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Biomedical subjects

J Roume

Publications and source records attributed to J Roume.

At least 19 recordsLinked to original sources
PubMed2006

Familial diseases revealed by a fetal anomaly.

OBJECTIVES: The recognition of a fetal anomaly can lead to the same diagnosis being made in one of the asymptomatic parents unaware of the problem. We analyzed cases in which the discovery of a fetal anomaly led to the discovery of a genetic familial disorder. METHODS: Families in which the recognition of a fetal anomaly led to the same diagnosis being made in one of the asymptomatic parents were included. RESULTS: Twenty couples were included in the study. The fetal anomalies were cleft lip and palate (4), cardiac anomalies (2), cerebral anomalies (1), bilateral club feet with polyhydramnios, akinesia or camptodactily (5), nuchal anomalies (2), micromelia (3), polydactyly (2), and limited elbow extension (1). Genetic counselling helped establish nine maternal diseases as follows: Steinert disease (3), spinal muscular atrophy (1), antecubital pterygium (1), DiGeorge (1), Wardenburg type II (1), Charge (1) and Greig syndromes (1). Eleven paternal diseases were discovered, which were Noonan-like syndrome (1), paternal cervical anomalies (1), Goldenhar syndrome (1), dominant autosomal arthrogryposis (1), osteogenesis imperfecta (3), tuberous sclerosis (1), dominant transposition of great vessels (1), Weyers acrofacial dysostosis (1), and autosomal dominant holoprosencephaly (1). Twelve couples continued with pregnancy and eight opted for termination of pregnancy. CONCLUSION: The fetus is central in giving the first insight into a familial disorder. It can reveal familial diseases undiscovered in the parent and help understand the mode of transmission of an anomaly, mainly the autosomal dominant diseases with variable expressions.

Abnormalities, Multiple↗
PubMed2004

Prenatal diagnosis of fetal skeletal dysplasias by combining two-dimensional and three-dimensional ultrasound and intrauterine three-dimensional helical computer tomography.

OBJECTIVE: To evaluate the contribution of new imaging techniques in the prenatal diagnosis of skeletal dysplasia. METHODS: Between May and October 2003, a prospective study was conducted in a single referral center. Three-dimensional ultrasound (3D-US) and three-dimensional helical computer tomography (3D-HCT) were performed after two-dimensional ultrasound (2D-US) in six cases of skeletal dysplasia. Diagnostic accuracy and detailed findings with each of the three techniques were compared with postnatal radiological findings. RESULTS: There were three cases of achondroplasia, two cases of osteogenesis imperfecta type II and one case of chondrodysplasia punctata. Termination of pregnancy was performed in five cases and one fetus with osteogenesis imperfecta type II was delivered at term by Cesarean section. 2D-US made the correct diagnosis in four cases. 3D-US and 3D-HCT achieved an accurate diagnosis in all six cases. 3D-HCT and 3D-US identified significantly more abnormalities than did 2D-US (3D-HCT: 94.3% (33/35); 3D-US: 77.1% (27/35); 2D-US: 51.4% (18/35); P < 0.01). The diagnosis was made between 27 and 36 weeks' gestation in all cases. The advantage of 3D-HCT over 3D-US was the possibility of imaging the entire fetus. CONCLUSION: 3D-US and 3D-HCT seem to be useful complementary methods to 2D-US, and may improve accuracy of the prenatal diagnosis of skeletal disorders. These new imaging technologies may have a role in the prenatal multidisciplinary approach to the diagnosis of skeletal dysplasias.

Chondrodysplasia Punctata↗
PubMed2003

Perinatal-lethal Gaucher disease.

