bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facial effects of fetal alcohol exposure: Assessment by photographs and morphometric analysis
Authors: Clarren Sterling K. , Sampson Paul D. , Larsen Jeannie , Donnell Deborah J. , Barr Helen M. , Bookstein Fred L. , Martin Donald C. , Streissguth Ann P. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis study was designed to assess the limits of alcohol‐related facial dysmorpho‐genesis. Standard full face and lateral facial photographs were obtained on 21 7‐year‐old children who had been exposed gestationally to known, heavy quantities of ethanol. Only two of these children had been previously considered to have definite fetal alcohol syndrome (FAS). Similar photographs of 21 other 7‐year‐old children with negligible gestational ethanol exposure were obtained for control purposes. Copies of the 42 photographs were given to each of seven expert clinicians who were asked to select any child with an FAS‐related facial appearance. Six of seven judges were accurate in identifying children with high levels of alcohol exposure as having a fetal alcohol‐affected face. A set of homologous points on the photographs were then digitized and analyzed by newly developed morphometric methods to determine the facial shape characteristics that distinguish the selected photographs of highly exposed children. The analysis confirmed that the judges specifically identified children with facial changes consistent with those previously published as defining the face of the FAS: short palpebral fissures, a relatively long and flat midface, and a retrusive mandible. This methodology may be useful in more accurately delineating the facial phenotype in other conditions diagnosed primarily on the basis of subjective clinical criteria.
The bingo model of survivorship. III. Genetic principles
Authors: Murphy Edmond A. , Trojak J. E. , Opitz John M. 
Published: June 2005

AbstractThe broad relationships are explored between the genetic and the phenotypic structures of the bingo‐gamma model (ie, the shortest waiting time among competing, independent, multiple‐hit systems). Finite algorithms are derived to compute in closed form the joint and marginal distributions; the distribution, density, and hazard functions of time to failure; the respective total probabilities of dying from failure of each competing system; and the raw and central moments. The algorithm is the computer counterpart of a generating function. The number of competing systems and their individual orders and transition parameters may be chosen at will. Classical Galton‐Fisher theory does not apply: neither means nor variances are additive nor are their effects homogeneous; rather, those systems with shorter mean survival more or less mask the impact of those with longer means. Thus even huge differences among means for alleles of any one component may be almost totally concealed phenotypically; even the maximal genetic covariation may in practice remain totally unrecognized and the heritability estimated close to zero. The proportional specific mortality is a less capricious index and is naturally additive, but, though a monotonic function of the underlying parameters, it is neither linear nor homogeneous.
Dominantly inherited renal adysplasia
Authors: McPherson E. , Carey J. , Kramer A. , Hall J. G. , Pauli R. M. , Schimke R. N. , Tasin M. H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe are reporting on 7 families with both unilateral and bilateral renal agenesis (or severe dysplasia). This condition, termed hereditary renal adysplasia (HRA) [Buchta et al, 1973], is an autosomal dominant trait with incomplete penetrance and variable expression. Review of the literature on familial renal agenesis suggests that HRA is more common than previously supposed and may account for most recurrences of bilateral renal agenesis (BRA), even v/hen the parents are normal. There are no consistent phenotypic differences between sporadic and familial renal agenesis. Associated non‐urogenital anomalies, although more frequent in sporadic cases, have been reported in HRA. Use of several approaches, including the Weinberg Proband Method, segregation analysis, and empiric risk estimation, leads to the conclusion that autosomal dominant inheritance is the most likely pattern of transmission for most cases of renal agenesis. Penetrance is between 50% and 90%. Ultrasound study of the kidneys of parents, sibs, and other relatives is recommended in all families in which there is an individual with unilateral or bilateral renal agenesis. The empiric risk for recurrence of BRA in sibs has been estimated at 3.5% [Carter, et al, 1979] but in the offspring of affected or obligate heterozygotes for HRA, the empiric risk of bilateral severe renal adysplasia is 15–20%.
