Background: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited.

This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.

This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.

Background/Aims: Mutations in the inwardly-rectifying K⁺-channel KCNJ10/Kir4.1 cause autosomal recessive EAST syndrome (epilepsy, ataxia, sensorineural deafness and tubulopathy). KCNJ10 is expressed in the distal convoluted tubule of the kidney, stria vascularis of the inner ear and brain glial cells. Patients diagnosed clinically with EAST syndrome were genotyped and mutations in KCNJ10 were studied functionally. Methods: Patient DNA was amplified and sequenced, and new mutations were identified. Mutant and wild-type KCNJ10 constructs were cloned and heterologously expressed in Xenopus oocytes. Whole-cell K⁺ currents were measured by 2-electrode voltage clamping and channel expression was analysed by Western blotting. Results: We identified 3 homozygous mutations in KCNJ10 (p.F75C, p.A167V and p.V91fs197X), with mutation p.A167V previously reported in a compound heterozygous state. Oocytes expressing wild-type human KCNJ10 showed inwardly rectified currents, which were significantly reduced in all of the mutants (p < 0.001). Specific inhibition of KCNJ10 currents by Ba²⁺ demonstrated a large residual function in p.A167V only, which was not compatible with causing disease. However, co-expression with KCNJ16 abolished function in these heteromeric channels almost completely. Conclusion: This study provides an explanation for the pathophysiology of the p.A167V KCNJ10 mutation, which had previously not been considered pathogenic on its own. These findings provide evidence for the functional cooperation of KCNJ10 and KCNJ16. Thus, in vitro ascertainment of KCNJ10 function may necessitate co-expression with KCNJ16.

Faecal incontinence and constipation are well known problems in children with spina bifida. Effective treatment can be difficult and this gave the condition a low priority despite the obvious physical and psychological sequelae. Positive experience with colonic enemas (CE) in the paediatric post-operative care have led us to adopt this method as the treatment of choice for defecation disorders in children with spina bifida. In 41 spina bifida children (mean age 8.4 years, range 7 months to 22 years), retrograde CEs with hand-warm tap water were given at home from once a day to twice per week. Satisfaction with the procedure was evaluated with a questionnaire sent out after a mean follow-up period of 33 months (range 6 to 55 months). The indications to start CEs were faecal incontinence (27%), constipation (27%) or both. 34% of 41 children also had other gastrointestinal complaints, 7% had headaches, 29% had poor appetite and 15% felt generally unwell. Before the start of CE 22% of the children had been on a diet, 37% on oral laxatives, 31% on a rectal laxative and 44% had to have manual evacuations. 90% used diapers on a daily basis. At the end of the follow-up period 27% of the children were still on a diet and 17% still used oral laxatives but rectal laxatives were no longer used nor were manual evacuations necessary. 66% of the 41 children were completely faecally continent and constipation occurred only occasionally, no child had faecal retention or impaction. At follow-up 39% still used diapers regularly and 20% used a panty-line and complaints of abdominal pain, headache and poor appetite were rare. Satisfaction with the procedure was rated highly by 63% of parents and children and good by 37% but 15% of the children found regular CEs painful. It is concluded from the study that CEs are therapeutically effective in the treatment of both faecal incontinence and constipation in children with spina bifida. The procedure is well tolerated even by very young children. Long-term histopathological effects of daily CEs on the lower gastrointestinal tract needs to be evaluated by future research.