal problems, and a third had a gastrostomy. Respiratory infections and sleep apnoea were common. Conclusion: Parents and clinicians alike need to know more about this disorder, particularly the occurrence of co-morbidities and their management. These data supported by consumer consultation will inform the development of a new MDS-specific international database.