Cleft lip/palate‐oligodontia‐syndactyly‐hair alterations, a new syndrome: Review of the conditions combining ecodermal dysplasia and cleft lip/palate
Authors: Martínez R. Benjamín , Monasterio A. Luis , Pinheiro Marta , Freire‐Maia Newton , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a noninbred girl with cleft lip and palate, complete absence of deciduous teeth, hypodontia of permanent teeth, hair alterations, hypertelorism, midface hypoplasia, abnormal EEC, syndactyly, and other findings. Her mother had minor anomalies which could represent the mild expression of a gene. A review on the conditions combining ectodermal dysplasia and cleft lip/palate is presented.
Segregation of inverted chromosome 13 in families ascertained through liveborn recombinant offspring
Authors: Pai G. S. , Shields Sally M. , Houser Patricia M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn humans pericentric inversions are rare structural chromosome abnormalities. Reproductive consequences of inversion heterozygosity depend upon many variables such as the chromosomes involved, the location of breakpoints, frequency of crossovers in the inverted segment, functional impairment of the gametes produced, and the viability of unbalanced zygotes that form. Therefore, each pericentric inversion may be studied as a unique mutation. This paper analyzes the segregation of inversion 13 chromosomes resulting from breaks at bands 13pl2 and 13q21/22 in 11 apparently unrelated families. Ten of these families were ascertained through malformed fetuses or infants with a recombinant 13 duplication q, deletion p chromosome.
The Neu–Laxova syndrome in female sibs: Clinical and pathological features with prenatal diagnosis in the second sib
Authors: Tolmie J. L. , Mortimer G. , Doyle D. , McKenzie R. , McLaurin J. , Neilson J. P. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on affected sisters with the Neu–Laxova syndrome. Prenatal diagnosis of the condition was achieved by serial ultrasound examinations which demonstrated abnormal fetal growth in the second affected fetus before 24 weeks gestation.
Nasopharyngeal carcinoma, aplastic anemia, and various malignancies in a family: Possible role of Epstein‐Barr virus
Authors: Schimke R. Neil , Collins Debra , Cross Donald , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a family ascertained because of sibs affected with nasopharyngeal carcinoma. Other relatives had aplastic anemia or other malignancies and most were born of consanguineous parents. Epstein‐Barr virus has been strongly implicated in the pathogenesis of nasopharyngeal carcinoma. It has also been suggested as a cause of aplastic anemia and other neoplasms. We postulate that this extensive German‐Mennonite family has a heritable defect in the immune response to Epstein‐Barr virus making its members at excessive risk for a number of different malignancies. This immunologic predisposition may be HLA associated and appears to be inherited as an autosomal recessive trait.
Trisomy 18 and hepatic neoplasia
Authors: Dasouki Majed , Barr Mason , Reynolds James F. 
Published: June 2005

AbstractA 2 9/12‐year‐old girl with trisomy 18 presented with a 3‐week history of low grade fever, abdominal distention, and hepatosplenomegaly. Abdominal cytotomography (CT) scan showed hepatic infiltration with a tumor mass presumed to be hepatoblastoma. She deteriorated rapidly and died 3 weeks later. No autopsy and/or biopsy could be done.
Variable expression in ankyloblepharon–ectodermal defects–cleft lip and palate syndrome
Authors: Greene Steven L. , Michels Virginia V. , Doyle John A. , Reynolds James F. 
Published: June 2005

AbstractThe ankyloblepharon‐ectodermal defects‐cleft lip and palate (Hay‐Wells) syndrome is a rare autosomal dominant form of congenital ectodermal dysplasia. It is characterized by coarse, wiry, sparse hair; dystrophic nails; slight hypohidrosis; scalp infections; ankyloblepharon filiforme adnatum; hypodontia; maxillary hypoplasia; and cleft lip and palate. To date, 12 patients have been reported; however, the diagnosis has been questioned in 3 of these patients. We report 2 additional patients, one of whom has nasal speech but not cleft palate, in contrast to all other reported patients. This entity must be distinguished from numerous other forms of ectodermal dysplasia, especially those forms that can be associated with oral clefts and/or ankyloblepharon.
Dyssegmental dysplasias: Clinical, radiographic, and morphologic evidence of heterogeneity
Authors: Aleck Kirk A. , Grix Art , Clericuzio Carol , Kaplan Paige , Adomian Gerald E. , Lachman Ralph , Rimoin David L. , Hall Judith G. 
