1/28. Small for gestational age infant in association with maternal prothrombin gene variant (nt 20210A).Most of disproportionate infants born small for gestational age (SGA) have an history of placental dysfunction with no explained cause. We report a case of an unexplained SGA infant with placental infarctions and thrombosis. Maternal thrombophilic disorder tests revealed that the patient was heterozygous for the A20210 prothrombin gene variant a newly identified thrombotic risk factor. It may be suggest that prothrombin gene variant, as factor v Leiden, could be a genetic risk factor for placental insufficiency.- - - - - - - - - - ranking = 1keywords = placental insufficiency, insufficiency (Clic here for more details about this article) |
2/28. IMAGe, a new clinical association of intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies.We report three boys with adrenal hypoplasia congenita (AHC) and additional findings that represent a new syndrome, IMAGe: Intrauterine growth retardation, Metaphyseal dysplasia, AHC, and Genital anomalies. Each presented shortly after birth with growth retardation and severe adrenal insufficiency. Each of the three patients had mild dysmorphic features, bilateral cryptorchidism, a small penis, and hypogonadotropic hypogonadism. Skeletal surveys revealed metaphyseal dysplasia in all three and epiphyseal dysplasia in two. The patients had documented or suspected hypercalciuria and/or hypercalcemia, resulting in nephrocalcinosis in one and in prenatal liver and spleen calcifications in another. AHC presents most often either as an isolated abnormality, caused by mutations in the DAX1 gene, or as part of an Xp21 contiguous gene syndrome, caused by a deletion of the Duchenne muscular dystrophy, glycerol kinase, and DAX1 genes. All three patients with the IMAGe association had normal creatine kinase levels and no evidence of glycerol kinase deficiency. sequence analysis of dna from these patients revealed no mutation in the DAX1- or steroidogenic factor-1-coding sequences, nor was a deletion of DAX1 detected. Identification of the molecular basis of the IMAGe association will give new insight into the pathogenesis of this syndromic relationship involving bone, adrenal cortical, and pituitary development.- - - - - - - - - - ranking = 4.1250786445552E-5keywords = insufficiency (Clic here for more details about this article) |
3/28. Johanson-Blizzard syndrome. a new case with autopsy findings.Here we present a new case of Johanson-Blizzard Syndrome. Clinical features consistent with the diagnosis of Johanson-Blizzard Syndrome in a term neonate are described: intra-uterine growth retardation, aplasia of the nasal alae, midline scalp defect, total situs inversus, imperforate anus, malrotation of the small intestine, pancreatic insufficiency, deafness, and lethal congenital heart defects with dextrocardia. These features were confirmed by findings at autopsy. parents were consanguineous. We compare these clinical features and findings at autopsy with previous cases reported in the literature.- - - - - - - - - - ranking = 4.1250786445552E-5keywords = insufficiency (Clic here for more details about this article) |
4/28. Restrictive dermopathy: a case report and a critical review of all hypotheses of its origin.Restrictive dermopathy (RD) is a rare, fatal, autosomal recessive genodermatosis in which tautness of a translucent thin skin is the major clinical observation. This causes an intrauterine fetal akinesia deformation sequence (FADS) resulting in polyhydramnios, reduced fetal movements at around 31 weeks gestation, dysmorphic facies, arthrogryposis, and early neonatal death because of respiratory insufficiency. The characteristic histologic abnormalities of the skin are located in a thin dermis, consisting of compactly arranged collagen fibers, scant elastic fibers, and poorly developed skin appendages. The epidermal rete ridges are flattened and the dermal-hypodermal border is remarkably straight. The etiology of these changes remains unclear. We tested several existing hypotheses and could not confirm them. These included fibroblast dysfunction, abnormal keratin composition, desmosomal changes, and increased proinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6]. We conclude that RD is a relatively easy clinical and pathologic diagnosis, but that the pathogenesis of the disease is not clarified.- - - - - - - - - - ranking = 4.1250786445552E-5keywords = insufficiency (Clic here for more details about this article) |
