Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon.

Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in 2 genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon (HEC) has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a HEC (HEC group) and 39 with a classical postnatal form (CC group). SLC3A1 and SLC7A9 were sequenced. All patients were fully genotyped, and the relationship between the genotype and clinical features was analyzed. We identified mutations in SLC3A1 in 80% of the HEC group and in only 49% of the CC group. The SLC3A1 p.Thr216Met mutation was found in 21% of the alleles in the HEC group but was never found in the CC group. Most of the mutations found in the HEC group were considered severe mutations in contrast with the CC group. Twenty-five novel mutations were reported. This study shows a relationship between genotype and the clinical form of cystinuria, suggesting that only the patients with the most severe mutations presented with an HEC. These results emphasized the need for prenatal cystinuria screening using classical third-trimester ultrasound scan and the early management of suspected newborns.

Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder.

The cobalamin type C deficiency is a rare condition that results from impaired biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Hemizygous mutations of the HCFC1 gene explain the majority of clinically and biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We report a family with two maternal half-brothers with multiple congenital anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with dysmorphic features (flat profile, cleft lip for one), increased nuchal translucency, prenatal onset microcephaly and hypospadias. Additionally to early onset intractable epilepsy and profound neurocognitive impairment, this familial observation suggests that HCFC1 gene should be considered in boys with midline malformations, even without proven cobalamin C deficiency.

[Intra- and interfamilial phenotype variation in Birt-Hogg-Dubé syndrome: Consequences for therapy]. / Variation phénotypique intra- et interfamiliale dans le syndrome de Birt-Hogg-Dubé : conséquences sur la prise en charge.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal-dominantly inherited genodermatosis that predisposes to the development of benign hair follicle tumours, lung cysts, kidney tumours, and possibly colonic cancers, due to mutations in the FLCN gene. We report cases involving a new mutation in three unrelated families. MATERIALS AND METHODS: Blood samples of three probands were submitted for a molecular diagnosis of BHDS. Following DNA extraction, FLCN gene sequencing was performed. The identified mutations were confirmed on a second sample. A cancer genetics consultation was organized and specific tests (dermatological examination, CT scan of chest and abdomen and colonoscopy) were proposed for each BHDS patient. RESULTS: FLCN gene-sequencing analysis revealed an identical complex harmful mutation in all three families. The first proband showed fibrofolliculomas (FF), a history of pneumothorax and colonic adenoma. The mutation was found in a brother and two sisters, who were asymptomatic, and in a niece with FF. The second proband showed FF. The mutation was found in her mother, who had FF. The third proband presented diffuse emphysema and very rare FF. DISCUSSION: This case report shows extremely wide intra- and interfamilial phenotype variation within individuals having a similar FLCN gene mutation. In large cohorts of BHDS patients, no genotype-phenotype correlation has been shown. This case emphasises the vital importance of presymptomatic diagnosis for each member of a BHDS family by means of a cancer genetics consultation, followed by a CT scan of the chest and abdomen, colonoscopy and annual kidney imaging.

Xeroderma pigmentosum group C in a French Caucasian patient with multiple melanoma and unusual long-term survival.

We report the case of an 83-year-old French woman with multiple melanomas showing a severe DNA repair deficiency, corrected after transfection by XPC cDNA. Two biallelic mutations in the XPC gene are reported: an inactivating frameshift mutation in exon 15 (c.2544delG, p.W848X) and a missense mutation in exon 11 (c.2108 C>T, P703L). We demonstrate that these new mutations are involved in the DNA repair deficiency and confirm the diagnosis of xeroderma pigmentosum from complementation group C (XP-C). We speculate that the coexistence of a MC1R variant may be involved in the phenotype of multiple melanomas and that the unusual long-term survival may be related to a lower ultraviolet radiation exposure and to a regular clinical follow-up. This patient appears to be the first French Caucasian XP-C case and one of the oldest living patients with XP reported worldwide.

[Scleroderma-like patch on the thigh in infants after vitamin K injection at birth: six observations]. / Placard sclérodermiforme de la cuisse de l'enfant après injection de vitamine K1 à la naissance: six observations.

