Diagnostic yield of chromosomal microarray analysis in fetuses with isolated increased nuchal translucency: a French multicenter study.

OBJECTIVE: To determine the frequency and nature of copy number variants (CNVs) identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses with isolated increased nuchal translucency thickness (NT) ≥ 3.5 mm. METHODS: This was a retrospective, multicenter study, including 11 French hospitals, of data from the period between April 2012 and December 2015. In total, 720 fetuses were analyzed by rapid aneuploidy test and the fetuses identified as euploid underwent CMA. CNVs detected were evaluated for clinical significance and classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs not related to the phenotype (i.e. incidental findings). RESULTS: In 121 (16.8%) fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53 (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic, including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599 (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%) were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the reason for referral diagnosis (i.e. an incidental finding) and the remaining 21 were benign CNVs, without clinical consequence. Interestingly, we identified five genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with congenital heart defects. CONCLUSION: Our study demonstrates the benefit of CMA in the etiological diagnosis of fetuses with isolated increased NT. It is worth noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.

The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression.

Inverted duplication with deletion: first interstitial case suggesting a novel undescribed mechanism of formation.

Inverted duplications with terminal deletions are a well-defined family of complex rearrangements already observed for most of chromosome extremities. Several mechanisms have been suggested which could lead to their occurrence, either through non-homologous end joining, non-allelic homologous recombination, or more recently through an intrastrand fold-back mechanism. We describe here a patient with intellectual disability and pharmacoresistant epilepsy, for which array CGH analysis showed the first interstitial case of inverted duplication with deletion on chromosome 1p. Furthermore, SNP array analysis revealed an associated segmental isodisomy for the distal part of 1p, which led us to consider a replicative mechanism to explain this abnormality. This observation extends the range of this once telomeric rearrangement.

Pregnancy outcomes of prenatally diagnosed Turner syndrome: a French multicenter retrospective study including a series of 975 cases.

OBJECTIVES: The objectives of this study were to report pregnancy outcomes after prenatal diagnosis of Turner syndrome (TS) and to compare and assess termination of pregnancy rates during two periods. The intervals selected were before and after 1997 when multidisciplinary centers for prenatal diagnosis (MCPDs) were established in France. METHODS: A database of 975 cases of TS diagnosed between 1980 and 2012 was created from 21 French cytogenetics laboratories. For each case, the karyotype indication, maternal age, year of prenatal testing, sampling procedure, karyotype, associated ultrasound findings, and outcomes were recorded. RESULTS: Karyotypes were mainly performed because of abnormal sonographic findings (84%). Before 1997, there were no changes in the rate of termination (90%) of affected fetuses. After 1997, the rate fell to 80%. This decrease was mainly observed in cases of mosaicism, incidental diagnosis, and in later gestations. US abnormalities were more likely to be associated with a full 45,X karyotype. CONCLUSION: There was an evolution in the way genetic counseling was performed following prenatal diagnosis of Turner syndrome that coincided with the opening of MCPDs in France. This resulted in a decrease in the rate of termination of affected fetuses.

A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes.

OBJECTIVE: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. METHODS: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. RESULTS: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate. CONCLUSION: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.

A novel homozygous MMP2 mutation in a family with Winchester syndrome.

The 2001 International Classification of Constitutional Disorders of Bone has included in the group of multicentric hands and feet osteolysis syndromes three autosomal recessive inherited disorders: Winchester, Torg and nodulosis-arthropathy-osteolysis (NAO) syndromes. Nosographic delineations of these rare syndromes are difficult to define, and there is no consensus. In 2001, two mutations in the matrix metalloproteinase 2 gene (MMP2) have been identified in two families with a NAO phenotype. In a recent study, a homozygous MMP2 mutation has also been identified in a patient presenting with Winchester syndrome. We report the clinical evolution of two sisters with a Winchester phenotype. Clinical review over 23 years provides information on the general evolution of osteolysis and points to an intrafamilial variation with clinical and radiological changes during the patients' life. In both sisters, we identified a new homozygous mutation in the catalytic domain of the MMP2 gene. Our study results are consistent with the involvement of MMP2 in Winchester syndrome and with the hypothesis that Winchester and NAO syndromes are allelic disorders that form a continuous clinical spectrum. At last, our observation emphasizes the interest of molecular analysis in genetic counselling of this consanguineous family.

Prevalence of cholelithiasis: results of an epidemiologic investigation in Vidauban, southeast France. General Practitioner's Group of Vidauban.

