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Y Alembik

Publications and source records attributed to Y Alembik.

At least 19 recordsLinked to original sources
PubMed2006

Are the recommendations on the prevention of neural tube defects working?

Many studies showed that reduction by an estimated 80% or more of neural tube defects (NTD) by consumption of folic acid from before conception is achievable. The objectives of this study were to evaluate the effectiveness of recommendations on folic acid aimed at reducing the occurrence of NTD in our region. Cases of NTD were ascertained among liveborn infants, stillbirths, and terminations of pregnancy. Incidences and trends in rates of NTD before and after 1992 (the year of the first recommendations) and before and after 1995 (the year of local recommendations) were obtained. The results showed that the issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of NTD. The rates of NTD per 10,000 were before 1992 9.07, from 1993 to 1995 8.14, and after 1995 10.62, respectively. The incidence rate ratios (IRRs) were not different from 1.00. In conclusion new cases preventable by folic acid continue to accumulate. Recommendations alone did not influence trends in NTD in our country up to 11 years after the confirmation of the effectiveness of folic acid in clinical trials. New strategies are needed.

Anencephaly↗
PubMed2006

Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study.

Oral-facial-digital syndrome type 1 (OFD1) is characterised by an X linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, tooth, and distal abnormalities, polycystic kidney disease, and central nervous system malformations. Large interfamilial and intrafamilial clinical variability has been widely reported, and 18 distinct mutations have been previously reported within OFD1. A French and Belgian collaborative study collected 25 cases from 16 families. OFD1 was analysed using direct sequencing and phenotype-genotype correlation was performed using chi2 test. X inactivation studies were performed on blood lymphocytes. In 11 families, 11 novel mutations, including nine frameshift, one nonsense, and one missense mutation were identified, which spanned nine different exons. A combination of our results with previously reported cases showed that the majority of mutations (65.5%) was located in exons 3, 8, 9, 13, and 16. There was phenotype-genotype correlation between (a) polycystic kidney disease and splice mutations; (b) mental retardation and mutations located in exons 3, 8, 9, 13, and 16; and (c) tooth abnormalities and mutations located in coiled coil domains. Comparing the phenotype of the families with a pathogenic mutation to families with absence of OFD1 mutation, polycystic kidneys and short stature were significantly more frequent in the group with no OFD1 mutation, whereas lingual hamartomas were significantly more frequent in the group with OFD1 mutation. Finally, an X inactivation study showed non-random X inactivation in a third of the samples. Differential X inactivation between mothers and daughters in two families with high intrafamilial variability was of particular interest. Slight phenotype-genotype correlations were established, and X inactivation study showed that skewed X inactivation could be partially involved in the pathogenesis of intrafamilial clinical variability.

Adult↗
PubMed2005

Intrachromosomal triplication for the distal part of chromosome 15q.

We report the case of a boy whose karyotype at birth showed additional material on one chromosome 15. He underwent treatment for unilateral nephroblastoma at 6 years old. At 23 years old, he presented with body asymmetry, facial dysmorphism, arachnodactyly, severe scoliosis, and mental retardation. Molecular cytogenetic analyses of peripheral lymphocytes demonstrated a complex mosaic with three clones. A major cell lineage (68%) showed a chromosome 15 with additional material fused to its telomere long arm that was constituted by an inverted duplicated 15q24.3-qter segment. Therefore, the resulting add(15)(q) harbored an intrachromosomal triplication with the middle segment being inverted in orientation. A minor cell lineage (7%) showed an abnormal chromosome 3 resulting from a telomeric fusion between its short arm and an inverted duplicated 15q24.3-qter segment. The third cell lineage (25%) showed a normal 46,XY constitution. Finally, this resulted in tetrasomy for the distal 15q24.3-qter region in 75% of the patient's lymphocytes. To our knowledge, distal 15q tetrasomy is rare and only eight cases have been reported in the literature, all due to a supernumerary analphoid marker consisting of an inverted duplication. We report here the first observation of distal 15q tetrasomy associated with a 46 chromosomes constitution. We compare the phenotype of our patient to previous cases of distal tetrasomy 15q and discuss the mechanisms underlying this chromosomal rearrangement.

