ABSTRACT
Christianson syndrome is a rare X-linked disease caused by mutations in the SLC9A6 gene. The clinical manifestations are male developmental delay, language disorder, seizures, mental retardation, ataxia, microcephaly and so on. Two cases of male children with Christianson syndrome were reported. The proband was 1 year and 11 months old. Clinical manifestations include microcephaly, global developmental delay, and seizures. The electroencephalogram showed that the central midline region of spikes and slow waves were emitted, and all exons sequencing detected a mutation in the SLC9A6 gene chrX: 135084373 [c.803+1(IVS6)G>A]. The proband′s brother was 4 years and 8 months old. The clinical manifestations were similar. The electroencephalogram showed spikes and spines in the Rolandic area on both sides. Slow waves and spiny slow waves were emitted. Magnetic resonance imaging suggested brain atrophy. The genetic verification results were consistent with the proband. The SLC9A6 gene c.803+1(IVS6) G>A splicing mutation was a pathogenic mutation in this family.
ABSTRACT
Objective:To retrospectively analyze the clinical data of Christianson syndrome caused by SLC9A6 gene mutation and related literatures.Methods:The clinical data of one Christianson syndrome patient caused by SLC9A6 gene variation in Children′s Hospital of Zhengzhou University were collected, meanwhile the relevant literature was reviewed. The examination of video electroencephalogram, auditory brainstem response, and cranial magnetic resonance imaging (MRI) was performed. Whole exon sequencing and mitochondrial gene detection were performed for 3 persons in the family, and the suspected mutation sites were verified by Sanger sequencing.Results:A boy, 7 years old, presented with epilepsy, language retardation and mental retardation. Now he can only say overlapping words, execute simple instructions, denying family history of genetic disease and genetic metabolic disease. The patient′s uncle had the history of febrile convulsions in childhood. At present, speech and intelligence are impaired, and the left limb movement is slightly limited. The patient′s mother was mildly retarded, without epilepsy. The video- electroencephalogram of the patient was shown below (April 2021): abnormal electroencephalogram; background activity was slightly slow; the bilateral frontotemporal region was dominated by multi-focal spiky wave, spiky slow wave and slow wave in each waking and sleeping stage, which can be generalized and extensive; in the sleeping stage, the discharge index in non-rapid eye movement stage was about 75%. The auditory brainstem response was shown below (October 2021): the left 70 dB Ⅰwave latency was prolonged; the Ⅰwave Ⅴ wave shape was poor; the threshold was 20 dB (the high frequency threshold was normal); the right 70 dB Ⅰwave latency was prolonged; the wave form was poor; the amplitude was lower than that of the contralateral side; Ⅲ wave Ⅴ wave shape was poor; the threshold was 30 dB (the high frequency threshold slightly increased). Brain MRI thin-section scan was shown below (January 2021): subarachnoid space of bilateral temporal poles widened, and no obvious abnormal signal was found in brain parenchyma; sinusitis. Whole exome sequencing of 3 persons in the family indicated that the proband had a hemizygous variant c.616C>T (p.R206 *) in the SLC9A6 gene. Using the SLC9A6 gene and Christianson syndrome as the key words, 94 foreign literatures from January 1989 to January 2022 were researched. Totally, 81 Christianson syndrome patients caused by SLC9A6 gene mutation were reported. The age of onset ranged from neonatal period to adulthood, and the clinical manifestations were heterogeneous. The symptoms of male patients mainly included epilepsy, severe cognitive impairment, ataxia, cerebellar atrophy, and psychomotor retardation. Conclusions:The hemizygous variant of SLC9A6 gene (c.616C>T) is the etiology of this patient. The possibility of Christianson syndrome shall be considered for recurrent epilepsy with poor efficacy of antiepileptic drugs, status epilepticus during slow-wave sleep, and delayed development of motor intelligence. Genetic testing is helpful for definite diagnosis and treatment.