Cholelithiasis leads to 80,000 cholecystectomies being performed every year in France, but its prevalence is still unknown. The aim of this study was to assess the prevalence and risk factors of cholelithiasis in a random population of 1027 women and 727 men over the age of 30 in a small town in the southeast of France. Detailed clinical history, dietary investigation, and gallbladder ultrasound were collected for each subject and assessed by univariate analysis. A regression model was used in the multivariate analysis to detect the relative risk of cholelithiasis. Cholelithiasis was found in 130 individuals (global prevalence 13.9%). The relative risk for lithiasis was higher in women compared to men (1.89). Age (P<0.0001) and body mass index (BMI) >25 (P = 0.013) were also significant risk factors. Neither pregnancy nor oral contraceptive use proved to be risk factors. Typical biliary colic pain was the only symptom significantly associated with cholelithiasis (P<0.0001). These results show that the prevalence of gallstones in France is similar to that in Denmark and Italy.

[Radiologic aspects of the complications of duodenal diverticula]. / Aspects radiologiques des complications des diverticules duodénaux.

The duodenum is the second most common site, after the colon, for intestinal diverticulae. This condition is most often asymptomatic and is usually an accidental finding. Complications, with variable clinical presentations, may occur in up to 5% of such individuals. We report a retrospective analysis of 5 patients who presented with complicated duodenal diverticular disease. The complications, either isolated or multiple, consisted of bezoar formation (n = 2), diverticulitis (n = 2), extrinsic compression of the common bile duct (n = 3), perforation (n = 1), choledocholithiasis (n = 1), and an abnormality of the bilio-pancreatic ductal convergence (n = 1). The radiological aspects, in particular, the magnetic resonance imaging (MRI) features are reviewed. These are, to our knowledge, the first descriptions of MRI and magnetic resonance cholangiopancreatographic (MRCP) findings in complicated duodenal diverticular disease. MRI facilitates precise delineation of the complicated duodenal diverticulum while MRCP allows assessment of the effects on the biliary and pancreatic ducts.

[Ultrasonographic and MRI aspects of cystic duodenal dystrophy with aberrant pancreatic tissue]. / Aspects en echographie et en IRM d'une dystrophie kystique duodenale sur pancreas aberrant.

US and MR features (including MR cholangiopancreatography) of a cystic formation in a duodenal heterotopic pancreas are reported. To our knowledge, MR cholangiopancreatography of this uncommon condition has not been previously described. Imaging showed multiple cysts within a thickened duodenal wall. This thickness of the duodenal wall was related to a heterotopic pancreas with chronic pancreatitis.

Hepatic multi-nodular focal fatty metamorphosis in acquired porphyria cutanea tarda. Sonographic, CT, and MRI features.

The authors report the sonographic, computed tomography (CT), and magnetic resonance imaging (MRI) findings in a patient with acquired porphyria cutanea tarda and hepatic multi-nodular focal fatty metamorphosis. There has only been one previous description of an association between these two conditions. The diagnosis was confirmed by histological analysis of a liver biopsy specimen. Symptomatology related to the hepatic abnormality may be due to an inflammatory reaction induced by the presence of uroporphyrin crystals in the liver. Each of the radiological techniques demonstrated unusual hepatic abnormalities and, in particular, MRI showed poorly defined areas in the liver which, on T2-weighted sequences, exhibited a hypersignal with fat saturation. Treatment of porphyria cutanea tarda led to clinical remission and resolution of radiological abnormalities.

[Post-traumatic hypopituitarism after skull injury: apropos of 3 cases]. / Hypopituitarisme post-traumatisme crânien: à propos de trois cas.

BACKGROUND: Hypopituitarism is a rare but well-known complication of cranial trauma. In the absence of overt diabetes insipidus, its recognition is difficult as the onset of clinical symptoms can be very progressive, up to several years. CASE REPORTS: Three children, aged 8, 9 and 2 years, respectively, were admitted after a cranial trauma. Manifestations of diabetes insipidus occurred a few days later in two patients; one of them developed secondary growth hormone deficiency, hypothyroidism and hypogonadism, only evidenced at the age of 14 years. The third patient also developed manifestations of hypothalamic and/or pituitary hormone deficiencies without diabetes insipidus at the age of 12 years-6 months. MRI showed complete severance of the pituitary stalk in two patients and absence of posterior pituitary signal in one of the two patients with diabetes insipidus. CONCLUSION: Growth disorders and/or hypogonadism may occur many years after a trauma that may have been forgetten. Search for such an etiology and dynamic MRI are necessary in identifying heterogenous hypophyseal lesions.

[Image data bases and multimedia works on server and CD-ROM in medical imaging. A French experience]. / Iconothèques et ouvrages multimédia sur serveur et CD-ROM en imagerie médicale. Expérience Française.