Abnormalities, Multiple↗
PubMed2004

Two cousins with partial trisomy 12q and monosomy 12p recombinants of a familial pericentric inversion of the chromosome 12.

Partial trisomy 12q and monosomy 12p lead to multiple malformation syndromes. Instead of trisomy 12q that has been reported as a clinically identifiable syndrome, monosomy 12p is characterized by a wide phenotypic spectrum. We report two cousins suffering from severe mental retardation, seizures, and dysmorphic features related to a trisomy 12q24.3-->qter and a monosomy 12p13-->pter resulting from a familial pericentric inversion of chromosome 12. In an attempt to improve the clinical delineation of these two syndromes, we compared our two patients with previous reports of these aneusomies. This review emphasizes the high frequency of familial translocations, including a breakpoint at 12q24 involved in trisomy 12q whereas monosomy 12p occurs most frequently de novo. Despite the poor specificity of the signs, this comparison allowed us to determine the clinical features present in more than 20% of patients with trisomy 12q or monosomy 12p. We particularly emphasize some consistent leading features of monosomy 12p, including microcephaly, dental, cardio-vascular, extremity, and sensorial abnormalities, initially not reported as recurrent in this syndrome.

Child, Preschool↗
PubMed2004

Familial cylindromatosis.

Familial cylindromatosis: we report a daughter with turban tumor and her mother with cylindromatosis. The dermal eccrine cylindroma arose as small, solitary lesions on the head of the mother when she was 28 years old. The following years other tumors became apparent. She was operated on several times. The first lesions appeared on the frontal part of the scalp of the daughter when she was 23 years old. Other tumors grew on the scalp. Histopathological examination of the excised tumors showed the same lesions in both the mother and the daughter: dermal eccrine cylindromata. Family history showed that the daughter's maternal aunt had a few tumors. Dermal eccrine cylindroma should be differentiated from malignant syndromes such as basal naevoid carcinoma or metastases and from neurofibromata. The gene of familial cylindromatosis was localised to chromosome 16q12-q13 and it was proposed that this gene is a tumor supressor gene.

Adult↗
PubMed2004

Brachydactyly type E in two sibs with increased bone density and mental retardation. A new autosomal recessive syndrome?

Brachydactyly type E in two sibs with increased bone density and mental retardation. A new autosomal recessive syndrome?: We report on two sibs, a boy and a girl, with syndromic brachydactyly type E. Parents were first cousins. Facial dysmorphia was characterized by a flat occiput, a large forehead, hypertelorism, a long triangular nose, an everted lower lip, downslanting palpebral fissures and strabismus. They had marked shortening of the third, fourth and fifth fingers and of the third, fourth, and fifth toes. IQ was 16 in the boy, 63 in the girl. In both sibs ophtalmologic examination showed strabismus, absence of cataract and normal fundus and radiological findings disclosed increased bone density involving the skull, the vertebrae and the corticalis of the long bones. Neither ectopic calcifications, nor exostosic, nor osteomalacia, and nor osteotis fibrosa cystica were present. Investigations revealed that plasma calcium, phosphate, vitamine D, parathyroid hormone (PTH), response to exogenous PTH, and Gs activity were normal as well as renal and thyroid function. Molecular genetic studies failed to identify mutations in the GNAS 1 gene, in the PTH receptor gene and in the HOX D13 gene. Analysis of 2q showed that there was no deletion 2q37. Other known syndromes with brachydactyly type E and mental retardation were excluded. In conclusion we suggest that these two sibs with a combination of brachydactyly, mental retardation and increased bone density have a specific autosomal recessive syndrome.

Adult↗
PubMed2002

An unusual human mosaic for skin pigmentation.

Patterned pigmentary disturbances are seen in a large variety of human genetic disorders. Cytogenetic studies have provided evidence that such skin lesions often reflect chromosomal mosaicism. In addition to the well-known pattern of Blaschko's lines a classification of several distinct types was proposed by Happle. This report add the case of a boy with an unusual mosaic-like distribution of skin pigmentation and a further chromosomal anomaly which has not been described in pigmentary mosaicism previously. The proband was born after an uneventful pregnancy and delivery. Developmental milestones were delayed. A generalised hirsutism was noted with a facial dysmorphia: coarse facies. short philtrum, synophris, and large low set years. Hyperpigmentation followed a checkerboard pattern: alternating squares of pigmentary anomalies with a sharp midline separation. Cytogenetic findings Included a normal karyotype (peripheral blood) and a mosaicism 12q;14q translocation (70% of fibroblasts). The present case stresses the importance of careful chromosomal analysis of different tissues in patients with pigmentary anomalies.

