Skeletal muscular changes in Pena-Shokeir Sequence

In 1974, PENA and SHOKEIR first described alethal syndrome consisting of facial anomalies(flat and depressed nasal tip, micro- and retro-gnathia, malformed and low-set ears, hypertelo-rism), multiple ankyloses, pulmonary hypoplasiaand camptodactyly. Since then more than 60patients with the Pena-Shokeir sequence havebeen described.In addition to the lesions mentioned above, thefollowing signs were present in most cases: Still-birth or death during delivery or within a fewdays after birth, intrauterine growth retardation,cryptorchidism, polyhydramnios, abnormal pla-centa and short umbilical cord. Familial caseshave been reported.Major congenital malformations of inner organs,however, have been diagnosed in only a fewcases.Pena-Shokeir sequence is now regarded as a he-terogeneous sequence, in which different neuro-muscular lesions may play an important patho-genetic role.In our eight patients with the characteristic find-ings of the Pena-Shokeir sequence an attemptwas made to define more clearly the nature ofskeletal muscular changes observed

Detection of Septata intestinalis in Stool Specimens and Coprodiagnostic Monitoring of Successful Treatment with Albendazole

We describe two patients with AIDS and chronic diarrhea in whom the microsporidian Septata intestinalis was detected with use of light and electron microscopic coprodiagnostic techniques. The ultrastructure of the microsporidian spores found in their stool specimens was distinctly different from that of Enterocytozoon bieneusi, another intestinal microsporidian found in patients infected with human immunodeficiency virus. Electron microscopic examination of duodenal biopsy specimens available from one of the patients enabled identification of S. intestinalis and confirmed the similarity of spores found in feces and in duodenal tissue. Both patients' diarrhea stopped when they were treated with albendazole. Coprodiagnostic monitoring indicated disappearance of the parasites and allowed the diagnosis of a relapse in one patient, who responded well to a second course of treatmen

KIT , PDGFRα and EGFR analysis in nephroblastoma

Nephroblastoma prognosis has dramatically improved, but an unfavourable prognostic subgroup warrants development of novel therapeutic strategies. Selective KIT, PDGFRα and epidermal growth factor receptor (EGFR) tyrosine kinase inhibition evolved as powerful targeted therapy for gastrointestinal stromal tumours and non-small-cell lung cancer. To investigate a potential role for tyrosine kinase inhibition, we analyzed 209 nephroblastomas for immunohistochemical KIT and EGFR expression, 63 nephroblastomas for mutations in KIT exons 9, 11, 13, EGFR exons 18, 19, 20 and 21, and all 209 nephroblastomas for PDGFRα exons 12, 14 and 18. Twenty-two tumours (10.5%) expressed KIT, 31 (14.8%) EGFR, and 10 (4.8%) both KIT and EGFR, respectively. KIT expression was relatively more common among high-risk tumours (6/27; 22.3%) compared to low-/intermediate-risk tumours (26/181; 14.4%). Nine patients deceased, four of which had high-risk tumours with KIT expression in two of four and EGFR expression in one of four. There were no KIT, PDGFRα or EGFR mutations. Our results suggest no significant contribution of KIT, EGFR or PDGFRα mutations to nephroblastoma pathogenesis. Despite a trend towards association of immunohistochemical KIT and EGFR expression with poor outcome in high-risk nephroblastomas, statistical analysis did not yield significant correlations in this subgroup. Therefore, it remains open if KIT, PDGFRα or EGFR tyrosine kinase inhibition constitute a therapeutic target in nephroblastoma in the absence of KIT, PDGFRα or EGFR mutation

Prenatal ultrasonographic diagnosis of holoprosencephaly two cases of cebocephaly and two of cyclopia

Four instances of ultrasonographic detection of holoprosencephaly, one during the second and three during the third trimester of gestation, are reported. Horizontal scans of the skull showed absence of midline structures, communication between the lateral ventricles and reduction of the brain mass, particularly anteriorly. Sagittal scans revealed absence of the nose and presence of a proboscis in the fetuses with cyclopia and hypoplasia of the nose in one cebocephalic fetus. Hypotelorism or a single midline orbit are further pathognomonic features detectable by ultrasound, but only the latter was identified in one of the cyclopic fetuses. Facultative findings of holoprosencephaly identifiable by ultrasound, but absent in our cases, are premaxillary agenesis and bilateral cleft lip and maxilla. The characteristic pattern of ultrasonographic findings in holoprosencephaly should allow an unequivocal prenatal diagnosis during the second and third trimester

Dandy-Walker (like) malformation, atrio-ventricular septal defect and a similar pattern of minor anomalies in 2 sisters: A new syndrome?

