DUPLICATION OF MECP2 IN A GIRL WITH RETT SYNDROME VARIANT

Objectives: To report a duplication of the MECP2 gene as a possible cause of forme fruste Rett syndrome (RTT) variant.

Methods: The proband was examined, and medical and family histories were obtained. Brain MRI, as well as genetic studies including karyotype, subtelomere FISH, FISH for deletion 22q11, and screening for fragile X and Rett syndrome, were performed.

Results: A 13 year-old girl presented with mild mental retardation. She was the only child of consanguineous parents and was born after a normal pregnancy and delivery. Early developmental milestones were normal. She attended a regular kindergarten, but was transferred to special education at age 5.5 years. Now, at age 13, she is well oriented and has normal speech. Gait, balance, coordination and deep tendon reflexes are normal. She has occasional hand-washing movements and a discrete tremor of both hands. Full Scale IQ score was 63. MRI of the brain was normal. Analysis of the MECP2 region by MLPA techniques showed a duplication of the MECP2 gene. X-inactivation studies in the proband and her mother are in progress. Conclusion: The finding of a duplication of MECP2 in a girl with forme fruste RTT could possibly expand the phenotypic spectrum of MECP2 duplications and underlines the importance of quantitative analysis of MECP2 in patients with variant RTT without point mutations. To date, duplications of MECP2 have been reported in 2 girls, one with classical RTT and complete skewing of X-inactivation (XCI), and one with preserved speech variant RTT. MECP2 duplications have also been reported in males with severe mental retardation and progressive neurological symptoms in 6 families and 2 sporadic patients. All affected female carriers in the families that were tested, showed extreme or complete XCI.