Early Infantile Ataxia As Cardinal Symptom for an X-Linked MECP2 Mutation

Case Report: This case study reports about two brothers who initially showed a tremor as well as a slowly progressive ataxia since infancy. Parents were healthy, not consanguineous. There are no neurological diseases in the family history. Pregnancy was without complications and normal early childhood development. They started walking at 12 months and developed speech like other children their age. The ability to ride a bike was gained at the age of 3 years. In their second year, both the children started to develop a fine intention tremor as well as dysmetria with increasing limitation of fine motor skills plus a cerebellar ataxia. Shortly after, nocturnal tonic-clonic seizures started to happen. During infancy, one could notice mild developmental deficits combined with autistic features. They initially started at a regular primary school but despite the support they were getting they had to change to a special-needs school after 3 years. On top of the slowly progressive ataxic disorder, the children are increasingly restricted by cognitive, social, and emotional competence deficits as well as aggressive impulsive outbreaks in everyday life.

Methods and Results: Electroencephalography (EEG): multiregional epilepsy-typical potentials (ETP), activation during sleep, EEG seizure pattern bilateral frontal, frequent nocturnal short clonic seizures, nerve conduction velocity (NCV), somatosensory evoked potentials (SEP), visual evoked potentials (VEP), fundoscopy without pathological findings. Cerebral magnetic resonance imaging (MRI) of the elder brother was done for four times and never yielded pathological findings. Extensive metabolic diagnosis was unremarkable. Array comparative genomic hybridization without pathological findings was observed. Examination of the mother: no shift of X-inactivation in the range of androgen receptor was seen. Negative mutation analysis for hereditary spinocerebellar ataxia and for ataxia with oculomotor apraxia type 2 (AOA2) was also observed. At the epilepsy-panel-diagnostics of both the children, we could detect a mutation in the MECP2 gene variant c.419C>T;p.A140V (hemizygous).

Conclusion: Mutations in the MECP2 gene cause the X-linked dominant Rett syndrome in female patients. MECP2 mutations can also cause mental retardation of boys. The degree of severity depends on the localization of the mutation in the gene. Some boys also show a typical course of the disease (start of the regressive development between 6 and 18 months) and the characteristic stereotypy of the Rett syndrome (the hand washing movement). In those cases, the mutations occur in form of somatic mosaics. The cardinal symptoms of our case were the combination of cerebral ataxia and the early development of epilepsy during an otherwise normal psychomotoric and mental development of the infants. In this respect, MECP2 mutations should soon be considered in differential diagnosis when ataxia occurs during infancy.