Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

[Candida glabrata chorioamnionitis following in vitro fertilization]. / Chorioamniotite à Candida glabrata après fécondation in vitro.

We report one case of severe Candida glabrata chorioamnionitis and septicemy occurring in a twin pregnancies achieved by in vitro fertilization techniques which resulted in pregnancy loss after preterm rupture of the membrane at 22 weeks of gestation despite a treatment with amphotericin B.

Stability of the m.8993T->G mtDNA mutation load during human embryofetal development has implications for the feasibility of prenatal diagnosis in NARP syndrome.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations cause a wide range of serious genetic diseases with maternal inheritance. Because of the high transmission risk and the absence of therapy in these disorders, at-risk couples often ask for prenatal diagnosis (PND). However, because heteroplasmy load (coexistence of mutant and wild-type mtDNA) may vary among tissues and with time, the possibility that a single fetal sample may not reflect the whole neonate impedes prenatal diagnosis of mtDNA diseases. METHODS: We performed 13 prenatal diagnoses for the NARP (neurogenic weakness, ataxia, retinitis pigmentosa) m.8993T-->G mtDNA mutation (p.Leu156Arg) in the ATP synthase subunit 6 gene. Analyses were performed on chorionic villous (CVS) and/or amniocyte samples carried out at various stages of pregnancy, using a method enabling quantification of low DNA amounts. RESULTS: Maternal mutant loads ranged from 0 to 75% in blood and had no predictive value for the fetus status, except for women with no detectable mutant DNA, whose fetuses were consistently mutation-free. In 8/13 PND, mutant load was <30%. These children are healthy at 2-7 years of age. In 5/13 PND, mutant load ranged from 65 to 100%, and parents preferred to terminate the pregnancies (15-22 weeks of gestation). Single-cell analysis of 20 trophoblastic cells and 21 amniocytes isolated from two affected fetuses found an average mutant load close to the overall CVS and amniocyte mutant load, despite striking intercellular variation. The m.8993T-->G mutant loads, assessed in 7, 17, 11, and 5 different tissues from 4 terminations, respectively, were identical in all tissues from a given individual (mean (SD) 78 (1.2)%, 91 (0.7)%, 74 (2)%, and 63 (1.6)% for the 4 fetuses, respectively). CONCLUSIONS: Our results indicate that the placental/amniotic mutant loads do reflect the NARP mutant mtDNA load in the whole fetus, even when the sample amount is small, and suggest that heteroplasmy level remains stable during pregnancy, at least after 10 weeks of gestation. Although these data establish the feasibility of PND for this mutation, assessing more precisely the correlation between mutant load and disease severity should further help in interpreting PND results.

De novo subtelomeric deletion additional to an inherited apparently balanced reciprocal translocation.

OBJECTIVE: We describe the analysis of an apparently balanced inherited reciprocal translocation in a fetus presenting with multiple congenital abnormalities, characterize the structural chromosome rearrangement, and report an unexpected additional imbalance to the inherited rearrangement. METHODS: DNA microarray was used to screen for genomic imbalance in subtelomeric and interstitial critical regions. High-resolution comparative genomic hybridization was used to screen for genomic imbalance at a genome-wide level. Fluorescence in situ hybridization using whole-chromosome painting and specific probes was used to characterize the inherited translocation, and the size of the de novoadditional deletion. RESULTS: An unexpected additional deletion was found in 7qter on derivative 10 of the inherited maternal reciprocal translocation t(7;10)(q11.23; p14). CONCLUSIONS: We show the usefulness of genome-wide and specific molecular cytogenetic techniques to explore apparently balanced rearrangements.

Specific osseous spurs in a lethal form of hypophosphatasia correlated with 3D prenatal ultrasonographic images.

BACKGROUND: Hypophosphatasia is an osseous dysplasia with highly variable clinical expression, ranging from a recessive lethal prenatal type to late onset dominant short stature with premature shedding of teeth. Lethal forms of hypophosphatasia include short limb dwarfism with lack of ossification, especially on the vertebral bodies, very slender ribs and clavicles, and bowed, short lower extremities, with a bifid aspect of the diaphyses. Alkaline phosphatase is abnormally low in liver, bone, kidney and plasma. METHODS: We present here the prenatal images of a lethal form of hypophosphatasia, diagnosed precociously because of specific osseous spurs in a context of recurrent short limb dwarfism. RESULTS: Prenatal 3D ultrasonography has shown these spurs as early as 18 weeks. Molecular biology found compound heterozygous mutations in the gene TNSALP. CONCLUSION: In a context of short limb dwarfism, the search for these specific osseous spurs orient strongly toward the diagnosis of lethal hypophosphatasia.

