bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of Metacarpal II dimensions in boys during adolescence
Authors: Beunen G. P. , Blimkie C. J. R. , Lefevre J. , Dequeker J. , Verbiest M. , Geukens M.
Published: June 2005

The stability of radiogrammetrically determined Metacarpal II (M II) bone dimensions was determined in 184 Belgian boys between 13 and 18 years of age. Stability was assessed by Fisher z transformations of Pearson correlations between discrete measurement intervals and by structured covariance analysis incorporating compound, banded, and autoregressive models. Adjacent‐age stability (1‐year measurement interval) was high (0.82 ⩽ r ⩽ 0.97) for all metacarpal dimensions for all approaches, but stability coefficients decreased with increasing measurement interval for the correlational, banded, and autoregressive analyses. Despite the interval‐related decline, correlations remained moderate to high, ranging between 0.65 and 0.97 for the correlational analyses and 0.58 and 0.91 for the covariance analyses, indicating a moderate to high degree of stability of M II dimensions in males during adolescence. Periosteal diameter demonstrated the greatest stability of all metacarpal variables for all statistical analyses. Of the covariance models, the compound model provided the poorest fit to the data, and only for metacarpal length and periosteal diameter did the more complex (6 parameters) banded model provide a significantly better fit than the simpler (2 parameters) autoregressive model. These results indicate that M II bone dimenions are fairly stable in males between 13 and 18 years of age and that the autoregressive model, with the exception of metacarpal length and periosteal diameter, provides as good a fit to the metacarpal data as the more complex banded model. © 1994 Wiley‐Liss, Inc.
Body composition measures from underwater weighing and dual energy X‐ray absorptiometry in black and white girls: A comparative study
Authors: Morrison John A. , Khoury Philip R. , Campaigne Barbara N. , Chumlea W. M. Cameron , Specker Bonny , Campaign Barbara N. , Guo Shumei S.
Published: June 2005

The purpose of this study was to compare estimates of body composition in two ethnic groups, 31 black and 38 white girls 10 through 16 years of age, to establish accurate and precise laboratory standards for field measures of body composition in the NHLBI Growth and Health Study HC 55025. The dual energy X‐ray absorptiometry (DXA) measures of fat free mass (FFM) and % body fat (%BF) were made using Hologic QDR‐1000/W. Corresponding values of FFM and %BF from underwater weighing (UWW) were determined using the two‐component model of Siri, and these were corrected using the model of Lohman for white girls only. In the comparison of the different models and methods, the two‐component model overestimated FFM compared to estimates from DXA for black girls, as did the corrected Lohman model for white girls. The two‐component model significantly overestimated %BF in both white and black girls compared to corresponding estimates from DXA. The ratio of bone mineral content (BMC)/FFM affected the degree of %BF differences in black girls but not in white girls. Also, as the density of FFM increased or approached adult status in black girls (BMC/FFM increased), differences between the two‐component model and estimates from DXA decreased. In both groups of girls, the relationship of %BF from UWW and DXA are a function of the level of body fatness. DXA values of %BF are greater than those from UWW under about 24% body fat, but the converse occurs above 25% body fat. The inability of UWW using the two‐component model to account for the body composition in these girls can be corrected in part by measuring the variables for a multicomponent model or more easily by using DXA estimates of body composition. © 1994 Wiley‐Liss, Inc.
Total lung capacity in Andean highlanders
Authors: Greksa Lawrence P.
Published: June 2005

Total lung capacity (TLC), residual volume (RV), and vital capacity (VC), as well as related measures of pulmonary function, were assessed in a sample of 39 male and 23 female native highlanders of Aymara ancestry (20.1–28.8 years) who were residing in La Paz, Bolivia (average altitude of about 3,600 m). After controlling for body and chest size, most measures of respiratory function were significantly larger in males than females (P < .05). Absolute TLC (1 BTPS) was significantly larger in the La Paz Aymara males than in highland Peruvian or Tibetan males (P < .05) but, after controlling for body size, TLC was only 1 and 4% larger in the La Paz Aymara than in highland Peruvians or Tibetans, respectively. Also, comparison of the body size‐adjusted percentage increases in TLC, VC and RV above U.S. sea‐level reference values in selected highland populations indicated that the enhanced TLCs of highlanders are primarily due to an enhancement of RV and secondarily due to an enhancement of VC. © 1994 Wiley‐Liss, Inc.
Neonatal and maternal anthropometric characteristics in a high altitude population of the western Himalaya
Authors: Wiley Andrea S.
Published: June 2005

