bluuebunny/crossref_metadata_2025 huggingface dataset:
Perrault's syndrome in two sisters
Authors: Bösze Péter , Skripeczky Katalin , Gaśl Magdolna , Tóth András , László János , Opitz John M.
Published: June 2005

We report on two sisters with Perrault's syndrome, i.e., autosomal recessive ovarian dysgenesis associated with sensorineural deafness. They were deaf‐mute and to normal height with a few minor somatic anomalies. Both had streak gonads and an apparently normal female 46,XX chromosome constitution. The parents were apparently not consanguineous. The mother had normal hearing. Other relatives were not available for study. Epilepsy, Which occurred in three relatives including one of the index patients, may have been inherited coincidentally from the mother's family.
The effects of reduced fertility, method of ascertainment, and a second unlinked locus on affected sib‐pair marker allele sharing
Authors: Risch N. , Opitz John M.
Published: June 2005

The method of affected sib‐pair marker allele sharing has been used not only for the detection of linkage, but also for discerning inheritance. The application of this method has included the tacit assumption of no selective disadvantage for affected individuals. For some of the disorders analyzed by this method, this assumption is not tenable. Also, the method of ascertainment of affected sib pairs is not taken into account. It is shown here that the ascertainement procedure and reduced reproductivity of affected individuals can alter the expected distribution of affected sib‐pair marker allele sharing. The effect is greatest for a recessive disease susceptibility locus. While the effect of reduced reproductivity is to inflate the gene frequency necessary to account for the observed distribution, a second unlinked disease susceptibility locus can diminish this effect. Application to type 1 diabetes shows that according to a simple recessive model with 50% penetrance, to observed distribution of affected sib‐pair HLA haplotype sharing requires a gene frequency in the range of 0.55–0.60, much greater than estimates previously proposed. According to such a model, the frequency of disease would be around 15%, clearly out to range of the observed frequency of 0.4%.
A familial reciprocal translocation t(3;7) (p21.1;p13) associated with the Greig polysyndactyly‐craniofacial anomalies syndrome
Authors: Tommerup Niels , Nielsen Frank , Opitz John M.
Published: June 2005

A translocation t(3;7) (p21.1;p13) segregating through four generations was found to be invariably associated with the Greig cephalopolysyndactyly syndrome (GS). High resolution chromosome analyses using G and R banding did not uncover any imbalance of the affected chromosomes, nor were the late replicating patterns changed. One girl with the GS died of a medulloblastoma.
Ring chromosome 21 in phenotypically apparently normal persons: Report of two families from Switzerland and Italy
Authors: Schmid Werner , Tenconi Romano , Baccichetti Carlo , Caufin Daniele , Schinzel Albert
Published: June 2005

If a ring 21, originating from breaks close to the telomere of 21q and anywhere in 21p, replaces a normal 21, it may be associated with an apparently normal phenotype. An apparently normal mother and son were ascertained by a prenatal chromosome study. A second mother, with a ring 21 but without gross anomalies, is short of stature, has epilepsy, and has a low normal intelligence. Her daughter is a mosaic: 46, XX/47, XX, + r(21) and has the Down's syndrome. None of these four persons was found to have mitoses with more than one ring 21 or with rings of double size.
Inbreeding studies in Brasilian schoolchildren
Authors: Freire‐Maia N. , Chautard‐Freire‐Maia E. A. , de Aguiar‐Wolter Iêda P. , Azevedo‐Fialho Maria da Graça , de Azevedo M. Barros , Krieger H. , Barbosa C. A. A. , Freire‐Maia N. , Chautard‐Freire‐Maia E. A. , Barbosa C. A. A. , Krieger H. , Cat I. , Marinoni Leide P. , Giraldi D. J. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Cat I. , Giraldi D. J. , Marinoni Leide P. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Müller Valderez S. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Monte‐Serrat Ísis S. , Freire‐Maia N. , Chautard‐Freire‐Maia E. A. , Kreiger H. , Barbosa C. A. A.
Published: June 2005

