Are Mutations in the DHRS9 Gene Causally Linked to Epilepsy? A Case Report.

The DHRS9 gene is involved in several pathways including the synthesis of allopregnanolone from progesterone. Allopregnanolone is a positive modulator of gamma aminobutyric acid (GABA) action and plays a role in the control of neuronal excitability and seizures. Whole-exome sequencing performed on a girl with an early onset epilepsy revealed that she was a compound heterozygote for two novel missense mutations of the DHRS9 gene likely to disrupt protein function. No previous studies have reported the implication of this gene in epilepsy. We discuss a new potential pathogenic mechanism underlying epilepsy in a child, due to a defective progesterone pathway.

Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency.

Succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of γ-aminobutyric acid (GABA) metabolism, manifests typically as a nonprogressive neurodevelopmental disorder with cognitive deficiency, neuropsychiatric morbidity and epilepsy. Therapy targets symptomatic seizures and neurobehavioral disturbances. We report an adolescent female with SSADHD whose unresponsiveness to a broad spectrum of antiepileptics was circumvented with magnesium valproate (MgVPA). Epilepsy remains well controlled in our patient, with concomitant improvements in behavioral symptoms and an absence of adverse symptoms. MgVPA intervention may have utility in SSADHD.

Anti-N-methyl-D-aspartate-receptor encephalitis: cognitive profile in two children.

BACKGROUND: Anti-N-Methyl D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder associated with antibodies against NMDAR resulting in a characteristic neuropsychiatric syndrome characterized by seizures, dyskinesias, and cognitive impairment. The extent and specific tasks associated with cognitive dysfunction in anti-NMDAR encephalitis have not been fully investigated. AIMS: To describe cognitive and neuropsychological profile in two children with anti-NMDAR encephalitis. METHODS: Clinical, laboratory, cognitive and neuropsychological assessments have been performed. Cognitive functions have been evaluated one year after the disease onset, at age 4 years and 10 months in one patient and at age 5 years and 5 months in the other subject. The first patient has been re-assessed one year after the first evaluation. RESULTS: Both children, who were reported to be normal before disease onset, showed a severe neurological impairment during the acute phase of disease with progressive substantial recovery following treatment. Selective and prolonged attention, activation and integration of semantic information and verbal fluency were particularly impaired. Significant improvements were observed at neuropsychological re-assessment. CONCLUSIONS: Executive dysfunction seems to be the "core" of the neuropsychological profile of children with anti-NMDAR encephalitis. Cognitive abilities may be, at least to some extent, recovered providing that immunomodulatory treatment and specific psychomotor and pedagogical therapy are started soon after disease onset.