A study of neonatal anthropometric characteristics was undertaken in Ladakh, India, a region comprising the western portion of the trans‐Himalayan plateau. The object was to better understand the dynamics of high altitude adaptation in the Himalaya. In a largely native sample of 168 women and their newborns, mean birth weight was 2,764 g, mean length was 48.02 cm, and mean Ponderal Index (PI) was 2.49. Female newborns were significantly lighter and shorter than males. Overall, 27% of newborns fell into the standard category of infants at increased risk of mortality ( < 2,500 g); 37% of females and 17% of males were so classified. In multivariate regression analysis, maternal weight and the sex and gestational age of the newborn were the only significant predictors of birth weight, but explained a small (18%) part of the variance. Compared to Andean and Tibetan samples, Ladakhi newborns were between 300 and 550 g lighter. This variation is explained, in part, by maternal characteristics, such as lower average parity, age, and weight. Reproductive capacity appears to be compromised in this population because of inadequate nutrition in the face of high energy demands of agricultural work, which may further compromise maternal adaptation to hypoxic conditions. The population of Ladakh has a relatively recent ancestry in this high altitude region and is likely a genetically heterogeneous population from an extensive history of immigration. Thus it is possible that the low average birth weight in Ladakh may also be influenced by inadequate genetic adaptation to hypoxia. © 1994 Wiley‐Liss, Inc.
Amniotic fluid testosterone and follicle stimulating hormone levels as indicators of fetal sex during mid‐pregnancy
Authors: Mennuti M. T. , Wu C. H. , Mellman W. J. , Mikhail G.
Published: June 2005

Midtrimester (14–22 weeks of gestation) amniotic fluid hormone levels were measured as indicators of fetal sex in 99 pregnancies (66 with a male fetus and 33 with a female fetus). Statistically significant didfferences in testosterone (T), androstenedione (A), and follicle stimulating hormone (FSH) levels were observed between pregnancies with fetuses of differing sex. No significant difference was observed for estrone (E1), estradiol (E2), or progesterone (P) levels.

Fetal sex was accurately predicted in 96 of 99 pregnancies using a criterion of T ≥ 100 pg/ml for males and in 94 of 99 pregnancies using a criterion of FSH ≥ 3 mIU/ml for females. In the 3 cases in which the fetus was male but the T level was < 100 pg/ml, the FSH was clearly in the male range. Likewise, in 5 cases in which the fetal sex was not correctly predicted by the FSH level, the T level confirmed the karyotype.

It is proposed that measurement of amniotic fluid testosterone levels would be of value in detecting errors in prenatal cytogenetic diagnosis when there is incorrect fetal sexing. It is suggested that FSH determinations be performed when the amniotic fluid testosterone does not confirm the karyotype, and that when there is a discrepancy between the karyotype and both of these measurements, repeat amniocentesis should be considered.
Pericentric inversion of chromosome 14 and the risk of partial duplication of 14q (14q31 → 14qter)
Authors: Trunca Carolyn , Opitz John M. , Kaye Celia I.
Published: June 2005

Cytogenetic analysis after conventional staining and Q‐banding demonstrated a pericentric inversion of chromosome 14 in the mother of a child with a mental retardation/multiple congenital abnormality syndrome and an abnormal chromosome 14. The proposita's partial duplication for the distal segment of 14q is apparently the result of crossing over within the inverted segment during meiosis. An attempt is made at assessing the risk that a carrier of the described pericentric inversion faces of having an abnormal child. The estimate of the risk depends on two factors: 1) the probability of a crossover occurring within the inverted segment during meiosis, and 2) the probability of a child with either of the two possible unbalanced recombinant chromosomes being born alive. An explanation is offered as to why some pericentric inversions confer a significant risk while others are so benign and occur with such a high frequency that they can be considered normal chromosomal variants, rather than chromosome aberrations.
Genetic studies on Cochin Jews in Israel: 1. Population data, blood groups, isoenzymes, and HLA determinants
Authors: Cohen T. , Levene C. , Yodfat Y. , Fidel J. , Friedlander Y. , Steinberg A. G. , Brautbar C. , Opitz John M.
Published: June 2005

The period in which Jews were first associated with Cochin and the Malabar coast was by tradition, after the destruction of the First Temple (586 BCE). Yet, the earliest evidence of Jewish settlements is from the tenth century CE. The largest group of Cochin Jews are the “Black Jews”, of whom about 4,000 live in Israel. A high frequency of consanguineous marriages prevailed among Cochin Jews. Their mean height and weight were low when they came to Israel in 1954; an increase in both was observed 20 years later.