Gaucher disease is a lysosomal storage disease caused by glucocerebrosidase deficiency. Although purely visceral in most cases, some Gaucher disease patients have neurological signs. Signs of Gaucher disease appear after a symptom-free period, except in rare cases with fetal onset. The description of such cases was based mainly on single reports and siblings. We report here a series of perinatal-lethal Gaucher disease cases highlighting the specificity of this phenotype. We retrospectively studied eight original cases of proven Gaucher disease with fetal onset. Non-immune hydrops fetalis was present in all cases but one, and associated with hepatosplenomegaly, ichthyosis, arthrogryposis, and facial dysmorphy. The similarities between our cases and 33 previously described cases allow us to better delineate the perinatal-lethal Gaucher disease phenotype. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurological involvement begins in the first week and leads to death within three months. Hepatosplenomegaly is a major sign, and associated with ichthyosis, arthrogryposis, and facial dysmorphy in some 35-43% of cases. Perinatal-lethal Gaucher disease is a specific entity defined by its particular course and signs that are absent in classical type 2 Gaucher disease. Our study provides clues to the diagnosis of this likely underdiagnosed condition, which must be biochemically confirmed in order to propose appropriate genetic counselling.

DNA Mutational Analysis↗
PubMed2002

Prenatal diagnosis of a 45,X male with a SRY-bearing chromosome 21.

Male phenotype associated with a 45,X karyotype is an infrequent finding. We present a case diagnosed prenatally on amniocentesis performed for maternal age. The male phenotype was associated with a translocation of a distal part of Yp including the pseudoautosomal SHOX gene and SRY gene on the short arm of a chromosome 21. By DNA analysis we could show that the X chromosome was of maternal origin and that the breakpoint was in interval 3 of the Y chromosome. Mechanisms and genetic counselling are discussed based on a review of published cases of 45,X and XX males.

Adult↗
PubMed2002

Fetal gender: antenatal discrepancy between phenotype and genotype.

Sexual discrepancy is reported in both 46,XY females and 46,XX males, and most diagnoses of sex reversal are made in the postpubertal period. We report three cases of sexual discrepancy, which were revealed by karyotyping following genetic amniocentesis, chorionic villus sampling and fetal blood sampling. The etiologies of 46,XX male, 45,X male and 46,XY female subjects are reviewed. When sexual discrepancy between fetal karyotype and ultrasonographic fetal phenotype is encountered, sample error and placental mosaicism should be excluded. A detailed fetal ultrasound examination should be performed to check for syndromic gender discrepancy. When repeat karyotyping is indicated, localization of the Sox related Y chromosome gene should be carried out.

Abnormalities, Multiple↗
PubMed2001

Prenatal diagnosis of hydrocephalus-stenosis of the aqueduct of Sylvius by ultrasound in the first trimester of pregnancy. Report of two cases.

Hydrocephalus-stenosis of the acqueduct of Sylvius sequence (HSAS) is characterized by hydrocephalus, macrocephaly, adducted thumbs, spasticity, agenesis of the corpus callosum and mental retardation. X-linked hydrocephalus is known to be due to mutations in the gene coding for the neural cell adhesion molecule L1 (L1-CAM) and diagnosis is made by identification of a mutation in the L1-CAM gene. Prenatal diagnosis of HSAS is usually suggested on ultrasound examination showing hydrocephalus in a male fetus associated with bilateral adducted thumbs. Mutation screening of the L1-CAM gene is indicated when neuropathological examination shows hypoplasia of the corticospinal tract associated with aqueductal stenosis. We report here two cases of HSAS diagnosed within the same family by ultrasound examination in the first trimester of pregnancy when bilateral adducted thumbs were the only early ultrasound marker.

Adult↗
PubMed2001

Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction.

Recent studies in transgenic mice have demonstrated that PTH-related protein (PTHrP), signaling through the type 1 PTH/PTHrP receptor (PTHR1), regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Recently, it has been shown that loss-of-function mutations in the PTHR1 gene result in a rare, lethal form of dwarfism known as Blomstrand chondrodysplasia. These patients suffer from severe defects in endochondral bone formation, but abnormalities in breast and tooth development have not been reported. To ascertain whether PTHrP signaling was important to human breast and tooth development, we studied two fetuses with Blomstrand chondrodysplasia. These fetuses lack nipples and breasts. Developing teeth were present, but they were severely impacted within the surrounding alveolar bone, leading to distortions in their architecture and orientation. Compatible with the involvement of PTHR1 and PTHrP in human breast and tooth morphogenesis, both were expressed within the developing breasts and teeth of normal human fetuses. Therefore, impairment of the PTHrP/PTHR1 signaling pathway in humans is associated with severe abnormalities in tooth and breast development. In addition to regulating human bone formation, this signaling pathway is also necessary for the normal development of the human breast and tooth.