Child, Preschool↗
PubMed2002

Severe hypophosphatasia due to mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene.

Hypophosphatasia is a rare autosomal recessive inborn error of metabolism characterized by a defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation in a patient affected by infantile hypophosphatasia. This boy was the first child of non affected, non related parents. At 1 month of age he presented with palsy of the left upper limb with hypotonia. Length was - 2SD. The anterior fontanel was large. There was a markedly decreased ossification of all bones. All limbs were shortened. Ultrasonographic examination of the kidneys showed nephrocalcinosis. Level of alkaline phosphatases was decreased in the child as well as in the parents. Bone density was decreased. At 2 years of age development was delayed. Weight was - 3,5 SD and OFC - 3SD. The child had craniosynostosis. Molecular studies showed 2 missense mutations, both in exon 6 of the TNSALP gene.

Alkaline Phosphatase↗
PubMed2001

Severe hypernatremic dehydration in an infant with Netherton syndrome.

Netherthon syndrome is a rare autosomal recessive disease characterized by ichthyosis, the characteristic hair abnormality trichorrhexis invaginata and atopic manifestations. We report a female child with the severe hypernatremic dehydration form of the Netherton syndrome born as the first child of consanguineous parents. Ichthyosis was present at birth. She was admitted to the intensive care unit at the age of 4 days with important loss of weight and dehydration. Severe hypernatremia and convulsions occurred. Despite intensive care the baby died at the age of 11 days. The diagnosis of Netherton syndrome was confirmed by the finding of the pathognomonic hair shaft anomaly trichorrhexis invaginata (bamboo hair) and premature lamellar body secretion and foci of electron-dense material in the intercellular spaces of stratum corneum as relatively specific markers for Netherton syndrome. Netherton syndrome is characterized by a large variability in phenotypic expression. The major neonatal complication is the hypernatremic dehydration, which can be fatal as in this patient or complicated by neurologic signs (intracranial hemorrhage) and secondary sequellae. Molecular studies revealed a mutation in SPINK 5, encoding a serine protease inhibitor. Prenatal diagnosis was performed in the second pregnancy and showed that the fetus was equally affected.

Carrier Proteins↗
PubMed2000

Associated malformations in cases with oral clefts.

OBJECTIVE: Infants with oral clefts (OCs) often have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. METHOD: The prevalences at birth of associated malformations in infants with OCs were collected between 1979 and 1996 on all infants born in the area covered by the registry of congenital anomalies of Northeastern France in 238,942 consecutive births. RESULTS: Of the 460 cleft infants born during this period, 36.7% had associated malformations. Associated malformations were more frequent in infants who had cleft palate (46.7%) than in infants with cleft lip and palate (36.8%) or infants with isolated cleft lip (13.6%). Malformations in the central nervous system and in the skeletal system were the most common other anomalies, followed by malformations in the urogenital and cardiovascular systems. Weight, length, and head circumference of children with OCs and multiple associated malformations were lower than in controls, as was the weight of the placenta. Prenatal diagnosis was rarely done by fetal ultrasonographic examination in isolated clefts. However, even in multiple associated malformations, prenatal diagnosis by fetal ultrasonographic examination had a low sensitivity, 31.6%. CONCLUSION: The overall prevalence of malformations, which was one in more than three infants, emphasizes the need for a thorough investigation of infants with clefts. A routine screening for other malformations especially skeletal, central nervous system, and cardiac defects may need to be considered in infants with clefts, and genetic counseling seems warranted in most of these complicated cases.

Abnormalities, Multiple↗
PubMed1999

Study of 290 cases of polyhydramnios and congenital malformations in a series of 225,669 consecutive births.

