Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription factor expressed in tissues including renal epithelia, associate with abnormal renal development. While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and hypomagnesemia. We retrospectively reviewed radiographic and laboratory data for all patients from a single center who had been screened for an HNF1B mutation. We found heterozygous mutations in 21 (23%) of 91 cases of renal malformation. All mutation carriers had abnormal fetal renal ultrasonography. Plasma magnesium levels were available for 66 patients with chronic kidney disease (stages 1 to 3). Striking, 44% (eight of 18) of mutation carriers had hypomagnesemia (Ͻ1.58 mg/dl) compared with 2% (one of 48) of those without mutations (P Ͻ 0.0001). The median plasma magnesium was significantly lower among mutation carriers than those without mutations (1.68 versus 2.02 mg/dl; P Ͻ 0.0001). Because hypermagnesuria and hypocalciuria accompanied the hypomagnesemia, we analyzed genes associated with hypermagnesuria and detected highly conserved HNF1 recognition sites in FXYD2, a gene that can cause autosomal dominant hypomagnesemia and hypocalciuria when mutated. Using a luciferase reporter assay, we demonstrated HNF1B-mediated transactivation of FXYD2. These results extend the phenotype of HNF1B mutations to include hypomagnesemia. HNF1B regulates transcription of FXYD2, which participates in the tubular handling of Mg 2ϩ , thus describing a role for HNF1B not only in nephrogenesis but also in the maintenance of tubular function.

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Design Prospective audit of first six months. Setting Referral from a district general hospital on the Isle of Wight to a comprehensive tertiary referral service, the Centre for Fetal Care at Queen Charlotte's Hospital 120 km away in London. Participants Women whose pregnancy was suspected, or at risk, of fetal abnormality. Interventions Remote consultation by transmitting ultrasound and video in real‐time over ISDN 30 telephone lines. Contemporaneous questionnaire to referring practitioner and patient. Main outcome measures Frequency, indication, technical success and duration of consultation. Qualitative and semi‐quantitative image quality. Effect of teleconsultation on need for physical referral. Results Twenty‐nine women underwent 39 teleconsultations, and image quality was sufficient for diagnosis in all but one. Fetal abnormalities were present in 76%. Referral in person was required for only four women, significantly fewer than the 13 the referring hospital indicated would have been physically referred in the absence of this service (P < 0.001). Most mothers were counselled by the specialist ‘face‐to‐face’ over the link, and 80% felt teleconsultation reduced their anxiety. Conclusions A fetal telemedicine service is technically and clinically feasible. This demonstration suggests that such a service reduces the need for physical referral while increasing the rate of consultation, allowing better selection of patients who might benefit from referral. Further evaluation in a variety of clinical settings is now indicated, along with cost‐benefit analysis.

The antenatal histories of 42 patients with posterior urethral valves diagnosed between June 1987 and September 1990 were reviewed. The mothers of all patients had at least one ultrasound scan during pregnancy. Despite this, fetal uropathy was diagnosed in only 19 cases. The remaining 23 undiagnosed children presented acutely, all within the first 6 months of life. In 33 of 36 pregnancies scanned before 24 weeks' gestation, fetal urological pathology was undetected. Mean plasma creatinine (pCr) at presentation in the group antenatally diagnosed was 139 mumol/l and in those presenting acutely was 238 mumol/l. All pCr analysed were taken after at least 48 h of life. Renal function as measured by follow-up pCr was better in the antenatally diagnosed group during the first year of life. It would appear that a routine second ultrasound scan at 26 weeks' gestation or later would reveal more cases of posterior urethral valves and this information may improve the outcome in terms of renal function.

There are few studies on visceral pain in infants, despite its clinical importance. We have used the abdominal skin reflex (ASR) to measure changes in abdominal sensitivity in the presence of visceral pathology in infants. The reflex was elicited by applying calibrated von Frey hairs to each side of the abdomen and the mechanical threshold and the degree of reflex radiation as denoted by hip flexion were measured. The developmental progression of ASR properties during the first year of life was studied in a cross-sectional sample of healthy infants ranging from 30 to 95 weeks postconceptional age (PCA). These properties were compared to those in infants with unilateral hydronephrosis (UH) using a blinded protocol. Infants with UH were studied at their first outpatient appointment after birth, and postoperatively following surgery if this was indicated. The investigators were blinded to laterality and severity of hydronephrosis until data were analysed, or until surgery. A total of 30 patients with UH and 77 healthy infants were included in the study. In 21 (70%) patients, the side of hydronephrosis had a significantly lower ASR threshold than the contralateral side of the abdomen. There was a significant increase in reflex threshold and decrease in reflex radiation with increasing PCA in control infants. However, in UH infants, this relationship did not exist, even on the unaffected side of the abdomen.Our results show that infants with prenatally diagnosed UH demonstrate increased abdominal sensitivity compared with control infants. Using the ASR, we have provided the first evidence of referred visceral hypersensitivity in infants.

Objective To examine, in infants presenting with vesico‐ureteric reflux (VUR), the relationship between the presence of initial renal abnormalities with the outcome of VUR and bladder function at 16 months of age. Patients and methods The study group comprised 40 infants (32 boys) presenting consecutively (29 after prenatal detection) with VUR grade III or greater (bilateral in 29) on the initial micturating cystogram (median age 8 weeks). The initial presence of abnormal kidneys was determined from isotopic renography and/or ultrasonography. These data were correlated with the outcome of VUR, from direct isotope cystography, and bladder function assessed by natural filling urodynamics, examined at age 16 months (mean 16.4 months, sd 2.1). Results Three groups were identified. Group 1 (eight boys and six girls) had normal kidneys bilaterally; initially grade III VUR was common. At 16 months bladder function was normal in 10 children and none had VUR (complete resolution). Group 2 (14 boys and two girls) had unilateral renal abnormalities; initially VUR was predominantly grade IV or grade V. At 16 months bladder function was normal in eight children and VUR resolved in eight, five of these with normal bladder function. Group 3 (10 boys) had bilateral renal abnormalities. Initially grade V VUR predominated; at 16 months the bladder function was normal in only one, and in the rest the emptying dynamics were abnormal. All 10 boys had persisting VUR (no resolution). Conclusions In infants with moderate or severe VUR, resolution at 16 months old is associated with normal kidneys in a similar proportion of boys and girls. Resolution also correlates well with normal bladder function. Presentation in infancy with bilateral abnormal kidneys, associated with severe VUR in boys, is a poor prognostic sign for the early outcome of VUR and for bladder function.