Some of the allele frequencies of blood groups, isoenzymes, and HLA antigens were similar to those in other Jewish communities. In the high O, M, cde, and HLA‐A28 and the low cDE allele frequencies Cochin Jews resembled Yemenite Jews. A few allele frequencies, the high Fya, AK2 and the low Jka and Hp1, were similar to those observed in indigenous southern Indian populations. In most HLA antigen and haplotype frequencies the Cochin Jews showed a distribution similar to that observed in other Jews and Caucasoids. No comparable HLA data on southern Indian populations were available. The results indicate that Cochin Jews have similarities with Jews, in particular Yemenite Jews, and with the indigenous populations of southern India.
Genetic studies on Cochin Jews in Israel: 2. Gm and Inv data — polymorphism for Gm3 and for Gm1,17,21 without Gm(26)
Authors: Steinberg A. G. , Levene C. , Yodfat Y. , Fidel J. , Brautbar C. , Cohen T. , Opitz John M.
Published: June 2005

Serum samples from 223 Jews from Cochin, India were tested for Gm(1,2,3,5,6,13,14,17,21,26) and for Inv(1). Certain samples were also tested for Gm(15) and Gm(16).

The Cochin Jews are polymorphic for: 1) Gm3, a haplotype that does not lead to the formation of γ3, as was shown by tests of the serum of a homozygote, and 2) Gm1,17,21, a haplotype lacking Gm(26), which is ordinarily present in this haplotype. The Gm data indicate considerable admixture with southern Indians. There is no evidence for African admixture, such as has been found for all other Jewish populations studied thus far. The Inv data are similar to those for other Jewish populations.
Phenotype associated with ring 10 chromosome: Report of patient and review of literature
Authors: Michels Virginia V. , Driscoll David J. , Ledbetter David H. , Riccardi Vincent M. , Opitz John M.
Published: June 2005

A 15‐month‐old infant's peripheral blood chromosome analysis showed the following defects: 46,XY,r(10)(p15.3q26.1) in 84 cells, 45,XY,−r(10) in 13 cells, and 47,XY,r(10),+r(10) in one cell. Clinical abnormalities included growth retardation, microcephaly, prominent nasal bridge, macular hypoplasia, persistent pulmonary hypertension, and posterior urethral valves with hydronephrosis. Comparison of the phenotype of five other patients with a ring chromosome 10 with the present case showed the following common manifestations: growth retardation, microcephaly, undescended testes, hydronephrosis, and, in males, posterior urethral valves. To date, this last anomaly has not been seen in patients with either a del(10p) or a del(10q) abnormality.
The mucolipidoses: Identification by abnormal electrophoretic patterns of lysosomal hydrolases
Authors: Honey N. K. , Miller A. L. , Shows T. B. , Opitz John M.
Published: June 2005

The human mucolipidoses (ML) are characterized by abnormal activities and abnormal electrophoretic patterns of fibroblast lysosomal hydrolases. These altered mobility patterns can be used to confirm the clinical diagnosis of the four mucolipidoses. The mobility patterns of one nonlysosomal and seven lysosomal enzymes were tested in fibroblasts from two ML I (sialidosis type 2, infantile), fifteen ML II (I‐cell disease), eight ML III (pseudohurler poly‐dystrophy), and one ML IV patients. A single sialidosis type 2, juvenile, line was also examined. Characteristic mobility patterns were found which identify each of the four mucolipidoses. Both the ML I and sialidosis type 2 juvenile lines displayed anodal mobility patterns, but distinct differences between the two disorders were observed. Lysosomal hydrolases from ML II lines demonstrated reduced activities or had altered mobilities. Differing electrophoretic patterns demonstrated the presence of at least two groups within the clinical phenotype diagnosed as ML II, indicating heterogeneity. The ML III lines showed normal electrophoretic patterns for most lysosomal hydrolases. The ML IV line expressed normal mobilities for every enzyme studied, with a single exception. The electrophoretic patterns of only β‐hexosaminidase, acid phosphatase‐2, α‐galactosidase, and esterase A4were sufficient to identify and distinguish the different mucolipidosis types. Electrophoretic variation was also seen in liver but not kidney extracts from three ML II patients. β‐Hexosaminidase and α‐mannosidase B secreted into the medium by ML II and ML III fibroblasts had mobility patterns different from normal and from their intracellular patterns. These data suggest that the mucolipidoses are genetically distinct with heterogeneity within them.
A child with radius aplasia, cleft of lip and palate, microcephaly, and unusual chromosome findings
Authors: Butler Merlin G. , Russell Laura J. , Palmer Catherine G. , Bull Marilyn , Hodes M. E. , Opitz John M.
Published: June 2005