OBJECTIVES: To provide data on polyhydramnios associated with congenital anomalies in 225,669 consecutive pregnancies. MATERIAL AND METHODS: The information in this study came from births of known outcome recorded in our registry of congenital malformations. Routine ultrasonographic examination was performed. Polyhydramnios was diagnosed ultrasonographically. A case-control study allowed the examination of genetic and environmental causal factors of polyhydramnios associated with congenital malformations. RESULTS: The prevalence of this association was 1.28/1,000 (290 cases). Polyhydramnios associated with congenital malformations was diagnosed prenatally in 44.5% of the cases, 10.3% of the infants were stillborn. Forty-one percent of the cases had more than one malformation, 14.5% had a chromosomal aberration, and 20.0% had multiple malformations that do not constitute a syndrome. The more frequent malformations associated with polyhydramnios were cardiac, digestive, central nervous system, musculoskeletal, and urinary. There was increased parental consanguinity. The incidence of polyhydramnios and congenital anomalies among first-degree relatives was 4.1% and first-degree relatives had more malformations than controls (6.2 vs. 3.2%, p < 0.05). Threatened abortions and diabetes mellitus were significantly more frequent among mothers of children with congenital malformations associated with polyhydramnios than among controls. CONCLUSIONS: Our study demonstrated that careful fetal examination has to be performed when polyhydramnios is diagnosed as congenital malformations are often associated with polyhydramnios. We recommend the use of fetal chromosome analysis and careful ultrasonographic examination in every pregnancy complicated by polyhydramnios.

Journal Article↗
PubMed1999

Congenital anomalies associated with congenital hypothyroidism.

The French national neonatal screening program for congenital hypothyroidism (CH) was initiated in 1978. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with congenital hypothyroidism (CH) and to compare it with the Northeastern France Birth Defect Monitoring System data from 1979 to 1996. Among 129 CH infants on whom adequate data were available, 20 infants (15.5%) had associated congenital anomalies. Eight out of 76 infants with persistent CH had ETAs (10.5%) whereas 12 out of 53 children with transient hypothyroidism had ETAs (22.6%, p < 0.05). Some additional anomalies were considerably more common than in the general population. Nine infants had congenital cardiac anomalies (6.9%). This rises the question if teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETAs.

Congenital Abnormalities↗
PubMed1999

Growth curves of children with Down syndrome.

Growth curves of 105 children with Down syndrome (50 boys and 55 girls) were established. At birth height, weight and head circumference of Down syndrome children were lower than these parameters in controls. This delay remained stable until puberty. For weight there was no clear-cut pubertal growth spurt. For stature, the prepubertal growth spurt occurred earlier (at the age of 11 years in boys and 9 1/2 years in girls) than in controls but was less marked. As a result, Down syndrome patients had a short stature with a quite normal weight. These reference curves, available since prenatal diagnosis of Down syndrome is performed routinely, are helpful for monitoring normal and abnormal development in Down syndrome patients.

Adolescent↗
PubMed1999

Parental consanguinity as a cause for increased incidence of births defects in a study of 238,942 consecutive births.

The risk for birth defects in the offspring of first-cousin matings has been estimated to increase sharply compared to non consanguineous marriages. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies we tried to answer to this question. In the population studied in North-Eastern France a consanguineous mating was known in 1.21% of the cases with congenital anomalies, vs. 0.27% in controls, (p < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 89 malformed children, 51 were seen in first-cousins mating (10.3 times more frequent than in offspring of non consanguineous couples), 17 in second-cousins marriages and 18 in more distant relatives mating. Three were uncle-niece marriage. Excluding known mendelian conditions these numbers were 73, 36, 17 and 17 respectively and the corresponding relative risk were 3.68, 3.01, 3.41 and 4.89 respectively. Therefore there is a negative dose-response effect between level of inbreeding and risk of congenital malformations. Consanguineous mothers were more often pregnant than non consanguineous mothers (p < 0.01) and they had more stillbirths than non consanguineous mothers. These results show that consanguinity is still a factor of birth defects and they must be taken into account for genetic counseling of inbred marriages, in developed countries.

Congenital Abnormalities↗
PubMed1999

Familial coarctation of the aorta in three generations.

Four members in three generations of a family were affected by a coarctation of the aorta (CoA) which was mild or severe, either isolated or in association with other cardiac defects. This family suggests that a rare form of CoA could be the result of an autosomal dominant mutation with incomplete penetrance and variable expressivity rather than polygenic inheritance.

Aortic Coarctation↗