We present results of comparisons between consanguineous and control couples and their children in Southern Brasil. Multiple regression, t‐test and χ2 analyses were applied to the data. The following variables were investigated; Parents: structure of first cousin marriages, latitude and longitude of birthplaces, cohabitation time, rurality, marriage age, occupation, number of liveborn children, and frequency of twinning. Schoolchildren: clinical data as classified into 24 discontinuous traits, each one subdivided into two categories (number and severity), and seven continuous traits (weight, height, pulse rate, respiratory rate, systolic pressure, diastolic pressure, and temperature); nutrition indices and biotype; family names; intelligence tests and school performances; birth order, age, hair color, hair type, eye color, and skin color; twinning in the sibship, and infant mortality among sibs of the propositi.

Our study showed a) nonrandomness of consanguineous marriages as detected on structural, racial, geographical, and temporal levels; b) a heavy mutational load of about 1.5 lethons acting on infant mortality; c) no inbreeding effect on morbidity in general (with a possible exception of “ear morbidity”, including hearing deficit); d) a modest inbreeding depression on height (a decrease of 2 cm with an increase of 10% of inbreeding); e) a suggestion of inbreeding depression on “intelligence”.
Creatine‐kinase (CK) and pyruvate‐kinase (PK) activities in cord blood of normal newborn infants: Application to duchenne muscular dystrophy screening programs
Authors: Passos Maria Rita , Zatz Mayana
Published: June 2005

Creatine‐kinase (CK) and pyruvate‐kinase (PK) were determined in cord blood samples from 125 normal newborn infants in order 1) to investigate the correlation between CK and PK, 2) to evaluate a possible influence of the mode of delivery (cesarean section versus vaginal delivery) and birth weight on enzyme activity, 3) to establish normal values for both sexes. In the present investigation, the enzyme activities of cord blood were significantly higher than in the normal adult, and no correlation was observed between enzyme activity and mode of delivery or birthweight.

Although there was an apparent and significant correlation (r = 0.5) between CK and PK levels in cord blood samples, in no case did we find both high CK and PK values, something that would suggest preclinical DMD or a false‐positive result.

These results have led us to suggest determination of serum PK activity in male newborn screening programs. This would allow an early discrimination between false‐positives and preclinical cases already in the neonatal period. Furthermore, the concomitant use of PK and CK in boys not walking by 18 months could be a useful test for diagnosing preclinical DMD boys.
A new X‐linked mental retardation‐overgrowth syndrome
Authors: Golabi Mahin , Rosen Linda , Opitz John M.
Published: June 2005

We report on a family with 4 affected males in 3 generations with a previously unreported X‐linked mental retardation/multiple congenital anomaly (XLMR/MCA) syndrome. The propositus was a 7‐year‐old Latin American moderately retarded male with; prenatal and postnatal overgrowth; short, broad upturned nose; large mouth; midline groove of tongue, lower alveolar ridge and lower lip; submucous cleft palate; supernumerary nipples; 13 ribs; Meckel's diverticulum; intestinal malrotation; coccygeal skin tag and bony appendage; hypoplastic index fingernails; postaxial polydactyly of the right hand, bilateral syndactyly of 2nd and 3rd fingers; and tibial clinodactyly of 2nd toes. His sister's son, a premature infant who died at 4 months, had nearly identical manifestations. The propositus and his nephew had normal chromosomes. A brother and son of the sister of the mother of the propositus were similarly affected and both died in the newborn period. The mother of the propositus had a large mouth, coccygeal skin tag and bony appendage, and hypoplastic index fingernails.

