Isabella Moore

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy

Objective To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia.

Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11-negative PJS cases.

Germ‐line mutations in the serine‐threonine kinase gene STK11 (LKB1) cause Peutz–Jeghers syndrome (PJS), a rare autosomal dominantly inherited disease, characterized by hamartomatous polyposis and mucocutaneous pigmentation. STK11 mutations only account for about half of PJS cases, and a second disease locus has been proposed at chromosome segment 19q13.4 on the basis of genetic linkage analysis in one family. We identified a t(11;19)(q13;q13.4) in a PJS polyp arising from the small bowel in a female infant age 6 days. Because the breakpoint in 19q13.4 may disrupt the putative PJS disease gene mapping to this region, we mapped the breakpoint and analyzed DNA from the case and a series of STK11‐negative PJS cases. Using two‐color interphase fluorescence in situ hybridization, the breakpoint region was refined to a 0.5‐Mb region within 19q13.4. Eight candidate genes mapping to the breakpoint region—U2AF2, EPN1, NALP4, NALP11, NALP5, ZNF444, PTPRH, and KIAA1811—were screened for mutations in germ‐line and polyp DNA from the case and from 15 PJS cases that did not harbor germ‐line STK11 mutations. No pathogenic mutations in the candidate genes were identified. This report provides further evidence of the existence of a second PJS disease locus at 19q13.4 and excludes involvement of eight candidate genes.

Extending the overlap of three congenital overgrowth syndromes

We present the case of a male infant, born prematurely (at 33 weeks gestation) with macrosomia, disproportionate macrocephaly, facial dysmorphism, short penis and a small umbilical defect. He had a large ASD and was ventilated from birth for respiratory distress syndrome. He died at 12 hours of age despite neonatal ITU care. Post‐mortem examination showed highly lobulated kidneys with nodules of blastema and foci of hamartomatous change in the medulla. Prominence of pancreatic islet cells and expansion of hepatic portal tracts were also noted. His mother has minor cervical spine abnormalities. We discuss the differential diagnosis and the difficulty in confidently assigning a diagnosis to this patient, as considerable overlap is becoming evident between Simpson‐Golabi‐Behmel syndrome and Perlman syndrome.

Histological changes in the left and right ventricle in hearts with Ebstein's malformation and tricuspid valvar dysplasia: A morphometric study of patients dying in the fetal and perinatal periods.

Both Ebsteins malformation and the related tricuspid valvar dysplasia are often associated with tricuspid regurgitation, and impaired right ventricular function may develop. Impaired function of the left ventricle in Ebsteins malformation has also been described. Interstitial fibrosis has been shown in the right and left ventricles of hearts with Ebsteins malformation from neonates, children, and adults. The objective of this study was to determine whether interstitial fibrosis seen in Ebsteins malformation is an intrinsic part of the congenital malformation or is acquired. From the fetal and perinatal periods, we compared 13 hearts with Ebsteins malformation (6 isolated and 7 with additional abnormalities) and 11 with tricuspid valvar dysplasia (3 isolated and 8 with additional abnormalities) with 16 controls. Three adult cases of isolated Ebsteins malformation in patients aged 17 to 20 years, were compared with 5 controls. The percentage of interstitial fibrous tissue and the thickness of the endocardium in the right and left ventricles were measured using histomorphometry. There were similar findings in Ebsteins malformation and tricuspid valvar dysplasia. Of 24 fetal and perinatal cases, 23 had normal interstitial fibrous tissue. Interstitial fibrosis was found in the right ventricle of only 1 perinatal heart with Ebsteins malformation and pulmonary stenosis. Of the 9 fetal cases, 4 had minimal right ventricular endocardial thickening (up to 10 μm). The left ventricular endocardium was normal in this group. Of the 6 perinatal cases with isolated Ebsteins malformation or tricuspid valvar dysplasia, 4 had right and 2 had left ventricular endocardial thickening (up to 345 μm). Of the 3 adult hearts with Ebsteins malformation, 2 had right ventricular endocardial thickening (47 and 225 μm) and 2 had right and 1 had left ventricular interstitial fibrosis. These results indicate that in both Ebsteins malformation and tricuspid valvar dysplasia the endocardial thickening develops in perinatal life, and in Ebsteins malformation the interstitial fibrosis develops in later life.

