Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes are promising candidates for new Mendelian traits. One example is early onset hypertension, a rare form of a global cause of morbidity and mortality. We performed exome sequencing of 40 unrelated subjects with hypertension due to primary aldosteronism by age 10. Five subjects (12.5%) shared the identical, previously unidentified, heterozygous CACNA1HM1549V mutation. Two mutations were demonstrated to be de novo events, and all mutations occurred independently. CACNA1H encodes a voltage-gated calcium channel (CaV3.2) expressed in adrenal glomerulosa. CACNA1HM1549V showed drastically impaired channel inactivation and activation at more hyperpolarized potentials, producing increased intracellular Ca2+, the signal for aldosterone production. This mutation explains disease pathogenesis and provides new insight into mechanisms mediating aldosterone production and hypertension.DOI: http://dx.doi.org/10.7554/eLife.06315.001

Mid-aortic syndrome (MAS) is an uncommon condition characterized by narrowing of the abdominal aorta and stenosis of its major branches. Our goal was to illustrate the presentation, diagnosis and management of six new cases of idiopathic MAS together with 96 cases of idiopathic MAS from the literature. The mean age of the 102 cases was 14.3 years (19 days to 49 years). Our patient who presented at 19 days of age is the youngest reported to date. Clinical presentations included hypertension (94%), claudication (17%), renal failure (4%) and intestinal ischemia (1%). Angiography was the diagnostic imaging study of choice. Renal arteries were involved in 91% of patients, while the superior mesenteric artery and celiac artery were involved in 35%. Thirteen percent of cases were managed medically, and the remainder was treated surgically. Our experience shows that initial conservative blood pressure management of idiopathic MAS is feasible unless medical control of hypertension is unsatisfactory, renal function is at risk or there are symptoms of claudication or intestinal ischemia. Careful timing and planning of a surgical intervention is possible for most cases and may, in select cases, be considered after completion of puberty to allow growth to be completed.

COVID-19 is the illness caused by infection with the novel coronavirus SARS-CoV-2. Although myalgia is common in adults, it has not been noted as a common symptom in children. There have been a few reported cases of COVID-19-associated rhabdomyolysis in adults. This case report describes a 16-year-old boy who presented with fever, myalgias, mild shortness of breath with exertion, and dark-colored urine. COVID-19 PCR was positive. His initial creatinine kinase (CK) level was 427,656 U/L. Serum creatinine was normal for age. He was treated with isotonic intravenous fluids containing sodium bicarbonate to maintain urine output of 100-200 mL/h and urine pH > 7.0. His serum creatinine remained normal throughout the hospital stay and he was discharged on hospital day 12 with a CK of 6526 U/L. To our knowledge, no pediatric cases of COVID-19-associated rhabdomyolysis have been previously reported. Adult cases of rhabdomyolysis have been reported and a few reports have noted patients with elevated CK levels without rhabdomyolysis. Given this pediatric case of COVID-19-associated rhabdomyolysis, pediatric clinicians should be aware of this complication and manage fluids appropriately in order to prevent acute kidney injury.

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