This distinct mental retardation/multiple congenital anomaly syndrome is added to the growing list of presently known X‐linked MCA/MR syndromes.
A new X‐linked multiple congenital anomalies/ mental retardation syndrome
Authors: Golabi Mahin , Ito Melani , Hall Bryan D. , Opitz John M.
Published: June 2005

We report on 2 boys, the sons of sisters, and their mother's brother who have a new, X‐linked multiple congenital anomalies/mental retardation (MCA/MR) syndrome. The propositus was a 16‐month‐old caucasian male with 1)mental retardation, 2) congenital microcephaly, 3)postnatal growth deficiency, 4)ridged metopic suture with narrow bifrontal diameter, 5)upslanted palpebral fissures with persistent epicanthal folds, strabismus, and lacrimal duct obstruction, 6)narrow palate, 7)macrodontia, 8)anteverted ears, 9)atrial septal defect, 10)dry brittle scalp hair and 11)cutis marmorata. His chromosomes were normal. His cousin and uncle were similarly affected. This distinctive MCA/MR syndrome is added to the list of X‐linked malformation syndromes known at the present time.
Osteogenesis imperfecta type II delineation of the phenotype with reference to genetic heterogeneity
Authors: Sillence D. O. , Barlow K. K. , Garber A. P. , Hall J. G. , Rimoin D. L.
Published: June 2005

A group of fetuses with a perinatally lethal variety of osteogenesis imperfecta (O.I. type II) is charaterized by short limbs, and clinical and roentgenological evidence of severe osseous fragility and defective ossification. Forty‐eight cases were reviewed and can be subdivided into 3 groups on the basis of small but probably significant differences in clinical and radiographic findings. Group A (38 cases): short, broad, “crumpled” long bones, angulation of tibiae and continuously beaded ribs. Group B (6 cases): short, broad, crumpled femora, angulation of tibiae but normal ribs or ribs with incomplete beading. Group C (4 cases): long, thin, inadequately modelled, rectangular long bones with multiple fractures and thin beaded ribs. Consistency of findings within sibships suggests the groups reflect genetic heterogeneity.

An increased frequency of parental consanguinity, sib occurrence with normal parents, and normal mean paternal age at birth, suggest that most cases of O.I. type II represent autosomal recessive traits.

Some previously reported cases and the biochemical findings in one case suggest still further genetic heterogeneity.
Familial congenital diaphragmatic defects: Aspects of etiology, prenatal diagnosis, and treatment
Authors: Norio Reijo , Kääriäinen Helena , Rapola Juhani , Herva Ritta , Kekomäki Martti
Published: June 2005

We present 14 familial cases from five Finnish families affected with a life‐threatening congenital diaphragmatic defect (CDD) and review data on 53 previously published familial cases. CDD occurred in three sibs and their half brother's son, and probably in all four offspring of parents consanguineous as both first and second cousins. In the remaining three Finnish families and in the vast majority of the previously reported familial cases, only two sibs were affected. Two thirds of those affected were males both in the Finnish and the overall series.

Pedigree data, delayed fusion of the diaphragm as the primary pathogenetic mechanism, varying anatomical structure of the defective hemidiaphragm, association with other congenital anomalies, and data on animal experiments are more in accordance with multifactorial determination than with recessive inheritance. This does not exclude other genetic causes in some familial cases.

The recurrence risk for sibs after one affected sib is about 2%. As the prognosis, especially in familial cases of CDD has remained grave, the development of fetal surgical treatment is desirable. This emphasizes the future role of prenatal diagnosis by ultrasound.
Duplication of distal 17q: Report of an observation
Authors: Naccache Nadyr F. , Vianna‐Morgante Angela M. , Richieri‐Costa A. , Opitz John M.
Published: June 2005

We describe a boy with the syndrome due to dup(17q) resulting from a paternal balanced t(12;17) (q24;q23). The comparison of the clinical findings in our patient with those previously reported shows that the dup(17q23 → qter) is associated with a clinically recognizable syndrome. Anomalies present in ≥ 75% of the patients were severe psychomotor retardation; short stature; microcephaly; frontal bossing and temporal retraction; widow's peak; narrow palpebral fissures; flat nasal bridge; thin upper lip overlapping thin lower lip; downturned corners of the mouth; apparently low‐set, posteriorly angulated and malformed ears; low posterior hairline; widely spaced nipples; cryptorchidism; proximal limb shortness; and hyperlaxity of limb joints.