Published: June 2005

AbstractThe dyssegmental dysplasias are lethal forms of neonatal short‐limbed dwarfism in which vertebral segmentation defects and short, thick, bowed long bones are the prominent radiographic features. Clinically, unusual facies, short neck, narrow thorax, cleft palate, and reduced joint mobility are commonly seen. To date, 18 cases of dyssegmental dysplasia have been reported. Reports of three pairs of affected sibs suggest autosomal recessive inheritance. We have studied eight additional cases of dyssegmental dysplasia, including one pair of affected sibs. Clinical, radiographic, and histologic examination of these new cases and review of the literature demonstrates the presence of at least two distinct forms of dyssegmental dysplasia. The milder form, “dyssegmental dysplasia, type Rolland‐Desbuquois,” is characterized clinically by frequent survival beyond the newborn period and by distinct radiographic changes resembling Kniest dysplasia. The severe form, “dyssegmental dysplasia, type Silverman‐Handmarker,” is charac‐terized by stillbirth or death within the first few days of life and by distinct and more severe radiographic changes. In addition, we have demonstrated chondroos‐seous morphologic differences between the two disorders by light and electron microscopy. We conclude that there are at least two forms of dyssegmental dysplasia, each autosomal recessive, which can be delineated on clinical, radio‐graphic and morphologic grounds.
Radial ray defect and Duane anomaly: Report of a family with autosomal dominant transmission
Authors: MacDermot Kay D. , Winter Robin M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a family in which a mother and her 2 offspring presented with bilateral radial defects and absent thumbs. In addition, Duane anomaly was present in both offspring, one of whom also had anal stenosis. Clinical investigation showed no skeletal, cardiac, or urogenital abnormalities. Autosomal dominant transmission of radial defects is suggested, with Duane anomaly and anal stenosis representing manifestations of the same gene.
Epidemiology of ambiguous genitalia in South America
Authors: Castilla Eduardo E. , Orioli lêda M. , Lugarinho Regina , Dutra Graca , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe present descriptive epidemiologic data on ambiguous genitalia (AG), obtained in the period 1967‐1982 by the Latin American Collaborative Study of Congenital Malformations (ECLAMC) through 70 participating hospitals located in 34 cities of 9 South American countries. The observed prevalence rate for isolated AG was about 1/20,000 births, with at least 1/4 and probably as much as 1/2 due to congenital adrenal hyperplasia. When AG cases associated with other congenital anomalies were also considered, the overall frequency of AG was 1/6,900 total births (1/10,000 for live and 1/350 for stillbirths). The prevalence rates were homogeneously distributed among the different countries, and there was a stable secular trend. AG was more frequent in nontropical than in tropical areas of South America, and there was a significant seasonal variation with its acrophase in August (winter). A case‐control analysis of 14 risk factors showed an association of AG with a prenatal history of acute maternal illnesses. These data do not support an etiological relationship between AG and hypospadias.
Onset in the seventh decade and lack of symptoms in heterozygotes for the TTRMet30 mutation in hereditary amyloid neuropathy—type I (Portuguese, Andrade)
Authors: Sequeiros Jorge , Saraiva Maria João Mascarenhas , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn a Portuguese‐American family with hereditary amyloid neuropathy (familial amyloidotic polyneuropathy), onset was in the seventh decade in all affected relatives. Another unusual characteristic was their origin from the Portuguese island of Madeira. In spite of this, the mutant transthyretin (TTRMet30) (the same variant prealbumin that is the circulating precursor of AFP protein in the classic Portuguese patients) could be found in the propositus plasma. In addition, three other asymptomatic relatives (ages 90, 73, and 48) were shown to carry the mutation.Late onset and incomplete penetrance, at a clinical level, raise problems for presymptomatic detection of mutant TTR, as these tend to cluster in families. When counseling asymptomatic heterozygotes, we must consider intra‐familial correlation in age‐of‐onset, and the distribution of age‐of‐onset including age of unaffected heterozygotes.This family poses interesting questions regarding pathogenesis of this degenerative process and the influence of other genetic factors, such as modifiers, epistasis, and polymorphism of the TTR genes or their regulators. A cis‐effect of a gene linked to the mutant gene, decreasing the synthesis of the mutant TTR and keeping a sufficient amount of the normal one in circulation, or producing some cofactor for TTR, could also explain late onset and apparently incomplete penetrance; the occasional finding of classic forms in these families would be the result of recombinatory events.