5/28. IGF-related proteins at birth in a case of antenatally diagnosed silver-russell syndrome.We report here a case with severe intrauterine growth restriction from the first trimester and clinical features of silver-russell syndrome including microcephaly, low-set ear, atrial septum defect, ventricular septum defect, diaphragmatic relaxation, and rocker bottom feet. silver-russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. We measured both the maternal and cord blood levels of GH, IGF-I, and IGF-binding protein and performed an immunohistochemical study of IGF-IR in the placenta to investigate whether these IGF-related proteins were affected in this patient. The hormonal level of these proteins did not significantly differ from normal neonates, and immunohistochemical analysis suggested IGF-IR protein levels in the placenta were comparable to normal term neonates. These results support the hypothesis that growth insufficiency could occur in patients with monosomy of the distal long arm of chromosome 15 and suggest a critical threshold for IGF-related fetal growth in early pregnancy.- - - - - - - - - - ranking = 4.1250786445552E-5keywords = insufficiency (Clic here for more details about this article) |
6/28. IMAGe association: additional clinical features and evidence for recessive autosomal inheritance.Congenital adrenal hypoplasia (CAH) normally occurs in the neonatal period, with patients presenting with more or less severe salt-wasting syndrome. X-linked CAH has been associated with mutations in the DAX-1 gene, and boys have also been shown to have hypogonadotrophic hypogonadism. Recently, in three unrelated boys, CAH was associated with intrauterine growth retardation (IUGR), metaphyseal dysplasia and genital abnormalities, defining a new association called IMAGe. We now report four additional patients with this association, including the first living female. The four patients belong to two unrelated families (one brother and one sister from each family). These patients have the main clinical characteristics of IMAGe association: IUGR, facial dysmorphy (frontal bossing, broad nasal bridge, low-set ears), short limbs due to metaphyseal dysplasia, and adrenal insufficiency. As these patients are older than the initial three patients, we can also describe additional features: short adult height, normal puberty in boys as well as in the living girl. The boys have hypospadias associated with micropenis. The living girl came to clinical attention at the age of 5 years as a result of a familial survey, and careful questioning revealed that she had been suffering from mild adrenal insufficiency since early childhood. At least one boy has congenital hypotonia due to muscular dystrophy. In conclusion, these four new cases display familial transmission, strongly suggesting Mendelian autosomal recessive inheritance. adrenal insufficiency may be mild. Hypotonia, described in all the patients, might be related to paucisymptomatic muscular dystrophy, as this condition is clearly heterogeneous varying with regard to severity, associated manifestations and outcome. If this symptom is part of the syndrome, which we cannot assume, it could help to localize the candidate gene.- - - - - - - - - - ranking = 0.00012375235933666keywords = insufficiency (Clic here for more details about this article) |
7/28. Characterization of genomic variants in CSH1 and GH2, two candidate genes for silver-russell syndrome in 17q24-q25.silver-russell syndrome (SRS) is a syndrome of severe pre- and postnatal growth retardation and typical dysmorphic features. Rare chromosomal aberrations have been reported in SRS; among these are two balanced translocations involving 17q24-q25. Recently, we described a patient with a paternally inherited heterozygous deletion of the chorionic somatomammotropin hormone 1 (CSH1) gene. The CSH1 gene is member of the growth hormone (GH) gene cluster on 17q, which consists of two growth hormone genes and three CSH genes. Genomic alterations in the GH cluster are well known, causing different phenotypes depending on the size of the deletion and the genes involved. By screening 63 SRS cases with marker D17S254, we have detected 2 further patients with a heterozygous deletion in the GH cluster. Quantitative analysis using restriction assays confirmed these findings. Additionally, in a cohort of 17 patients with isolated intrauterine and postnatal growth retardation, we detected a further patient to be carrier of a CSH1 deletion. Screening of 141 unrelated controls revealed hemizygosity in one person for which data on growth were not available. We additionally analyzed our cohort of SRS patients for mutations in CSH1 and its 3' neighbour GH2. However, analyses failed to reveal any pathogenic mutation. While the central role of GH1 in human growth is well established, the physiological roles of CSH1 and other components of the cluster are unclear. The increased prevalence of hemizygosity of CSH1 in our population in comparison to controls indicates a role for CSH1 haploinsufficiency in the etiology of growth retardation. Investigation of CSH1 deletions in further SRS and growth retarded patients will enable us to establish under which circumstances haploinsufficiency of CSH1 is likely to result in clinical changes.- - - - - - - - - - ranking = 8.2501572891103E-5keywords = insufficiency (Clic here for more details about this article) |