The translocation carrier father of our patient had a Poland anomaly.
Heterozygote detection in hunter syndrome
Authors: Zlotogora Joël , Bach Gideon
Published: June 2005

Iduronate sulfate sulfatase activity was determined in 36 women, relatives of Hunter syndrome patients. The use of serum and lymphocyte extracts for the determination of enzyme levels enabled the detection of 13 out of 15 (86%) obligate heterozygotes and identification of 10 of 21 other relatives as carriers. These methods are relatively simple and can easily be applied for routine examinations of all women at risk of being a Hunter heterozygote. These results permit for the first time meaningful genetic counseling for the families of Hunter patients.
Prune belly syndrome: Observations supporting the hypothesis of abdominal overdistention
Authors: Burton Barbara K. , Dillard Robert G. , Opitz John M.
Published: June 2005

We report on an infant with the prune belly syndrome who was unusual in that the typical manifestations of the disorder were accompanied by an anterior abdominal wall defect. We speculate that this defect may have occurred as a result of splitting of the abdominal wall secondary to massive bladder dilatation and stretching of the abdominal muscles. An alternative explanation is that the defect may have been the result of secondary pressure necrosis from stretching forces or from contact with another structure, such as the cervix. This case lends further support to the hypothesis that bladder distention with overdistention of the abdomen may be the primary event leading to the findings observed in the prune belly syndrome.
Linkage analysis in a large kindred with autosomal dominant transmission of polyglandular autoimmune disease type II (Schmidt syndrome)
Authors: Butler Merlin G. , Hodes M. E. , Conneally P. M. , Biegel Angenieta A. , Wright James C. , Opitz John M.
Published: June 2005

Schmidt syndrome (PGA syndrome type II) is a rare condition characterized by polyglandular failure. It is an autosomal dominant trait with variable expressivity that was inherited over four generations in an Indiana kindred. Association of HLA‐B8 has been reported with Schmidt syndrome. Our proband is a 12‐year‐old boy with Addison disease, insulin dependent diabetes mellitus (IDDM), and vitiligo. Two of his eight sibs had either IDDM (sister) or vitiligo and hyperthyroidism (brother). His mother had hypothyroidism. Seven members of earlier generations apparently were also affected. We obtained peripheral blood for HLA and genetic analysis from 21 relatives in a family with 8 Schmidt syndrome individuals in three generations. HLA studies on 15 affected and unaffected relatives showed only 2 of 7 persons with B8‐containing haplotypes. Therefore, no association exists between the B8‐containing haplotype and the syndrome.

We identified informative marker loci. No evidence for linkage of the Schmidt locus to any of the 14 markers was found and close linkage to esterase D and adenylate kinase and possibly properdin factor B was excluded.
Genetic counseling and reproductive uncertainty
Authors: Wertz Dorothy C. , Sorenson James R. , Heeren Timothy C. , Opitz John M.
Published: June 2005

Of 836 fertile women seeking genetic counseling, 544 (65%) reported that their major reason for doing so was to obtain information to help in deciding if they should have a child. Thirty‐four percent of these 836 women entered counseling uncertain about undertaking a pregnancy in the next 2 years. After counseling, 28% of the 836 had uncertain pregnancy intentions. These included 66% of those who were uncertain and 11 % of those who were reproductively certain before counseling. Stepwise logistic regression identified the following as independently and significantly associated with reproductive uncertainty after counseling: 1) uncertainty before counseling; 2) uncertainty about ideal family size; 3) concern about the effects of an affected child on the client's social life; 4) perceived serious problems caring for a child with a birth defect now living at home; and 5) new concerns raised in counseling. Reproductive uncertainty after counseling was not related to characteristics of the risked birth defect, level of risk, treatment potential, or client learning of medical and genetic facts. These data suggest that genetic counseling will not eliminate reproductive uncertainty for many clients, because this uncertainty is related to factors mainly outside the usual scope of counseling.
Factors related to subsequent reproductive outcome in couples with repeated pregnancy loss
Authors: Fitzsimmons Jack , Tunis Sandra , Jackson Douglas , Wapner Ronald J. , Jackson Laird
Published: June 2005