Breast↗
PubMed1999

Splenogonadal fusion limb defect syndrome: report of five new cases and review.

Splenogonadal fusion (SGF) is a rare congenital malformation in which the spleen is abnormally connected to the gonad. SGF may occur as an isolated condition or may be associated with other malformations, especially with terminal limb defects in what is called splenogonadal fusion limb defect (SGFLD) syndrome. In this article, we report on 5 new cases of SGFLD and we review the 25 cases reported since 1889. Most cases reviewed here have a combination of severe limb and oro-mandibular defects, suggesting that SGFLD may be related to the broader group of Hanhart complex. In addition, several cases have limb malformations and facial anomalies, which suggest that SGFLD overlaps with both femur-fibula-ulna dysostosis and femoral-facial syndrome. The hypothesis of a vascular disruptive event, occurring between the 5th and the 7th weeks of gestation, could explain the limb defects, the mandibular hypoplasia, and the fusion of the spleen to the gonad observed in SGFLD. However, this heterogenous and polytopic condition could also be the consequence of a primary field defect. All the cases to date reported have been sporadic and the recurrence risk is probably low. However, a recent case of Roberts syndrome with SGF was reported that suggests careful examination of chromosomal status.

Abnormalities, Multiple↗
PubMed1998

Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia.

We report the absence of functional parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptors (PTH/PTHrP receptor) in Blomstrand chondrodysplasia, a genetic disorder characterized by advanced endochondral bone maturation. Analysis of PTH/PTHrP receptor genomic DNA from a patient with Blomstrand chondrodysplasia demonstrated that the patient was heterozygous for a point mutation (G--> A substitution at nucleotide 1176) inherited from the mother. Analysis of PTH/PTHrP receptor cDNA demonstrated that: (a) this point mutation caused the deletion of the first 11 amino acids of exon M5 (encoding the fifth transmembrane domain of the receptor), resulting from the use of a novel splice site created by the base substitution; (b) the mutant receptor was well expressed in COS-7 cells, but did not bind PTH or PTHrP, and failed to induce detectable stimulation of either cAMP or inositol phosphate production in response to these ligands; and (c) the paternal allele was not expressed. Thus, only the abnormal and nonfunctional PTH/PTHrP receptors encoded by the maternal allele were expressed by chondrocytes from this patient. In view of the known role played by the PTH/PTHrP receptor in bone and cartilage development, these results strongly support the conclusion that the absence of functional PTH/ PTHrP receptors is responsible for the skeletal abnormalities seen in Blomstrand chondrodysplasia, abnormalities that are the mirror image of those observed in Jansen's chondrodysplasia. These findings emphasize the importance of signaling through this receptor in human fetal skeletal development.

Base Sequence↗
PubMed1998

A gene for Meckel syndrome maps to chromosome 11q13.

Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown origin, characterized by (i) an occipital meningo-encephalocele with (ii) enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and (iii) postaxial polydactyly. A gene responsible for MKS in Finland has been mapped to chromosome 17q21-q24. Studying a subset of Middle Eastern and northern African MKS families, we have recently excluded the chromosome 17 region and have suggested a genetic heterogeneity. In the present study, we report on the mapping of a second MKS locus (MKS2) to chromosome 11q13, by homozygosity mapping in seven families that do not show linkage to chromosome 17q21-q24 (maximum LOD score 4.41 at recombination fraction .01). Most interestingly, the affected fetuses of southern Tunisian ancestry shared a particular haplotype at loci D11S911 and D11S906, suggesting that a founder effect is involved. Our observation gives support to the clinical and genetic heterogeneity of MKS.

