Mutations in ACTA2 (smooth muscle cell-specific isoform of aactin) lead to a predisposition to thoracic aortic aneurysms and other vascular diseases. More recently, the ACTA2 R179H mutation has been described in individuals with global smooth muscle dysfunction. We report a patient heterozygous for the mutation in ACTA2 R179H who presented with megacystis at 13 weeks gestational age and, at birth, with prune-belly sequence. He also had deep skin dimples and creases on his palms and soles, a finding not previously described but possibly related to ACTA2. To our knowledge, this is the first report of the R179H mutation in ACTA2 in a child with prune-belly sequence. We think the R179H mutation in ACTA2 should be included in the differential diagnosis of individuals presenting with the sequence without an identified mechanical obstruction. Furthermore, as ACTA2 R179H has been reported in patients with severe vasculomyopathy and premature death, we recommend that molecular testing for this mutation be considered in fetuses presenting with fetal megacystis with a normal karyotype, particularly if the bladder diameter is 15 mm or more, to allow expectant parents to make an informed decision.

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Background: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. Methods: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. Results: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5−/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. Conclusions: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.

Background Autosomal‐recessive renal tubular dysgenesis (AR‐RTD) is a rare genetic disorder caused by defects in the renin‐angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period. Methods Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes. Results While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors. Conclusion While AR‐RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision‐making.