Specific factors in a couple's history may influence the recurrence risk following repeated pregnancy loss (RPL). Couples with RPL were contacted several years following evaluation and information concerning subsequent pregnancies was obtained. Linear regression analysis was utilized to determine which factors in the history were significant predictors of pregnancy outcome following evaluation. A family history of RPL or a “genetic defect” was a highly significant predictor of subsequent unsuccessful pregnancies. Surgical, but not medical, treatment for RPL was a significant predictor of eventual successful outcome. The number of abortions prior to evaluation for RPL, presence of a liveborn child, maternal age at evaluation, and intercurrent infertility all failed to be significant predictors of pregnancy outcome after evaluation.
One hundred twin pregnancies in a prenatal diagnosis program
Authors: Taylor Maida B. , Anderson Robert L. , Golbus Mitchell S. , Opitz John M.
Published: June 2005

One hundred pairs of twins were encountered in 8,500 pregnancies having genetic amniocentesis. Only 5 of 27 (18.5%) pairs were recognized before the institution of routine ultrasonic examination, while 69 of 73 (94%) twin pairs were found after ultrasound use. Amniotic fluid was obtained from both sacs in 71 of the 73 (97%) identified twin gestations in which both twins were living at the time of amniocentesis.
Familial neonatal and infantile seizures: An autosomal‐dominant disorder
Authors: Zonana Jonathan , Silvey Kerry , Strimling Bruce
Published: June 2005

Familial neonatal seizures are an important and probably underrecognized disorder. A family with six affected individuals in three generations was evaluted and their clinical characteristics were compared with those of 15 families previously reported in the literature. An analysis of the 116 affected individuals uncovered a typeical clinical picture of onset of seizures by 2 to 8 days of life in an otherwise healthy appearing infant, and cessation of seizures by 1 to 6 months. Results of diagnostic evaluations were normal, and the pathogenesis of the disorder is still unclear. Long‐term neurodevelopmental outcome was normal except for an increased rate (11%) of subsequent seizures in childhood or as an adult. The disorder was inherited as an autosomal‐dominant trait with a high degree of penetrance.
Some questions on the significance of chromosome alterations in leukemias and lymphomas: A review
Authors: Neri Giovanni , Opitz John M.
Published: June 2005

Recent improvement in the methods of chromosome analysis has allowed recognition of consistent chromosome alterations in several human cancers, especially leukemias and lymphomas. At the same time, newly discovered human cellular oncogenes have been mapped to individual chromosomes, with precise band assignment. Some of the assignments are coincident with the breakpoints of translocations observed in particular tumors. In fact, a relocation of the corresponding oncogenes has been observed in the cells of some of these tumors. Two notable examples are that of the t(9;22) translocation of chronic myelogenous leukemia (CML), causing the transfer of the oncogene c‐abl from chromosome 9 to chromosome 22, and that of the t(8;14) translocation of Burkitt lymphoma, causing the transfer of the oncogene c‐myc from chromosome 8 to chromosome 14. These findings can be taken as indicative of a critical role of chromosome alterations in the origin of cancer, through the activation of one or more cellular oncogenes, although there is no firm evidence that such an activation actually occurs. In addition, some concern exists over the validity of accepting in vitro transformation of a cell line by oncogenes as a model of carcinogenesis in man. For these reasons the question on the significance of chromosome alterations in leukemias and lymphomas should not be considered entirely settled yet. Useful models, whose study may lead to the clarification of this important point, are represented by premalignant conditions, such as the myeloproliferative disorders, where chromosome abnormalities are present before the development of a bona fide neoplasm, and by the aneuploidy syndromes, in which there exists an association between a constitutional chromosome anomaly and an increased risk of cancer.
Gross anatomical studies of a newborn infant with the Meckel syndrome
Authors: Pettersen James C. , Opitz John M. , Reynolds James F.
Published: June 2005

