Donor splice-site mutations in WT1 are responsible for Frasier syndrome.

Frasier syndrome (FS) is a rare disease defined by male pseudo-hermaphroditism and progressive glomerulopathy. Patients present with normal female external genitalia, streak gonads and XY karyotype and frequently develop gonadoblastoma. Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by unspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. No case of Wilms' tumour has been reported, even in patients with extended follow-up. In contrast with FS patients, most individuals with Denys-Drash syndrome (DDS; refs 6,7) have ambiguous genitalia or a female phenotype, an XY karyotype and dysgenetic gonads. Renal symptoms are characterized by diffuse mesangial sclerosis, usually before the age of one year, and patients frequently develop Wilms' tumour. Mutations of the Wilms'-tumour gene, WT1, cause different pathologies of the urogenital system, including DDS. WT1 is composed of ten exons and encodes a protein with four zinc-finger motifs and transcriptional and tumour-suppressor activities. Alternative splicing generates four isoforms: the fifth exon may or may not be present, and an alternative splice site in intron 9 allows the addition of three amino acids (KTS) between the third and fourth zinc fingers of WT1 (ref. 17). Here we demonstrate that FS is caused by mutations in the donor splice site in intron 9 of WT1, with the predicted loss of the +KTS isoform. Examination of WT1 transcripts indeed showed a diminution of the +KTS/-KTS isoform ratio in patients with FS.

[Prenatal diagnosis and neonatal management of posterior urethral valves: apropos of 33 case reports]. / Diagnostic ante-natal et prise en charge néo-natale des valves de l'urètre postérieur: à propos de 33 observations.

The existence of valves in the posterior urethra (33 cases) carries a poor prognosis since 25 to 50% of these newborns will develop terminal renal insufficiency. Antenatal diagnosis permits early treatment and should lead to an improved functional prognosis in cases where the number of nephrons is not too low.

Pancreatic venous samplings in infants and children with primary hyperinsulinism.

The authors present 19 cases of hyperinsulinism in children worked up with selective pancreatic venous samplings (PVS). Focal lesions were found in 7, diffuse secretion in 8 and normal insulin levels in 4. In three patients with focal hypersecretion less extensive surgery could be performed and confirmed the presence of focal lesions in two. These preliminary results are encouraging and PVS seems to be a valuable technic for detection of focal lesions in the pancreas of children with hyperinsulinism.

[Congenital hyperparathyroidism. 3 cases]. / Hyperparathyroïdie congénitale. Trois observations.

Hypotonia, neonatal respiratory distress with a chest wall deformity should arouse clinical suspicion to the diagnosis of primary hyperthyroidism. The most common signs at this age are hypercalcaemia, increased alkaline phosphatase, low TRPP and radiological changes especially in the hip. Radio-immunological assay of PTH and plasma concentrations of Vitamin D metabolites are important diagnostic aids but the interpretation of these results should take the clinical and familial context into consideration. Rapid bone structural changes, the resistance of the hypercalcaemia to usual therapeutic measures and the progression to rickets justify urgent surgical treatment. Nearly all cases are due to clear cell hyperplasia.

[Attitude of the pediatric surgeon to antenatal diagnosis of a malformation]. / Attitudes du chirurgien pédiatre face au diagnostic anté-natal d'une malformation.

To have found by prenatal ultrasonography a fetal severe malformation implies a complete collaboration between paediatric surgery who must take a decision and the echographist , the obstetrician, the geneticist. The information they give to the parents is a delicate and necessary step. Four kinds of decisions are discussed (termination, provoked delivery, in utero surgery, secondary neo-natal surgery) at the light of medical, psychological, ethical and juridical data.

[The place of surgery in the treatment of neuroblastoma]. / Place de la chirurgie dans le traitement du neuroblastome.

From 1957 to 1980, 170 neuroblastoma were surgically approached: 3 cervical, 11 thoracic, 147 abdominal, 5 pelvic. The surgical data gathered from this large series leads us to assess that there are great differences between lateral and median neuroblastoma. Lateral ones can be surgically removed without major risk. Median ones arising from sympathetic nerves which depend on the aorta or on the visceral arteries (coeliac or mesenteric) cannot be removed totally without life-threatening risk. These data do not agree with Evans and d'Angio staging. Indeed, stage I and II are only observed in neuroblastomas developed on the lateral nerves of the sympathetic chain and can be removed. Stage III tumors can also be removed surgically when arising from a lateral site, even if they cross the median line. On the contrary all median perivascular neuroblastomas are to be staged III: total removal is not possible and the surgical risk is too high when compared with efficiency of chemotherapy. A special type, the distal perivascular neuroblastoma, is pointed out (5 cases). It is very important to precise exactly the initial localization of neuroblastoma, whatever be their metastatic extension. The new technics of investigation (C.T., ultrasonography, but also plain film and front and lateral views of intravenous pyelogram) allow to define precisely the median or lateral site of the tumor and also to choose between a non-surgical (median) or a surgical (lateral) treatment. This distinction seems in correlation with the two different ways of pathway of the embryonic neuroblast cells.

Radiological aspects of the small bowel after extensive resection in children.

The authors present radiological aspects of small bowel after extensive resection. They describe the main phenomena related to compensatory hypertrophy: dilatation of the loops, mucosal fold-thickening and motor disturbances. The main complications demonstrated by the radiological examination are presented; gallstones, non-functioning anastomosis, bacterial overgrowth.

Enterocutaneous fistulas of the small bowel in children (25 cases).

During the past 5 yr, 25 children ranging in age from 10 days to 14 yr have been treated for single or multiple severe enterocutaneous fistulas. There were two deaths. In 24 cases out of 25, initial treatment was nonsurgical and consisted of nutritional support (by total parenteral nutrition in 20, and constant rate enteral feeding in 4) and was associated with local treatment. Successful closure was achieved without surgery in 13 cases, and 11 secondary operations were performed, with success in 9. The addition of nutritional methods has completely changed the prognosis of enterocutaneous fistula.