Abnormalities, Multiple↗
PubMed1998

The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by alterations to the survival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that normal SMN protein expression undergoes a marked decay in the postnatal period compared with fetal development. Morphological and immunohistochemical analyses of the SMN protein in human fetal tissues showed a general distribution in the cytoplasm, except in muscle cells, where SMN protein was immunolocalized to large cytoplasmic dot-like structures and was tightly associated with membrane-free heavy sedimenting complexes. These cytoplasmic structures were similar in size to gem. The SMN protein was markedly deficient in tissues derived from type I SMA fetuses, including skeletal muscles and, as previously shown, spinal cord. While our data do not help decide whether SMA results from impaired SMN expression in spinal cord, skeletal muscle or both, they suggest a requirement for SMN protein during embryo-fetal development.

Animals↗
PubMed1997

Severe brain and limb defects with possible autosomal recessive inheritance: a series of six cases and review of the literature.

Six fetuses with normal chromosomes were found to have severe craniofacial, limb, and visceral malformations during the second trimester of pregnancy. Two of these fetuses were monozygotic twins while a third one had a healthy dizygotic twin brother. A case with familial recurrence was also observed. Autopsy and skeletal radiographs suggested several diagnoses such as neural tube defect with limb defects or XK aprosencephaly. The development of these severe conditions in monozygotic twins and familial recurrence emphasize the difficulties of genetic counseling in such situations. These cases may suggest autosomal recessive inheritance.

Abnormalities, Severe Teratoid↗
PubMed1997

Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further delineation.

We report on two sibs with a rare lethal chondrodysplasia born to a non-consanguineous couple. The hallmarks of this affection, also called Blomstrand chondrodysplasia, are short limbs, polyhydramnios, hydrops fetalis, facial anomalies, increased bone density, and a remarkable advance in skeletal maturation. We describe the radiologic and pathologic manifestations in these two cases. This recurrence affecting a male and a female fetus, born to the same couple, suggests autosomal recessive inheritance.

Adult↗
PubMed1997

Genetic heterogeneity of Meckel syndrome.

Meckel syndrome (MKS) is a lethal, autosomal recessive condition characterised by an occipital meningoencephalocele, enlarged kidneys with multicystic dysplasia, fibrotic changes of the liver in the portal area with ductal proliferation, and postaxial polydactyly. Recently, a MKS gene has been mapped to chromosome 17q21-q24 in Finnish families, with no evidence of locus heterogeneity in this population. Here, we report the exclusion of chromosome 17q21-q24 in eight typical MKS families of North African and Middle Eastern ancestry and provide evidence for genetic heterogeneity of this condition.

Abnormalities, Multiple↗
PubMed1997

[Neuropathological study of 134 fetuses in HIV infected mother].

A neuropathological study performed in 134 foetuses from HIV infected mothers, between 16 and 35 weeks of gestation, revealed two cases of hypoxic-ischemic brain damage, related to long labor and drug abuse. Immunostains against HIV proteins were negative in all cases. Nests of migrating cells in the cerebrum and cerebellar heterotopias were found in most cases and were considered to be common findings in fetal brain. Our study clearly showed the absence of cerebral HIV infection during early pregnancy and raises the question of the frequency of vertical transmission during HIV infection. However, the evaluation of cerebral changes in infants with HIV infection should take into consideration the features of the developing brain and the existence of other adverse factors that may interfere with its development during pregnancy.

Brain↗
PubMed1996

Lethal familial fetal akinesia sequence (FAS) with distinct neuropathological pattern: type III lissencephaly syndrome.

We report on a distinct pattern of primary central nervous system (CNS) degeneration affecting neuronal survival in the brain and spinal cord in 5 fetuses with fetal akinesia sequence (FAS). This neuropathological pattern is characteristic of a lethal entity that we propose calling type III lissencephaly syndrome. Parental consanguinity and the recurrence in sibs support a genetic cause. The mechanism of neuronal death is not yet understood; abnormal apoptosis and/or deficiency in neurotropic factors may be considered possible causes.

Abnormalities, Multiple↗