We report a child with malformation syndrome of microcephaly, asymmetrical radius aplasia, and cleft of lip and palate, who was mosaic for a chromosome marker and/or ring of unknown origin. In view of the reported cases of limb deficiency with chromosome abnormalities and the unlikelihood that the patient has a recognized genetic syndrome, the cause of the patient's syndrome may well be the extra chromosomal material.
Syndrome of total alopecia, multiple skeletal anomalies, shortness of stature, and mental deficiency
Authors: van Gelderen H. H. , Opitz John M.
Published: June 2005

This is a report of a 16‐year‐old boy with mental deficiency, shortness of stature, peculiar face and skull, multiple skeletal anomalies, limb contractures, total alopecia, and probable hypothalamic hypogonadism. A striking resemblance exists between this case and a female adolescent described in 1980 by Schinzel. It is suggested that these two cases represent a previously unrecognized syndrome. The fact that this boy was born from a first‐cousin marriage suggests autosomal recessive inheritance.
Omphalocele and multiple severe congenital anomalies associated with osteodysplasty (Melnick‐Needles syndrome)
Authors: von Oeyen Paul , Holmes Lewis B. , Trelstad Robert L. , Griscom N. Thorne
Published: June 2005

Osteodysplasty (Melnick‐Needles syndrome, MNS), a severe bone dysplasia with presumed autosomal dominant inheritance, has now been described in 24 individuals, with a predominance of females (21:3). We report an affected woman who gave birth to a male infant with omphalocele, hypoplastic kidneys, and the skeletal changes of this disorder; he died soon after birth. Histologic studies of the calvaria and long bones showed normal maturational sequences, but suggest that remodeling was not normal. This is the second known instance of a male infant with omphalocele and this skeletal dysplasia born to a woman with MNS. We suggest that the gene for the MNS may also cause a syndrome of multiple abnormalities that can be lethal and that this more severe phenotype in males may account for the altered sex ratio among reported cases. Both X‐linked dominant and autosomal‐dominant sex‐limited inheritance are feasible interpretations of the existing information.
A previously undescribed autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome with growth failure, lip/palate cleft(s), and urogenital anomalies
Authors: Malpuech G. , Demeocq F. , Palcoux J. B. , Vanlieferinghen P. , Opitz John M.
Published: June 2005

In four children from the same family, we have observed an association of mental retardation, dwarfism, hypertelorism, facial clefting and urogenital abnormalities. Clinical and laboratory data suggest that it is a previously undescribed genetic syndrome, ie, a pleiotropic autosomal recessive trait.
Paradoxical fixation of deleterious alleles in two‐locus systems with epistasis
Authors: Trojak Joseph E. , Murphy Edmond A.
Published: June 2005

The dynamics of four deterministic models of interaction between two Mendelian loci are explored numerically. At one locus there are two hypostatic alleles: h, the wild type and H, a deleterious mutant that in either heterozygous or homozygous state (depending on the specifics of the model) produces an abnormal phenotype. At another arbitrarily linked epistatic locus there are two alleles: e, the wild type with no effect on the expression of the H locus, and E, an epistatic mutant that in heterozygous or homozygous state (again, depending on the specifics of the model) blocks the expression of H. The parameters are the initial gamete frequencies, the recombination fraction, the genotypic viabilities, and the forward and back mutation rates at each locus. The He haplotype is eventually eliminated (unless back mutation occurs) from the population. If mutation is ignored, the evolutionary outcome is determined by the initial gamete frequencies and is either (1) an edge equilibrium comprising one pair of haplotypes only (he and He, or he and hE, or hE and HE, or He and HE, or, if there is no recombination, he and HE or hE and He); or (2) a corner equilibrium consisting of a single gametic type. Given that the forward mutation rates at both loci are greater than the back mutation rates, then the outcome is always the corner equilibrium in which HE is universal (apart from transient perturbations by mutation). In the process of fixation, the phenotypic impact of the deleterious allele H becomes neutralized by the epistatic allele E. The rate at which the initially harmful gene replaces the wild type gene depends on the recombination fraction, the genotypic viabilities, and the mutation rates.
Phenotypic heterogeneity in neural tube defects: A clue to causal heterogeneity
Authors: Martin R. A. , Fineman R. M. , Jorde L. B. , Opitz John M.
Published: June 2005

We report here retrospective data on 991 liveborn and stillborn infants with neural tube defects (NTDs) born to Utah residents from January 1, 1940 to December 31, 1979. Data were obtained from multiple sources including approximately 1.25 million vital statistics records and several hundred physician and hospital charts. Causal heterogeneity among NTD patients is presumed because 6% of our cases have other congenital anomalies not part of the NTD field defect. A significant association of NTDs with oral clefts is noted. Sex ratios and empiric recurrence risks for isolated NTDs and NTDs associated with other major malformations are also calculated.
Benign familial neonatal‐infantile seizures
Authors: Kaplan Robert E. , Lacey Daniel J. , Opitz John M.
Published: June 2005