INTRODUCTION: Texier's disease or pseudosclerodermatous reaction after intramuscular injection of vitamin K1 is well known in adults although only 1 report of a case in a newborn was found in the literature. We report 6 cases. CASE REPORTS: Six infants (4 boys, 2 girls) developed "peau d'orange" skin lesions after the age of 6 months which was localized in the lower third of the medial aspect of the thigh. Initial rapid locoregional extension was followed by stabilization and then regression. In all 6 cases, histology showed lesions of the fascia and/or the deep hypoderma associated with variable mononuclear inflammatory infiltration and hyalin fibrosis. When performed, immunological studies (complement fixation, search for autoantibodies) were always negative or normal. No visceral involvement was found. DISCUSSION: A pseudosclerodermatous lesion of the lower third of the thigh occurred in 6 infants at the site of an intramuscular injection of vitamin K1 administered at birth. The history, clinical manifestations, histology and outcome of these cases are compatible with the diagnosis of Texier's disease. We discuss the role of the solvent in the Roche vitamin K1 injection. The pathogenesis of this side effect remains unknown. CONCLUSION: Texier's disease in infants after injection of vitamin K1 at birth is a stereotypic dermatosis. Diagnosis is based on history and clinical presentation. The causal effect of injectable vitamin K1 should be entertained whenever pseudosclerodermatous lesions are observed in a young child.

[Reevaluation of environmental factors in allergy to mites: bedding not a factor?]. / Réévaluation des facteurs environnementaux de l'allergie aux acariens: la literie innocentée?

Prospective multicentric study was conducted among parents of children referred in three allergy units. Unlike current opinions: carpets are less frequent in bedrooms of mite's allergic children. foam bedding don't play any role, local humidity non significantly increases the mite's allergy risk. the sunlight absence is significantly correlated with this hypersensitivity. These data, mainly inconsistent with general conviction, could be explained by socio economic diversity of patients.

Comparison of T cell functional changes during childhood with the ontogeny of CDw29 and CD45RA expression on CD4+ T cells.

The ontogeny of the peripheral blood mononuclear cells' responsiveness to various activators during childhood was studied and compared to the expression of CDw29 and CD45RA molecules at the surface of CD4+ T cells. The results show that newborn peripheral blood mononuclear cells are characterized by a responsiveness to mitogens that is higher than that observed in adults, at least shortly after stimulation. This contrasts with a clear decreased response to CD2 and CD3 MAb at any time after stimulation. These functional characteristics correlate with a low density of CDw29 antigen on virtually all CD4+ T cells and a high density of CD45RA antigen on most CD4+ T cells at birth. These patterns of reactivity and phenotype are similar to those found among naive adult T cells. When ageing, the response to mitogens becomes rapidly similar to the adult's values, whereas the responses to CD2 or CD3 MAb are more gradually acquired. This slow rate of functional changes grossly parallels the increase of CDw29+ CD4+ and the decrease of CD45RA+ CD4+ T cell subsets. These changes finally lead to the immunophenotypic and functional characteristics that are typical of adult memory T cells. These results suggest that iterative antigenic stimulations both induce memory T cells and create the conditions to improve the overall immune competence.

[Value of ultrasonic diagnosis in the evaluation of hip dislocation in neonates and infants. Apropos of 340 cases]. / Valeur de l'échographie dans le bilan de la maladie luxante de la hanche du nouveau-né et du nourrisson. A propos de 340 cas.

Ultrasound imaging of hip (UIH) was performed in 170 children (340 hips) with normal (193) and dysplasic (147) hips and findings compared with results of clinical and radiologic examinations. Ultrasound demonstrated 100% sensitivity in cases with abnormal clinical and radiologic finding, and 94% specificity for UIH when clinical and radiologic examinations were negative. Sensitivity and specificity of ultrasound screening (respectively 96 and 81%) were comparatively superior to those of radiography of the pelvis (83 and 78%) in relation to the clinical examinations. These findings predict further development of UIH for screening of congenital dislocation of the hips and for follow up surveillance of treated children.

[Acute necrosis of the thoracic esophagus and ileum complicating rheumatoid purpura]. / Necrose aigue de l'oesophage thoracique et de l'ileon au cours d'un purpura rhumatoide.

A child is described who developed acute ischaemic necrosis of the oesophagus complicating an otherwise typical case of anaphylactoid purpura. This episode was preceded by a necrotising ileitis requiring intestinal resection and ileostomy. The histological similarities of the lesions in the oesophagus and the ileum suggest a common cause connected with the anaphylactoid purpura.