The Clinical Predictors That Facilitate a Clinician's Decision to Order Genetic Testing for Rett Syndrome

Abstract

Background: Rett syndrome is a common genetic cause of intellectual disability in girls caused by a mutation in the MECP2 gene. Diagnosis is based on clinical criteria. The aim was to compare the frequencies of the clinical criteria in patients with and without MECP2 mutations.

Methods: We performed a retrospective review at a children's hospital of patients who underwent MECP2 testing from 2008 to 2013. Logistic regression was performed to determine which criteria were most predictive of MECP2 status.

Results: Of 169 patients who met inclusion criteria, 46 (27.2%) were MECP2 positive. Loss of language skills (MECP2+ 100% versus MECP2- 87.8%; P = 0.012) was the most common finding among both groups. Other main criteria were more common in MECP2 patients: gait abnormalities (84.8% versus 27.6%; P < 0.0001); stereotypic hand movements (76.1% versus 15.5%; P < 0.0001); loss of hand skills (71.7% versus 4.9%; P < 0.0001). Logistic regression analysis including all four criteria demonstrated language loss was not predictive.

Conclusions: Loss of hand skills resulted in the highest odds of having a positive genetic test. Gait abnormalities and stereotypic hand movements were also strong predictors of MECP2+ testing. Many individuals with language delay had genetic testing; however, this is the least specific of the major criteria. These findings have implications for which patients should have genetic testing.

Keywords: MECP2 gene test; Rett syndrome; cognitive/behavioral disorders; genetic testing for Rett; stereotypic hand movements.