We report on an autosomal dominant neonatal‐infantile seizure disorder and offer criteria for establishing the diagnosis and guidelines for the evaluation and treatment of this disorder. Long‐term anticonvulsant treatment usually is not required. The subsequent risk of a recurrent seizure disorder depends on whether other affected relatives developed a seizure disorder later in life. This disorder may have at least two different neonatally indistinguishable forms: one having an increased empiric risk (20%) of subsequent epilepsy, and a second which carries no increased risk. These familial neonatal‐infantile seizures are termed “benign” since they are not associated with subsequent psychomotor retardation.
Acrofacial dysplasia resembling geleophysic dysplasia
Authors: Spranger J. , Gilbert E. F. , Flatz S. , Burdelski M. , Kallfelz H. C.
Published: June 2005

We report on a 12‐year‐old girl with acrofacial dysplasia, growth retardation, joint contractures, mitral valve incompetence and focal hepatic storage of material reacting histochemically as glycoprotein. The patient's phenotype resembles that of patients with geleophysic dysplasia but differs with respect to facial appearance, milder changes of hand bones and normal capital femoral epiphyses. It is undecided if her disorder is part of a wider phenotypic spectrum of geleophysic dysplasia or a different entity.
Impact of PKU on the reproductive patterns in collaborative study families
Authors: Burns Joan K. , Azen Colleen G. , Rouse Bobbye , Vespa Hazel
Published: June 2005

Factors that relate to reproductive patterns in 129 families after the birth of a child with phenylketonuria (PKU) include birth order of the index child, age of the parents at the birth of the index child, and expressed intentions of the parents whether or not to have additional children. Factors that do not correlate with reproductive histories include knowledge of the genetic and metabolic nature of PKU, the relationship of PKU to mental retardation and special diet, parental upset about the diagnosis, sex of the affected child, parental IQ, religion, education, and social class.

Correlations found related to the question, “Is PKU the reason you don't want more children?” include stress factors in family functioning, mother's upset with the diagnosis, father's concerns about being a carrier, sex of the child with PKU, and degree of knowledge about PKU.

Many of the Collaborative Study clinics tend to be more concerned about the consequences of PKU on the family than on society, and feel that families should receive genetic counseling to determine their reproductive risks and future plans. Upon self‐report, many clinics declare their counseling to be either “completely nondirective” or making a “conscious effort to be nondirective”.
Gene dosage studies supporting localization of the structural gene for galactose‐1‐phosphate uridyl transferase (GALT) to band p13 of chromosome 9
Authors: Shih Ling Yu , Suslak Lorraine , Rosin Irit , Searle Bernard M. , Desposito Franklin
Published: June 2005

A newborn male was diagnosed as having a duplication of distal 9p material by GTG banding analysis. Gene dose studies for galactose‐1‐phosphate uridyl transferase (GALT) were performed on the patient, his mother (the balanced translocation carrier), a 3‐year‐old 47,XY + 9p male control, a 30‐year‐old woman with mosaic trisomy 9p, a newborn female control infant with complete trisomy 9, and age‐matched chromosomally normal control individuals. The findings support previous evidence that the GALT locus is at band p13 of chromosome 9.
The split‐hand and split‐foot anomaly in a central African Negro population
Authors: Viljoen D. L. , Beighton P.
Published: June 2005

The split‐hand and split‐foot anomaly (ectrodactyly) was identified in five individuals of three generations of a kindred from a remote African Village; seven more were known to be affected in a further two generations. The malformations were confined to the hands and feet and inherited as an autosomal dominant trait with variable expression. Bilateral triphalangeal thumbs were present in three of the affected individuals.
Reproduction in XYY males: Two new cases and implications for genetic counseling
Authors: Grass F. , McCombs J. , Scott C. I. , Young R. S. , Moore C. M.
Published: June 2005

We present two children—one, 47, XY, + mar, and the other, 47, XY, +21. Both fathers were found to have a 47, XYY chromosome constitution. The initial assumption was that the fathers' aneuploid conditions contributed to those of the offspring. However, the derivation of the marker chromosome could be paternal, maternal, or postzygotic, and examination of polymorphic structures of the number 21 chromosomes of the child with Down syndrome and his parents suggested maternal derivation of the supernumerary 21. To explore further the reproductive risks of an individual with the XYY cónstitution, previous reports of reproductive performance and testicular histology are examined as are two theories which suggest XYY males may be at an increased risk of producing aneuploid progeny. Based on these reports, recommendations are made for testing XYY males prior to genetic counseling.
Possible causal heterogeneity in spina bifida cystica
Authors: Toriello Helga V. , Higgins James V. , Opitz John M. , Reynolds James F.
Published: June 2005