8/28. IMAGe syndrome: a complex disorder affecting growth, adrenal and gonadal function, and skeletal development.IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, genital abnormalities; MIM 300290) is a multisystem disorder with a broad phenotype, which, if unrecognized, may result in major and possibly life-threatening complications. Initial clinical features overlap with those of Russell-Silver syndrome (RSS) and isolated growth hormone (GH) deficiency, conditions from which it must be distinguished. We report an Australian male with adrenal hypoplasia congenita (AHC) in association with IMAGe syndrome. The patient had intrauterine growth restriction (IUGR) and dysmorphic features comprising small, low-set ears, micrognathia, bilateral cryptorchidism, micropenis, and skeletal abnormalities. Signs of adrenal insufficiency occurred at aged 4.6 years. Our patient differs from those previously described by the late onset of adrenal insufficiency and the presence of GH deficiency. IMAGe is a complex syndrome involving dysmorphic features; disorders of growth, gonadal, and adrenal function; and skeletal abnormalities.- - - - - - - - - - ranking = 8.2501572891103E-5keywords = insufficiency (Clic here for more details about this article) |
9/28. Maternal uniparental disomy 16 and genetic counseling: new case and survey of published cases.uniparental disomy (UPD) is the occurrence of both homologous chromosomes from one parent. Maternal UPD(16) is the most often reported UPD other than UPD(15); almost all cases are associated with confined placental mosaicism (CPM). Most of maternal UPD(16) cases are characterised by intrauterine growth retardation (IUGR) and different congenital malformations. Maternal UPD(16) has therefore been suspected to have clinical effects: however, the lack of uniqueness and specificity of the birth defects observed suggests that the phenotype may be related in parts to placental insufficiency. We report on a new case of maternal UPD(16) associated with low level trisomy 16 mosaicism in placenta and fetus. IUGR was noticed at 19 gestational weeks and the fetus died intrauterine. Apart from different craniofacial dysmorphisms she showed anal atresia. While IUGR is probably associated with trisomy 16 mosaicism, anal atresia is more characteristic for maternal UPD( 16). Considering the features in our patient as well as those in maternal UPD (16) cases from the literature, indications for UPD (16) testing can be defined: They include trisomy 16 mosaicism, IUGR and congenital anomalies (anal atresia, congenital heart defects). However, there is an overlap of clinical signs in mosaic trisomy 16 cases mosaic for maternal UPD(16) as opposed to those mosaic for biparental disomy 16. The management of trisomy 16 pregnancies should not differ from those in which maternal UPD(16) is confirmed. Therefore, a prenatal testing for UPD(16) is not useful, but it should be offered postnatally. The molecular genetic proof of maternal UPD(16) excludes an increased recurrence risk for the family for further pregnancies.- - - - - - - - - - ranking = 1keywords = placental insufficiency, insufficiency (Clic here for more details about this article) |
10/28. Molecular cytogenetic characterization of ring chromosome 15 in three unrelated patients.We report molecular cytogenetic characterization of ring chromosome 15 in three unrelated male patients with the karyotype 46,XY,r(15). One was a stillborn child with several malformations, and the other two cases showed pre- and postnatal growth retardation and developmental delay, common features for ring chromosome 15 syndrome. One of these patients also displayed clinical features resembling prader-willi syndrome (PWS). To delineate the extent of the deletion on chromosome 15, we have carried out fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs) mapping to the distal long arm of chromosome 15. The deletion breakpoints clustered within a 4.5-6.5 Mb region proximal to the 15q telomere. Two deletions involved the same known genes, while the largest deletion observed in the stillborn child involved three additional genes, including the COUP-TFII gene, which has been suggested to play a role in heart development. The heart malformations, which are observed in this patient, are thus likely to be due to hemizygosity/haploinsufficiency of the COUP-TFII gene. In all three patients, the insulin-like growth factor i receptor gene (IGF1R) gene was deleted supporting the association between IGF1R and growth retardation seen in ring chromosome 15 syndrome.- - - - - - - - - - ranking = 4.1250786445552E-5keywords = insufficiency (Clic here for more details about this article) |
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