Atypical Rett Syndrome: Differential Diagnosis in Pediatric Patients with “Autistic-like” Features

Abstract

Introdution: Rett syndrome (RTT) is a neurodevelopment
disturbance caused by mutations in the MECP2 gene, affecting
mostly female patients. The patients can be distributed in two main
subgroups; classic RTT form, in which the progression presents
characteristic and expected symptoms, and variant (or atypical)
RTT form, evolving with unexpected symptoms. This report is a
comparative study of two atypical RTT cases. Case report: Patient
#1: Female, 17 years old, presented with seizures, hypotonia,
and hypoactivity at the age of 7 years. It was reported a lack of
responsiveness to stimuli until 7 months old. Even after this age, the
hypotonia was notable in comparison to her neurodevelopment,
contributing to a delay in the investigation of a pathogenic
mutation in the MECP2 gene. Patient #2: Female, 7 years old, with
neuropsychomotor delay and autistic characteristics. Brain MRI,
karyotype, SNP-array, and innate errors of metabolism evaluations
were unremarkable. Due to the non-elucidation of the clinical
condition, whole-exome sequencing was performed, and the MEC2
gene mutation was detected. Discussion: RTT is characterized by
motor and communication skills regression in patients with normal
neurological development in the first few months of living, affecting
patients 6 to 18 months old, alongside possible hypotonia, seizures,
and autistic spectrum elements. Even though both patients are
considered as RTT atypical forms, the clinical condition of the first
case is more severe since early childhood, with congenital hypotonia
and neurodevelopment delay, while the clinical condition of the
second patient is milder, with less intellectual and communication
compromising and neuro psychomotor regression.