The CD-ROM technology allows the production of multimedia works which costs far less than books do. The creation of Internet and the servers World Wide Web has the advantage of distributing those works world wide, without the difficulties and the delays related to books and magazines distribution. The Teachers' Council of Radiology of France (CERF) and the French Society of Radiology (SFR) have opted to use these new media and these information highways to spread a part of their radiology teaching work. Iconocerf is a software program which allows to create, store, read and to exchange digitized radiological cases. It's available free of charge, within the CERF and SFR. The CD-ROMs Iconocerf-Medimag contain 3,500 radiological files with 15,000 images, previously on the videodisc Medimag. The Server of the French Radiology is a W3 server which includes: the CERF directory, a guide for the teachers, the research workers and the students in Radiology and Medical Imaging. It also contains the teaching works on Radiology, and some Iconocerf clinical cases translated onto HTML. The aim of this project is to create an evaluation system for radiology. By using key words, this system allows to consult: radiological clinical cases, located on the server or on CD-ROMs; reference texts; and to have access to the experts' addresses to be able to send them eventually a difficult case through electronic mail.

Nephrocalcinosis and prematurity: importance of urate and oxalate excretion.

Nephrocalcinosis was described in preterm infants by several authors who tried to determine its association with hypercalciuria and furosemide therapy. We evaluated these potential mechanisms along with other lithogenic factors not previously studied in 10 premature babies. Hypercalciuria was an inconsistent finding like in other reports; elevated uric acid excretion and hyperoxaluria were observed in 5 and 6 cases, respectively. The aminocid excretion was normal in all infants. Our data suggest that in addition to hypercalciuria, other lithogenic factors may play a role in the pathophysiology of nephrocalcinosis of premature infants.

[Sertoli-Leydig tumors in children. 2 case reports]. / Tumeurs de Sertoli-Leydig de l'enfant. A propos de deux observations.

Sertoli-Leydig tumors stem from the mesenchyma and sexual cords of the embryonic gonad. Two cases are reported. One manifested as symptoms of virilization in a 12 year old girl. The other patient developed adnexal torsion at the age of five years. Pelvic ultrasonography visualized the tumor in both cases. Increased production of ovarian androgens suggested the diagnosis in the first case. Histological studies disclosed intermediate differentiation in the first case and tubular differentiation in the second. These tumors usually exhibit low-grade malignancy and unilateral salpingo-oophorectomy ensures recovery in most instances.

[Severe colectasy in rheumatoid purpura. Probable role of water soluble contrast products]. / Colectasie grave au cours d'un purpura rhumatoïde. Rôle probable des produits de contraste hydrosolubles.

BACKGROUND: About 60-70% of cases of anaphylactoid purpura suffer from abdominal colic, which may be quite severe. Because severe abdominal pain may be difficult to differentiate from a surgical abdomen, repeated examination and radiological studies are often necessary. CASE REPORT: A 4 year 7 month-old girl suffered from abdominal pain, vomiting and the skin rash characteristic of anaphylactoid purpura. Because of worsening of the abdominal manifestations, a Gastrografin enema was given. The result was normal but 48 hours later, the child suffered from acute abdominal colics plus symptoms of shock. X-ray examination revealed a large distension of colon and persistence of the contrast material. Exploratory laparotomy failed to find any perforation or necrosis. The colon was drained and the child was given parenteral nutrition and antibiotics. Blood culture showed Klebsiella pneumoniae. An upper gastrointestinal roentgenogram using meglumine ioxitalamate was performed 19 days later because of recurrence of the abdominal pain. This showed a submucosal hemorrhage in the first small bowel loop. Increased abdominal distension occurred 3 days later and the results of X-rays were similar to those seen the Gastrografin enema. A second enema using meglumine ioxitalamate was performed 3 days later. It showed sigmoid constriction but a second laparotomy failed to confirm this obstruction. The child died a few hours later despite ileostomy and antibiotics. CONCLUSIONS: The severe colectasy seen in this case of anaphylactoid purpura indicates that caution is required in performing enemas in acute digestive complications of this disease. Such X-ray studies should not be repeated and all water-soluble contrast material should be voided as soon as possible.

[Pseudo-tumoral circumscribed myositis ossificans of the thoracic wall. Contribution of ultrasonography, x-ray computed tomography and MRI]. / Myosite ossifiante circonscrite pseudo-tumorale de la paroi thoracique. Apport respectif de l'échographie, de la tomodensitométrie et de l'IRM.

The authors report the main clinical and radiographic aspects of a circumscribed myositis ossificans in a 5 year old child located in the thoracic wall, near the sternum, stimulating a malignant tumor. CT scan was more contributive than MRI, both for diagnosis and survey, because it shows better the progressive peripheral calcification typical of the lesion.