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

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.

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.

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.

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.