Common fragile sites: Their prevalence in subjects with constitutional and acquired chromosomal instability
Authors: Tedeschi Bruna , Porfirio Berardino , Vernole Patrizia , Caporossi Daniela , Dallapiccola Bruno , Nicoletti Benedetto , Neri Giovanni 
Published: June 2005

AbstractChromosomal fragile sites that are inducible by methotrexate and aphidicolin are frequent in the human population. To assess the frequency and distribution of these common fragile sites, we performed a cytogenetic survey on lymphocytes from subjects known to be particularly prone to breakage because of constitutional chromosomal instability, the possession of a rare fragile site, or Panconi anemia. Furthermore, a group of cancer patients was included in this study in view of possible acquired chromosomal instability. Lymphocyte chromosomes from several healthy donors were analyzed under identical conditions. We found that methotrexate‐ and aphidicolin‐induced fragile sites are widespread in the general population, showing a similar breakpoint distribution. Ten fragile sites (3pl4, 16q23, 2q32, 6q25, 4pl6, 4q31, 14q24, 1p31, 20pl2, 7q21) were observed in at least 40% of the individuals among the different groups. Our data point out a significantly increased breakage, induced by aphidicolin in lymphocytes from cancer patients and, to a lesser extent, from rare fragile sites carriers. These results suggest that common fragile sites are enhanced in some constitutional and acquired conditions.
Walker‐Warburg syndrome with cleft lip and cleft palate in two sibs
Authors: Burton Barbara K. , Dillard Robert G. , Weaver R. Grey , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractTwo sibs are reported with Walker‐Warburg syndrome including hydrocephalus, agyria, anterior chamber dysgenesis, and encephalocele. In addition, both had cleft lip and cleft palate and intrauterine growth retardation, findings not previously noted in this condition.
Animal model: Dysmorphogenesis and death in a chicken embryo model
Authors: Fineman Robert M. , Schoenwolf Gary C. , Prieur David J. 
Published: June 2005

AbstractThe chicken embryo is a useful animal model for investigating problems in developmental biology and teratology. Here we report data that further define the causes of 2 different patterns of malformation (one associated with amnion abnormalities, the other with isolated neural tube defects) and death induced by making a window in the shell and subshell membranes during the first day of incubation. The interpretation of these data suggests to us the following hypotheses. An early amnion deficit spectrum or syndrome (EADS) in chicken embryos is caused by a brief (less than 10 sec) perturbation that occurs during the windowing procedure. This perturbation results in an acute increase in mechanical tension to the developing embryo and support structures, dehydration localized to the area of the blastoderm, and/or increased friction between the blastoderm and overlying vitelline and shell membranes. Isolated neural tube defects (NTDs) are caused by a longer perturbation (> 3 hr) consisting of increased mechanical stress across the blastoderm. The mechanical stress is associated with the introduction of a new air space over the animal pole of the yolk during windowing. The new air space causes the shape of the yolk to change (ie, to be deformed), resulting in an increase in mechanical tension across the vitelline membrane and blastoderm. NTDs involving the head are associated with significant early embryonic mortality, whereas those involving the trunk are not. Death may also be caused by cardiovascular anomalies observed in EADS. It is concluded that disturbances in morphogenesis and death in this model are, therefore, the result of extrinsic forces (eg, mechanical stress, localized dehydration, or friction) acting on different tissue types at various critical times in development. Intensity and duration of these forces on the developing blastoderm are important variables.
Apparently new autosomal recessive syndrome of mental retardation, distal limb deficiencies, oral involvement, and possible renal defect
Authors: Buttiens M. , Fryns J. P. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis paper illustrates a syndrome of distal limb deficiency and oral defects in two sibs, a moderately mentally retarded man and his mildly retarded sister. Both have microretrognathia, microstomia, normal tongue, and symmetric severe limb deficiencies. This seems to be a previously undescribed syndrome. The nosology of the different orofacial syndromes associated with distal limb deficiencies is discussed.