Prenatal forehead edema in 4p- deletion: the 'Greek warrior helmet' profile revisited.

OBJECTIVES: Deletion of short arm of chromosome 4 is difficult to ascertain prenatally, and can be missed. METHODS: A prenatal suspicion of 4p- syndrome was thoroughly investigated by using two-dimensional and three-dimensional sonography, with a description of the fetal face dysmorphological pattern. The cytogenetic confirmation, obtained by karyotype and FISH technique, allowed a precise description of the prenatal abnormalities. Post-termination tridimensional helicoidal scanner of the fetal face was performed. RESULTS: The main anomaly discovered using two-dimensional sonography was the presence of a strikingly thick prefrontal edema (8 mm, twice the normal values, at 22 weeks: 3.81 +/- 0.62 mm). Three-dimensional sonography showed the classical postnatal profile, with the phenotypic aspect of a 'Greek warrior helmet'. Nasal bones were normal in size and placement, confirmed by helicoidal scanner. CONCLUSION: Prenatal diagnosis of 4p deletion syndrome can be difficult, and it is the presence of prefrontal edema, associated with more subtle facial anomalies (short philtrum, microretrognathia) which should trigger cytogenetic investigation for 4p- deletion, even with only borderline growth retardation.

Classical West "syndrome" phenotype with a subtelomeric 4p trisomy.

We report a girl with mild mental retardation with onset of infantile spasms at age of 9 months. Treatment with a short course of adrenocorticotropic hormone (ACTH) was successful. Initially, a diagnosis of idiopathic West syndrome, with good neurological outcome and disappearance of epilepsy after treatment, was made. Conventional karyotype was normal. Reinvestigations were done at age 8 years, because of a new pregnancy. Karyotyping of both parents was done because of mild dysmorphic features in the proband, and to eliminate other causes than early age epilepsy as the etiology of her mental retardation. Parental karyotypes showed a balanced paternal translocation (4p;17q) resulting in partial 4p trisomy, without significant 17q monosomy in the proband. Chromosomal abnormalities usually lead to a severe West syndrome with poor prognosis of neurological outcome (persistent severe epilepsy, mental retardation, and behavioral disturbances). The presence of an undetected cytogenetic anomaly in our proband with transient hypsarythmia is unusual and led us to propose systematic telomeric screening in apparently "idiopathic" West syndrome patients with mild mental retardation and subtle dysmorphic features.

[Fenofibrate-induced acute hepatitis with pseudo-cholangitis]. / Hépatite aiguë pseudo-angiocholitique au fénofibrate.

We report the case of acute hepatitis probably due to fenofibrate. Clinical features included abdominal pain and fever. Serum aminotransferases and alkaline phosphatase activities were moderately increased. Rechallenge induced a relapse of the symptoms and liver test abnormalities. High levels of eosinophils were present in the blood and in the liver suggesting an immunoallergic mechanism. Fenofibrate withdrawal was rapidly followed by favorable outcome.

[Nodular regenerative hyperplasia and primary biliary cirrhosis]. / Hyperplasie nodulaire régénérative et cirrhose biliaire primitive.

We report two cases of nodular regenerative hyperplasia of the liver associated with primary biliary cirrhosis. Cholestasis and presence of antimitochondrial antibodies were noted in both patients. In one patient, the diagnosis of nodular regenerative hyperplasia was supported by the demonstration of disseminated small hepatic nodules without perinodular fibrosis. Twelve years later, the histopathological picture was one of primary biliary cirrhosis. The other patient presented an histological picture of regenerative hyperplasia of the liver and primary biliary cirrhosis. The association of regenerative hyperplasia of the liver and primary biliary cirrhosis is discussed.

Presence of papilloma virus type 11 in condyloma acuminatum of bladder in female renal transplant recipient.

A case is reported of a female renal transplant recipient in whom, after two years of immunosuppression, condylomata acuminata of the genital tract with urethral and bladder extension developed. The condyloma of the bladder was resected endoscopically with no relapse. Virologic examination revealed a human papilloma virus type 11.

[Carcinosarcomas of the bladder. Immunohistochemical study in 3 cases]. / Carcinosarcomes de vessie. 3 cas avec étude immunohistochimique.

