Global developmental delay and epileptic encephalopathy caused by SPTAN1 gene mutations in 3 cases and literature review / 中华神经科杂志

ABSTRACT

Objective:To summarize the clinical manifestations, gene variations,and treatment of cases with SPTAN1 gene variations characterized by global developmental delay or epileptic encephalopathy. Methods:Three patients with SPTAN1 gene mutations which caused developmental epileptic encephalopathy type 5 admitted to the Department of Pediatrics, Xiangya Hospital, Central South University from August 2019 to September 2021 were collected. The studies till December 2021 were searched with keywords of " SPTAN1" and "developmental and epileptic encephalopathy 5" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical manifestations, genetic variations, treatments and prognosis of patients with SPTAN1 gene variations were summarized. Results:All 3 patients presented with global developmental delay, infant onset. Patient 1 showed early-onset epileptic encephalopathies and microcephaly. Patient 2 had an atrial septal defect. Cranial magnetic resonance imaging (MRI) of patient 3 showed cerebellar hypoplasia.Antiepileptic seizure therapy was partially effective, but failed to control the spasm. Development was slightly improved after rehabilitation training and other treatments, but still lagged behind the children of the same age. The SPTAN1 gene mutations of the 3 cases were heterozygous mutations, c.6923_6928dup, c.6619_6621delGAG and c.6749T>C, respectively. c.6749T>C was not reported in the previous literature. Thirteen case reports, including 69 patients, were collected. Sixty-seven patients had heterozygous mutations, inherited in an autosomal dominant fashion, including 35 missense mutations, 12 deletion mutations, 11 repetition mutations, 9 nonsense mutations, and the rest 2 patients had compound heterozygous missense mutations. A total of 38 different variation sites were reported. The phenotypes of 69 patients from the previous studies mainly included intellectual impairment (32/69), seizures (30/69), developmental delay (28/69), progressive microcephaly (27/69), hypotonia (23/69), poor visual attention (15/69), spastic quadriplegia (9/69), and gastrointestinal abnormalities (7/69). The primary type of seizures was epileptic spasm. Cranial MRI abnormalities mainly included cerebellar and brainstem atrophy, corpus callosum dysplasia, myelin dysplasia, and brain atrophy. Previous reports showed that a variety of anti-seizure drugs were effective for epileptic seizures. The prognosis varied greatly. Severe cases could be fatal, and mild cases only manifested as mild mental retardation or movement disorders. Conclusions:SPTAN1 gene mutation leads to developmental epileptic encephalopathy type 5, the phenotypes of which include intellectual impairment, global developmental delay, infantile spasms, and head deformity.Antiepileptic drugs and functional training can improve the symptoms, but the prognosis is still poor. This study expands the SPTAN1 gene variant spectrum, enriches the mutant spectrum of SPTAN1 gene associated with developmental epileptic encephalopathy type 5.