A study was performed to determine whether causal heterogeneity can be demonstrated among the nonsyndromal spina bifida cysticas based on the vertebral level of the defect. Two groups were compared, probands with defects at or above T 11, likely representing defects of neuralization, and probands with defects at or below T 12, likely defects of canalization. Differences between the two groups were found with respect to reproductive history and occurrence of other malformations. A high degree of concordance for the type of defect among affected sib pairs was also observed. These findings indicate that there is probably heterogeneity within the spina bifida cysticas based on the level of the defect.
Laryngeal cleft: Report of eight patients and a review of the literature
Authors: Tyler Donald C. , Opitz John M. , Reynolds James F.
Published: June 2005

Eight cases of laryngeal cleft are presented and the literature on this topic is reviewed. Patients most frequently present with stridor, respiratory distress, or a history of choking while feeding. A number of cases are found at autopsy or surgery. Laryngeal cleft frequently is found associated nonspecifically with tracheoesophageal fistula, cleft lip and cleft palate, and congenital heart defects. Laryngeal cleft may be a component manifestation of several syndromes, eg, the G syndrome, and the Pallister‐Hall syndrome of congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly. Surgical treatment is successful in more than 50% of the reported cases, depending on the extent of the cleft. Cleft larynx is most likely a developmental field defect, occurring coincidentally with separation of larynx and esophagus and closure of the larynx.
Hypopituitarism and septooptic “dysplasia” in first cousins
Authors: Blethen Sandra L. , Weldon Virginia V. , Opitz John M. , Reynolds James F.
Published: June 2005

Although familial forms of hypopituitarism are known, to our knowledge familial septooptic “dysplasia” in association with hypopituitarism has not been reported. We describe two first cousins with panhypopituitarism, one of whom had septooptic dysplasia. We discuss the possibility that septooptic dysplasia‐hypopituitarism may be inherited as an autosomal dominant, or recessive, or multifactorial trait.
Sternal malformation/vascular dysplasia association
Authors: Hersh J. H. , Waterfill D. , Rutledge J. , Harrod M. J. E. , O'sheal S. F. , Verdi G. , Martinez S. , Weisskopf B. , Opitz John M. , Reynolds James F.
Published: June 2005

Sternal defects associated with superficial craniofacial vascular lesions are rare. We report on two additional patients with a sternal cleft and cutaneous, craniofacial hemangiomata to emphasize that this unusual combination of findings represents a recognizable sternal malformation/vascular dysplasia association. In addition, internal vascular lesions were also identified in these individuals, in one instance involving the upper respiratory tract and in the other the viscera. Although the pathogenesis of these findings is unclear, an early disturbance affecting midline mesodermal structures leading to lack of complete fusion of lateral sternal bands and overlying cutaneous tissue, or deficient formation of a proposed medioventral unpaired structure which may be involved in the formation of the sternum, and persistence and proliferation of midline angioblastic tissue may be possible mechanisms during the sixth to ninth gestational weeks. To date, all but one of the 15 known cases have been sporadic and no teratogen has been identified as a cause for these clinical manifestations. The presence of this association should signal the need to search for potentially life‐threatening internal hemangiomata.
Smith‐Lemli‐Opitz syndrome‐type II: Multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality
Authors: Curry Cynthia J. R. , Carey John C. , Holland Julie S. , Chopra Devinder , Fineman Robert , Golabi Mahin , Sherman Sanford , Pagon Roberta A. , Allanson Judith , Shulman Sally , Barr Mason , McGravey Vincent , Dabiri Cyrus , Schimke Neil , Ives Elizabeth , Hall Bryan D. , Opitz John M. , Reynolds James F.
Published: June 2005

