Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the early-onset epileptic syndromes characterized by migrating polymorphous focal seizures. Whole exome sequencing (WES) in ten sporadic and one familial case of EIMFS revealed compound heterozygous SLC12A5 (encoding the neuronal K+-Cl− co-transporter KCC2) mutations in two families: c.279 + 1G > C causing skipping of exon 3 in the transcript (p.E50_Q93del) and c.572 C >T (p.A191V) in individuals 1 and 2, and c.967T > C (p.S323P) and c.1243 A > G (p.M415V) in individual 3. Another patient (individual 4) with migrating multifocal seizures and compound heterozygous mutations [c.953G > C (p.W318S) and c.2242_2244del (p.S748del)] was identified by searching WES data from 526 patients and SLC12A5-targeted resequencing data from 141 patients with infantile epilepsy. Gramicidin-perforated patch-clamp analysis demonstrated strongly suppressed Cl− extrusion function of E50_Q93del and M415V mutants, with mildly impaired function of A191V and S323P mutants. Cell surface expression levels of these KCC2 mutants were similar to wildtype KCC2. Heterologous expression of two KCC2 mutants, mimicking the patient status, produced a significantly greater intracellular Cl− level than with wildtype KCC2, but less than without KCC2. These data clearly demonstrated that partially disrupted neuronal Cl− extrusion, mediated by two types of differentially impaired KCC2 mutant in an individual, causes EIMFS.

Objectives: Parents who have children with complex lifelong and life-limiting neurological conditions experienced many stresses and anxieties throughout their lives as caregivers. However, this information is still very limited. The study aimed to explore the challenges faced by parents with children who have complex neurological conditions, their coping strategies, needs, and expectations. Materials and Methods: A semi-structured, in-depth interviews were conducted in the either Malay or English language among the parents of children with complex lifelong neurological conditions and have been on long-term in-patient hospital care. The interviews were audio-recorded and transcribed for thematic analysis. The qualitative study was conducted from October to November 2016 at the Paediatric Institute of Hospital Kuala Lumpur. Grounded theory was used to examine the qualitative data with inductive and deductive types of coding. The transcripts were read repeatedly to allow familiarity to the themes presented by the participants. Further discussions were conducted among the researchers to triangulate the information. Results: A total of 11 parents were interviewed for this study. The thematic analysis resulted in 8 challenges: Physical wellbeing, Environment, Relationship, Financial, Occupational, Rational, Mental, and Spiritual. Coping strategies comprised problem focused issues related to the key challenges in the caregivers’ context. Similar to the needs and expectations, the key themes were derived from the key understandings of the challenges and looking at the palliative care impacts for these children. Conclusion: There are various challenges faced by parents of children with life-limiting neurological disorders. Physical, Environment, Relationship, Financial, Occupational, Rational, Mental, and Spiritual Wellbeing can be a platform for the assessment of the caregivers’ needs and the planning for palliative care support.

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