We present 3 cases of carcinosarcoma of the bladder. We discuss the value of histochemistry on their diagnosis. We compare them to similar tumors reported in the medical literature. Like fusocellular carcinoma, carcinosarcoma finally appear as a morphological variant of high grade urothelial carcinoma, often difficult to diagnose. With our present knowledge, it is not possible to propose for these tumors other therapeutic measures than those already in use for high grade urothelial malignancies, based on the level of infiltration in the bladder wall. The classic pejorative prognosis of these tumors is contradicted by the favorable evolution in some cases reported in medical literature.

Hepatoblastoma and hepatocarcinoma in children: analysis of a series of 29 cases.

Twenty-nine cases of liver malignancies, 26 hepatoblastomas (HB) and 3 hepatocarcinomas (HC), were treated in a 13-year period. All children were submitted to operation but four had nonresectable tumors, even after chemotherapy. Surgery in the 25 cases consisted of right lobectomy in 14, a left lobectomy in 9, and a tumorectomy in 2; a secondary operation had to be performed in 5 cases, either because of histologic doubt on the cut section of the presumed normal parenchyma, or for local recurrence. Preoperative chemotherapy, instituted on a routine basis since 1982, did appear to facilitate surgery in otherwise inoperable tumors. The benefits of preoperative embolization, done for three children, were minimal. Ten children died, one in the immediate postoperative period, eight others from the disease, and one from a complication of chemotherapy. Follow-up for the 18 surviving children, all recurrence and metastasis-free, with normal alphafetoprotein (AFP) is less than 2 years for four and from 2 to 11 years for 14. One teen-age girl, with a fibrolamellar carcinoma has just recently been reoperated because of recurrence three years later. In spite of the fact that 6 out of 7 children operated without adjunctive treatment are cured, a systematic course of preoperative chemotherapy has been prescribed in the more recent cases. Follow-up for these is yet too short.

[Right endocarditis in disseminated aspergillosis]. / Endocardite droite au cours d'une aspergillose disséminée.

A 53 year old man with an anaplastic bronchial carcinoma was hospitalised for septic shock and acute respiratory distress after a cutaneous, probably staphylococcal infection, and died in spite of anti-staphylococcal antibiotherapy. The autopsy showed pulmonary, cardiac, cerebral and renal aspergillosis. A right heart aspergillous endocarditis, very rare in this pathology, was also discovered but there were no cardiac valves lesions. The patient was in an "immunodepressed" state as usually observed in pulmonary aspergillosis. The endocardial localisation of aspergillosis and the "pseudo-miliary" appearances of the pulmonary lesion indicated an extra-pulmonary portal of entry, cutaneous or intravenous which is unusual in this pathology. This hypothesis is supported by previous reports of pulmonary aspergillosis where right heart endocarditis is exceptionally rare and by aspergillous left heart endocarditis after open heart surgery where pulmonary aspergillosis is absent.

[A non-secreting bladder paraganglioma. A case report]. / Paragangliome vésical non sécrétant. Une observation.

The authors report the case of a 43 year old patient hospitalized for hematuria extending over eight years. Cystoscopy revealed an endovesical lesion which was resected and diagnosed as a non-secreting vesical paraganglioma. At operation, the cervical localization of the lesion was treated by total cystoprostatectomy. Starting out from this case report, the authors discuss the difficulties of diagnosing non-secreting vesical paragangliomas, the difficulties of assessing their malignancy and therefore the difficulties of treating them.

[Fetus in fetu: report of 2 cases and analysis of the literature]. / Foetus in foetu: rapport de 2 cas et analyse de la littérature.

Foetus in foetu is a very unusual cause of abdominal mass in the infancy. Twenty cases only have been quoted in the literature. Two others cases are added, concerning two girls: a three months infant, second born from a genuine twin pregnancy, and a four weeks newborn whose the mass was discovered before the birth, on routine ultrasonography. In together, the diagnosis was made in operating room, then confirmed by pathologic studies. Literature data are recorded, and the difference between teratomas and foetus in foetu is point. The pathogeny remains obscure. It could result from the inclusion of a parasite twin in his bearer, become during embryologic stage of the delimitation.

[A case of pseudotumorous pulmonary cryptococcosis]. / Un cas de cryptococcose pulmonaire pseudo-tumorale.

A case of pseudotumorous pulmonary torulosis (or toruloma) clinically suggestive of protracted pneumopathy is reported. The main pathological, clinical and histological forms of this mycotic infection are recalled. The pathologist plays an essential part in the diagnosis of toruloma since the fungus can be demonstrated in bronchial biopsy specimens, bronchial aspirates and sputum.