In 1964, Smith et al described a syndrome of microcephaly, growth and mental retardation, unusual facial appearance, syndactyly of toes 2 and 3, and genital abnormalities. Major structural malformations and early death have been uncommon in the many subsequent literature reports. We report on 19 infants with a phenotype we propose to call Smith‐Lcmli‐Opitz syndrome (SLOS)‐Type II, in which major structural abnormalities, male pseudohermaphroditism, and early lethality are common. Of these 19 patients, 18 had postaxial hexaclactyly, 16 had congenital heart defect, 13 had cleft palate, and 10 had cataracts. Unusual findings seen in those patients at autopsy included Hirschsprung “disease” in five patients, unilobatod lungs in six, large adrenals in four, and pancreatic islet cell hypciplasia in three. Comparison of our cases to 19 similar literature cases suggests the existence of a distinct phenotype that may be separate from SLOS as originally described. It is also inherited as an autosomal recessive, as documented by occurrence in one pair of sibs in this study and recurrence in three reported families.
The Johanson‐Blizzard syndrome: A second report of full autopsy findings
Authors: Moeschler John B. , Polak Mark J. , Jenkins Jesse J. , Amato R. Stephen S. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a second patient with Johanson‐Blizzard syndrome with full autopsy. The findings are similar to those of the one other available case, but gross or fine CNS maldevelopment was not present; although small by weight, the brain showed no cytoarchitectural disturbance. Normal intellecutal development does occur in this syndrome and may relate to the variable effects of the deleterious gene on the developing CNS.
Mosaic trisomy 7 and renal dysplasia
Authors: Verp Marion S. , Amarose Anthony P. , Esterly John R. , Moawad Atef H. , Reynolds James F.
Published: June 2005

Trisomy 7 was detected in umbilical cord cells cultured from a fetus with renal dysplasia. Skin fibroblasts were diploid. Because of a paucity of liveborn infants with full trisomy 7, the phenotype is noi well described; however renal anomalies appear to be common with trisomy 7.
DOOR syndrome (deafness, onycho‐osteodystrophy, and mental retardation): Elevated plasma and urinary 2‐oxoglutarate in three unrelated patients
Authors: Patton M. A. , Krywawych S. , Winter R. M. , Brenton D. P. , Baraitser M. , Neri Giovanni
Published: June 2005

We describe three further children with the DOOR syndrome (deafness, onycho‐osteodystrophy and mental retardation). A severe seizure disorder and character‐istic facial appearance are part of the syndrome. Fourteen similar cases including the present patients are now on record. Autosomal recessive inheritance is likely.

An increased level of 2‐oxoglutarate in both plasma and urine has been found in our three patients. It is suggested there may be an inherited metabolic defect in this malformation syndrome.
Mental retardation, spasticity, and transverse limb defects
Authors: Zlotogora Joël , Reynolds James F.
Published: June 2005

We report on a mentally retarded boy with spastic paraplegia and a transverse defect of the left foot who was bora to consanguineous parents. This association of ectrodactyly, mental retardation, and spastic paraplegia was first reported by Jancar [1967].
Prenatal diagnosis of a dup(3p) with holoprosencephaly
Authors: Gillerot Yves , Hustin Jean , Koulischer Lucien , Viteux Vincent , Neri Giovanni , Opitz John M.
Published: June 2005

The prenatal diagnosis of dup(3p) was made in a female conceptus, the father being a known carrier of a balanced translocation t(3;10)(p21;q26). Interruption of pregnancy at 19 weeks showed a fetus with a holoprosencephaly field defect. Two other cases of dup(3p) have been observed in the same family. The malfor‐mations were different in each of the 3 patients, suggesting a considerable degree of variability of dup(3p).
Presymptomatic testing for Huntington chorea: Ethical and legal issues
Authors: Lamport Ann T. , Opitz John M. , Shaw Margery W.
Published: June 2005

The recently developed presymptomatic test for Huntington chorea presents ethical and legal issues relating to the interests of fiduciary and nonfiduciary third parties. The issues are examined, and the resulting dilemmas are evaluated with respect to ethical principles and to current law.
German syndrome in sibs
Authors: Lewin Susan O. , Hughes Helen E. , Opitz John M. , Reynolds James F.
Published: June 2005

We present a male‐female sib pair born to Ashkenazi Jewish parents with “arthrogryposis,” hypotonia‐hypokinesia sequence and lymphedema. Of all the “arthro‐gryposis” hypotonia syndromes, the condition in these sibs appears to be most like that of the patients of German et al [1975] and the patient of Salmon [1978]. They appear to be the first sib pair with German syndrome, which suggests autosomal recessive inheritance. Three of the four known families with affected children have been Ashkenazi Jews.
Prenatal detection of intestinal obstructions, aneuploidy syndromes, and cystic fibrosis by microvillar enzyme assays (disaccharidases, alkaline phosphatase, and glutamyltransferase) in amniotic fluid
Authors: Morin Pierre R. , Melançon Serge B. , Dallaire Louis , Potier Michel , Opitz John M. , Reynolds James F.
Published: June 2005