A Newly Recognized Autosomal Recessive Syndrome With Abnormal Vertebral Ossification, Rib Abnormalities, and Nephrogenic Rests

We describe three cases of a severe malformation syndrome in siblings of both sexes. The characteristic features observed were absent intrauterine ossification of an apparently normal cartilaginous spinal column; rib abnormalities, with unossified segments and posterior gaps; thoracic hypoplasia; and multiple intralobar nephrogenic rests in the kidneys. This syndrome can be identified in early pregnancy by ultrasound scans due to the lack of ossification of the thoraco‐lumbar spine and its association with increased nuchal translucency thickness. We suggest that this is a newly recognized autosomal recessive syndrome.

Mosaic trisomy 6 and maternal uniparental disomy 6 in a 23-week gestation fetus with atrioventricular septal defect

Trisomy 6 is seen in early miscarriages in association with an intact, empty amniotic sac or as a pseudomosaic in amniotic fluid cultures. We report the finding of mosaic trisomy 6 in a 23‐week‐gestation pregnancy terminated because of intrauterine death. The post‐mortem showed a well formed macerated male fetus with an atrioventricular septal defect and an exomphalos. By conventional cytogenetics, trisomy 6 was found in 12 out of 25 (48%) fibroblast colonies from fetal skin and 21 out of 32 (66%) colonies derived from amnion, while the remaining metaphases showed an apparently normal male karyotype. Molecular genetic studies on DNA from uncultured fetal skin and cord samples using polymorphic microsatellite repeat sequences showed no evidence of trisomy 6, but demonstrated that both chromosome 6 homologs were of maternal origin consistent with maternal uniparental disomy (UPD).

Carbonic anhydrase C as a marker antigen in the diagnosis of choroid plexus papillomas and other tumours: an immunoperoxidase study.

This study investigates the specificity of Carbonic Anhydrase C (CAC) as a marker antigen for choroid plexus papillomas and other primary and secondary brain tumours. Paraffin sections of normal brain, primary neuroepithelial tumours, and intracranial metastatic tumours were stained by the immunoperox-idase (PAP) technique for CAC, Glial Fibrillary Acidic Protein (GFAP) and S-100 protein. Normal choroid plexus contains CAC and S-100 but no GFAP whereas the six choroid plexus papillomas examined showed uniform staining for CAC and S-100 and patchy staining in the epithelium or stroma for GFAP. No other primary or metastatic tumour in the brain was found to contain CAC. Seven cases of colloid cyst from the third ventricle were totally negative for CAC, GFAP and S-100 protein. Oligodendrocytes in normal adult brain contain CAC in the cytoplasm and S-100 protein but they are negative for GFAP. In 5 cases of oligodendroglioma, no staining for CAC was seen in the tumour cells whereas many were stained for GFAP and S-100. Normal renal distal tubules, stomach epithelium and colon epithelium all contain CAC but carcinomas derived from these tissues do not. CAC was present in some tumour vessel endothelial cells. The results of this study suggest that (1) CAC is a reliable marker for choroid plexus papillomas and (2) colloid cysts may not be derived from neuroepithelial tissue.

Latent coeliac disease in childhood

We read with interest the paper by Matysiak-Budnik et al ( Gut 2007; 56 :1379–86) reporting the development of true latency or tolerance to gluten in adulthood. We would like to report a recent case of apparent serological and histological resolution of coeliac disease in childhood. In 2001 a 5-year-old girl presented with a 6-month history of recurrent abdominal pain. She had been previously well. There was no past history of food intolerance or family history of coeliac disease. She was found to be iron deficient on examination. Endomysial antibodies were strongly positive and a duodenal biopsy was entirely consistent with coeliac disease (fig 1). She was commenced on a gluten-free diet, which she adhered to for at least 6 months. …

Clinical outcomes of adjacent 1 segregation in a familial translocation t(8;18)(p21.3;p11.23).

We report a reciprocal translocation t(8;18)(p21.3;p11.23) in which both unbalanced products of adjacent 1 segregation were observed within a family. The proband was originally referred because of short stature and a webbed neck, but further investigations showed that she had mental retardation and a congenital heart defect, and had inherited an unbalanced form of the maternal translocation, 46, XX,der(8)t(8;18)mat. The probands sister spontaneously aborted an 11 week fetus with multiple major system malformations, which was found to have a 46,XY, der(18)t(8;18)mat karyotype. The phenotypic findings of the affected subjects are discussed.