Genetic ascertainment with heterogeneous risk
Authors: Murphy Edmond A. , Meyers Deborah A. , Rohde Charles A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAnalysis of the bias of ascertainment is reformulated to deal with more general patterns commonly encountered in practice. The goal is to provide a unifying theory that will both replace the traditional, rather piecemeal, treatment of the problem and free it from certain restrictive assumptions. A compact algebraic method is furnished for analyzing the properties of the distributions by means of the probability generating function (PGF). The scope of the generalization is illustrated by applying it to the various classical patterns of bias of ascertainment. It is extended to other patterns in which the conditions of ascertainment, though more plausible, are also logically more complicated. It also accommodates cases hitherto inadequately dealt with, such as where the segregation ratios are heterogeneous (for example because of age‐dependence); and cases where the ascertainment function is of arbitrary form and denies us such valuable, but demanding, assumptions as independence. Not only is the result unifying, but it leads to usable results in specific applications such as diseases that depend on age or birth order. While the commonest applications are in human genetics, there are many other issues (such as the use of batteries of tests) in which it is equally important.
Duplication 7p in a family with t(7;11): Association with anomalies of the anterior cranial base
Authors: Odell J. Michael , Siebert Joseph R. , Bradley Cynthia , Salk Darrell , Reynolds James F. 
Published: June 2005

AbstractDuplication 7p has been observed in association with several balanced translocations. Of eight previously recorded cases, only one exhibited duplication of the entire short arm of chromosome 7. We report on a newborn infant with multiple congenital anomalies and an abnormal chromosome constitution: 46,XX, −11, +der(11),t(7;11) (p11.1;p15.5)mat. The proposita appeared to possess an isolated duplication of the entire short arm of 7. The patient died at age 4 days because of respiratory complications of meconium aspiration. Clinical and postmortem findings included craniocerebral asymmetry, craniosynostosis of a lambdoid suture, arhinencephaly, hypertelorism, anomalies of the ethmoidal portion of the cranial base, large anterior fontanelle, low set ears, ventricular septal defect (VSD), dysplastic tricuspid and pulmonic valves, hypoplastic genitalia, bilateral dislocated hips, and other minor limb malformations.
Isolation of human Y chromosomal major repetitive sequences from a flow‐sorted Y chromosomal library
Authors: Nishioka Yutaka , Lamothe Estelle , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe human Y chromosome is highly heterochromatic and consists mainly of repetitive sequences, of which 3.4 kb HaeIII or EcoR1 fragments represent the most abundant species. From a flow‐sorted human Y chromosomal library, we isolated 15 clones containing sequences highly homologous to this major repetitive sequence. Although the size of inserts varied from 0.7 to 3.8 kb, their hybridization patterns to human genomic DNA were indistinguishable from each other. These repetitive sequences unambiguously detected the presence of the Y chromosome in a male–female DNA mixture of which 5% was derived from male cells. Thus, these clones would be useful molecular tools to detect contaminating male cells in clinical materials.
Pterygium colli medianum and midline cervical cleft: Midline anomalies in the sense of a developmental field defect
Authors: Godbersen Sönke , Heckel Volker , Wiedemann H.‐R. , Opitz John M. 
Published: June 2005

AbstractWe report on 2 patients (and review a third) with a vertical midline neck web which extends from the lower symphysis of the mandible to a variable extent down to the jugular notch. This uncommon congenital anomaly, previously reported primarily in the (plastic) surgery literature, is interpreted as the mildest form and most dorsal extension of anterior midline cleft defects which include the supraumbilical raphé and cleft sternum with or without congenital hemangiomata. By analogy with the former, and the fact that in a boy with a severe cervical midline web there was a cleft of the upper sternum, we interpret this neck‐web as a developmental field defect. It is a sporadic anomaly but may be associated with other midline malformations including congenital heart defect(s). Thus, finding such a web at birth should prompt a careful search for other anomalies.