PHYSICAL THERAPY INTERVENTION FOR PATIENT WITH EAST SYNDROME- A CASE STUDY.

EAST syndrome is autosomal recessive disorder due to mutations in gene KCNJ10, a gene encoding a potassium channel expressed in the brain, eye, ear and kidney. It is characterized by four cardinal features; Epilepsy, Ataxia, Sensorineural deafness, and renal salt-wasting Tubulopathy, thus the acronym EAST syndrome. It was rst described as a distinct clinical entity in 2009 by Bockenhauer and scholl, who named this condition EAST syndrome and SeSAME syndrome for Seizures, Sensorineural deafness, Ataxia, Mental retardation and Electrolyte imbalance respectively. Neurodevelopmental delay is evident in most patients with EAST syndrome that were old enough to be assessed; Thus, physiotherapy intervention also plays a vital role in EAST syndrome along with medical management. From physiotherapy perspective; symptomatic management to Improve overall health, wellbeing and motor control becomes ultimate goal in the patient with EAST syndrome. As there is no specic physical therapy treatment approach and no specic tool to evaluate function for children with EAST syndrome; for clinically presented delay development and ataxia, Neurodevelopment therapy (NDT) was utilized as treatment approach and Gross motor function measure (GMFM) & Gross motor performance measure (GMPM) were utilized for assessment in this case study to track progress on follow ups. Result showed marked improvement in GMFM and GMPM scores at follow ups and concluded that Physical therapy intervention improves the gross motor function as well as gross motor performance in patient with EAST syndrome.

Potassium conservation is impaired in mice with reduced renal expression of Kir4.1

To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wk, however, limits the usefulness of this model, so we developed a kidney-specific Kir4.1 “knockdown” mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology. These mice appeared normal and survived to adulthood. Kir4.1 protein expression was decreased ~50% vs. wild-type (WT) mice by immunoblotting, and immunofluorescence showed moderately reduced Kir4.1 staining in distal convoluted tubule that was minimal or absent in connecting tubule and cortical collecting duct. Under control conditions, the ksKD mice showed metabolic alkalosis and relative hypercalcemia but were normokalemic and mildly hypermagnesemic despite decreased NCC expression. In addition, the mice had a severe urinary concentrating defect associated with hypernatremia, enlarged kidneys with tubulocystic dilations, and reduced aquaporin-3 expression. On a K/Mg-free diet for 1 wk, however, ksKD mice showed marked hypokalemia (serum K: 1.5 ± 0.1 vs. 3.0 ± 0.1 mEq/l for WT), which was associated with renal K wasting (transtubular K gradient: 11.4 ± 0.8 vs. 1.6 ± 0.4 in WT). Phosphorylated-NCC expression increased in WT but not ksKD mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in impaired K conservation, which appears to be mediated by reduced expression of activated NCC.