Triple X Syndrome and GRIN2A Mutation in the Clinic for Pediatric Neurology: Clinical and EEG Features

Background/Purpose: Triple X syndrome (karyotype 47, XXX) belongs to the poly X syndromes and occurs in girls with a frequency of 1:1,000. Patients often develop late in motor, language, and psychological terms. Sometimes complex partial seizures can occur with a predominance of epileptic activity in the posterior regions. GRIN2A mutations play a special role in epilepsy in combination with a disorder of language development (spectrum of epilepsy aphasia): CSWS, Landau-Kleffner syndrome, atypical Rolandic epilepsy, etc., with a focus of epileptic activity in most cases centrotemporal. In patients on the epilepsy aphasia spectrum, GRIN2A mutations were found in up to 20% of those affected. Mutations in the GRIN2A gene follow an autosomal dominant inheritance. There are no statistical data in the medical literature on the combination and association between triple X syndrome and GRIN2A mutation.

Methods: We present the case of a 7-year-old child who is affected by the combination of the two diseases (clinical, neurological examinations, video EEG, EEG amplitude mapping, EEG frequency mapping). Triple X syndrome was diagnosed before birth by chorionic villus biopsy. Genetic counseling has taken place. Mother has gestational diabetes. Spontaneous delivery in the 39th week of pregnancy. No postnatal abnormalities.

Results: Currently marked developmental delay with a severe muscular hypotonia of the trunk. Severe restriction in almost all areas (language and communication, mobility, self-care). Microcephaly. Pediatric orthopedic control. Focal epilepsy. Anticonvulsants (valproic acid). Currently without seizures. In the slowed pathological EEG during wakefulness in the delta–theta frequency range, sharp waves appear occipital on the left. No centrotemporal spikes were seen. Last EEG was performed without epileptic activity. There is no visual blocking reaction. Severe general changes.

Conclusion: In this case, there is an extremely rare combination of triple X syndrome and GRIN2A mutation in one and the same child. The diagnosis of specific syndrome in the Clinic of Pediatric Neurology is important for treatment and prognosis.

Publication History

Article published online:
28 October 2021