Microvillar enzymes (disaccharidases, alkaline phosphatase, and γ‐glutamyltrans‐ferase) were assayed in amniotic fluid from pregnancies with normal and abnormal fetuses to determine their specificity and reliability for the prenatal detection of intestinal obstructions and cystic fibrosis. All fetuses with imperforate anus, duodenal atresia, jejuno‐ileal atresia, multiple intestinal atresia, or other forms of intestinal obstructions, with or without associated ventral wall defect or aneuploidy syndrome, showed diminished microvillar enzyme activities below the normal range of control amniotic fluid samples. The exclusively intestinal hydrolases maltase, sucrase, palatinase, and alkaline phosphatase were the most reliable and sensitive markers to detect intestinal obstructions whereas more widely distributed trehalase and γ‐glutamyltransferase activities were less sensitive. The combination of intestinal disaccharidase maltase, sucrase or palatinase and ALP assays is more accurate for prenatal diagnosis of CF than a combination of intestinal ALP and GGTF assays.
The dynamics of angular homeostasis: I. General principles
Authors: Murphy Edmond A. , Berger Kenneth R. , Opitz John M.
Published: June 2005

A general model is proposed casting aspects of ontogeny in quantitative terms amenable to genetic analysis. Its primordial construct is a chain of cells (termed a “pursuer”) growing under the influence of a signal towards a fixed structure termed a “target.” There is provision for graduated correction of the direction of growth of the pursuer. The determinants of scale include the size of the cells and the distance from the target. The minimum number of parameters is two: the initial angle of growth; and the force of the correction of errors of direction. Both are potentially of genetic interest. The impact of variation in these factors on the path of growth is studied. These findings are readily translated into biological terms, notably in congenital defects of the heart. Besides the primordial purposes, there are other objectives to the process. Some membranes require free edges, or large curvatures, or circular arrays. These secondary qualities require that the cells never reach the target. The target then becomes simply a construction point: that is, while remaining a center of attraction, it is no longer a true goal. If, because of undercorrection, the cell line misses the target at the first pass, it assumes a permanent orbit about it. The orbit rapidly comes to lie on a circle, with a radius independent of the initial angle of growth but related to the cell size and the restoration constant. From this property, several kinds of structures other than a simple bridge may result, especially when a series of lines of growth together form a tissue: a cusp, a free‐floating membrane, or a circular membrane to fill a gap.
Mental retardation, deafness, skeletal abnormalities, and coarse face with full lips: Confirmation of the Fountain syndrome
Authors: Fryns Jean‐Pierre , Dereymaeker Annemie , Hoefnagels Margot , Van den Berghe Herman , Opitz John M. , Reynolds James F.
Published: June 2005

We describe 3 moderately to severely mentally retarded males (2 brothers and 1 isolated patient) with congenital deafness due to an anatomical inner ear anomaly, the same manifestations that were present in the 4 sibs reported by Fountain [1974]: skeletal abnormalities with broad, stubby hands and feet and hyperky‐phosis, and a peculiar “coarse” face with swelling of the subcutaneous tissue, particularly of cheeks and lips. According to the present observations early‐onset, generalized seizures can be added to the symptom complex of this autosomal recessive trait.
Distal arthrogryposis type II D in three generations of a Brazilian family
Authors: Pagnan Nina Amalia Brancia , Gollop Thomaz Rafael , Opitz John M. , Reynolds James F.
Published: June 2005

We report on three members of a Brazilian family with distal arthrogryposis type II D. This autosomal dominant trait was described by Hall et al [1982] and is characterized by scoliosis without associated vertebral anomalies and distal contractures.

To the best of our knowledge, this family is the second literature report of distal arthrogryposis type II D.
Aryl sulfatase A deficiency in psychiatric and neurologic patients
Authors: Herska M. , Moscovich D. G. , Kalian M. , Gottlieb D. , Bach G.
Published: June 2005

Two hundred ninety‐five psychiatric and neurologic patients were randomly screened for aryl sulfatase A (ASA) activity in lymphocyte extracts. Two of these patients showed very low ASA activity, in the range of metachromatic leukodys‐trophy (MLD)‐affected patients. The residual activity in these low ASA patients showed normal enzyme behavior with regard to ASA kinetic features and the ability to catabolize 14C labeled sulfatide by intact fibroblasts Taking into account that approximately 3% of the general population are homozygous for the pseudo‐aryl sulfatase A gene and are clinically unaffected, the data obtained here indicate that the patients studied in this work, as well as most psychiatric patients reported in the literature with low ASA activity, represent the normal ASA polymorphism. Thus, the very low ASA activity patients are in fact homozygous for the pseudo‐deficient allele, which does not result in clinical abnormalities. The clinical symptoms in these psychiatric patients and probably other “variant” MLD patients are therefore not related to low ASA activity.
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

This 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

The 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

We 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

We 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

In 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

We 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.