We report on sisters with similar craniofacial anomalies, a brain malformation in the area of the posterior fossa, and a congenital heart defect. The craniofacial findings include macrocephaly, a prominent forehead and occiput, foramina parietalia, hypertelorism, downslanting palpebral fissures, a depressed nasal bridge, narrow palate, and apparently low-set ears. Patient 1 had a Dandy-Walker malformation with communicating hydrocephalus, aplasia of the posterior portion of the cerebellar vermis, and high insertion of the confluent sinus, while in patient 2, a Dandy-Walker variant was found with aplasia of the cerebellar vermis and hypoplasia of the hemispheres, large cisterna magna, high insertion of the confluent sinus, but no hydrocephalus. Both sibs were moderately mentally retarded. The older sister had a complete atrio-ventricular canal and died after unsuccessful heart operation at 3 1/2 years. The younger had a successful operation on a cleft mitral valve and septum primum defect. Chromosomes were normal. The occurrence of a distinct and similar pattern of congenital anomalies in sisters born to healthy parents points toward a "new" syndrome caused by the homozygous state of an autosomal recessive gene

Antley‐Bixler syndrome in sisters: A term newborn and a prenatally diagnosed fetus

Sisters with the Antley‐Bixler syndrome are reported herein. The first infant died at 14 days of respiratory failure and the following findings characteristic of the syndrome: craniosynostosis of coronal and lambdoid sutures, brachycephaly, frontal bossing, severe midface hypoplasia with proptosis and choanal stenosis/atresia, humero‐radial synostosis, medial bowing of ulnae, long slender fingers with camptodactyly, narrow iliac wings, anterior bowing of femora, cardiac and renal malformations. Unlike two previously published cases, she did not have connatal fractures, but she had vaginal atresia. Ultrasound examination in a subsequent pregnancy showed immobility at the elbows of the fetus, humero‐radial synostosis, medial bowing of ulnae, and long hands and fingers. The fetus also had mild bowing of femora. The pregnancy was terminated in the 21st week and the findings were confirmed by clinical and radiologic examinations. Additional autopsy findings included cardiac and renal malformations. The Antley‐Bixler syndrome is a recognizable malformation syndrome with a probable autosomal recessive mode of inheritance, which can be diagnosed in the fetus by midtrimester ultrasound examination

Wnt signaling pathway analysis in renal cell carcinoma in young patients

Renal cell carcinomas in young patients constitute a morphologically and genetically heterogeneous group. Twenty percent belong to the newly recognized Xp11.2 translocation-associated family and rare tumors arise from nephroblastoma. Aberrant Wnt signaling through beta-catenin mutation has been implicated in nephroblastoma pathogenesis and has been found to synergize with WT1 mutations. To characterize Wnt signaling activity in renal cell carcinomas in young patients, we gathered 34 tumors (three clear cell, ten Xp11.2 translocation associated, five papillary, two chromophobe, two collecting duct, one neuroblastoma associated, eight unclassified renal cell carcinomas, and three carcinomas combined with nephroblastoma) from patients less than 22 years. Expression of beta-catenin, its homologue gamma-catenin, and of WT1 was assessed by immunohistochemistry in 30 tumors, and sequence analysis of CTNNB1, CTNNG1, and WT1 genes was performed in 25 tumors. Cytoplasmic beta-catenin accumulation was demonstrated in two papillary carcinomas, one neuroblastoma-associated carcinoma, and two carcinomas arising from nephroblastoma. The pattern of gamma-catenin expression paralleled that of beta-catenin but its signal intensity was lower in 22, equal in 7, and stronger only in 1 tumor, respectively. Four tumors showed nuclear WT1 expression. One Xp11.2 translocation-associated carcinoma presented a rare intronic CTNNB1 single nucleotide polymorphism and cytoplasmic beta-catenin accumulation. There were no further CTNNB1 or CTNNG1 sequence alterations. A WT1 mutation was found in the nephroblastoma component of a carcinoma arising from nephroblastoma. These findings suggest Wnt signaling pathway activation only in a minority of renal cell carcinomas in young patients. CTNNB1 mutations are rare events. Cytoplasmic beta-catenin accumulation in an Xp11.2-associated carcinoma suggests potential interaction of Wnt signaling components with microphthalmia transcription factor family also in Xp11.2 translocation carcinomas. WT1 mutation in the nephroblastoma component of a mixed-type renal cell carcinoma provides direct evidence for clonal independence of nephroblastoma and carcinoma components in this exceptional tumor