A male infant with the Meckel syndrome was studied anatomically. The findings were compared to those from eight trisomy 13 cases to determine whether or not the superficial similarities between the two syndromes were matched by similarities in the internal variations. Emphasis was on the head and limbs. In the head, major differences were found in the nasal bones, mandible, and tongue. In the limbs, the skeletal variations were more severe in the Meckel syndrome infant, but he lacked the muscle variations diagnostic of trisomy 13.
Genetic counseling in Becker type X‐linked muscular dystrophy. II: Practical considerations
Authors: Grimm T.
Published: June 2005

A frequent problem of genetic counseling in Becker muscular dystrophy (BMD) is the differential diagnosis between BMD and the autosomal recessive benign limb‐girdle muscular dystrophy (LGMD) if the pedigree pattern is not typical of X‐linkage. In this situation, the a priori probability that a woman and her husband may be heterozygotes for LGMD can be shown to be 80μ/a (μ = mutation rate in BMD: a = incidence ratio between BMD and LGMD). In addition, the agecorrected serum creatine kinase (CK) values of all female relatives are also important for the risk calculation of a woman being carrier of BMD.
On the statistical determination of major gene mechanisms in continuous human traits: Regressive models
Authors: Bonney George Ebow , Opitz John M. , Reynolds James F.
Published: June 2005

We consider the analysis of a continuous trait measured on human families and pedigrees to elucidate the mechanism of underlying major genes. Thinking in terms of the naturally Markovian structure of the dependencies in pedigrees rather than variance components, we describe natural classes of regressive models that are computationally feasible. These models can accommodate wide generalizations of the residual variation, and so should provide a stronger basis than other models. proposed to date for inferring the segregation and linkage relationships of major genes.
A prenatally detected inv dup(15)
Authors: Pecile Vanna , Archidiacono Nicoletta , Rustico Maria Angela , Fiscella Claudio , Rocchi Mariano , Opitz John M. , Reynolds James F.
Published: June 2005

An extra G group‐like chromosome was found in an amniotic fluid cell culture. With multiple banding techniques it was identified as inv dup(15). BUdR incorporation was used to determine the lateral asymmetry of the marker, which consisted of 2 distal spots arranged contralaterally, consistent with DNA polarity conservation in chromosome rearrangements.
Pulmonary arteriovenous malformations related to Rendu‐Osler‐Weber syndrome
Authors: McCue Carolyn M. , Hartenberg Michael , Nance Walter E.
Published: June 2005

Interest in Rendu‐Osler‐Weber (ROW) syndrome has been renewed because of new treatment for the pulmonary artery fistulae that occur in approximately one‐half of the patients. Pulmonary arteriovenous malformations (AVM) can be occluded safely by the transvenous placement of a silicone balloon thus avoiding the many potential complications of thoracotomy. Thirty‐three members of four generations of a family with ROW illustrate the varied manifestations of the syndrome and provide a basis for review of clinical findings and therapeutic approaches to the management of pulmonary AVMs during the last 25 years. Special attention is given to early detection and prevention of major complications. Since ROW syndrome is an inherited trait, informed genetic counseling is an important component of the overall management of families with this disorder.
Tetraploidy: A report of three live‐born infants
Authors: Scarbrough Paula R. , Hersh Joseph , Kukolich Mary K. , Carroll Andrew J. , Finley Sara C. , Hochberger Richard , Wilkerson Shirley , Yen F. F. , Althaus Becky W.
Published: June 2005

We present three live‐born infants with tetraploidy and compare them with two previously reported live‐born infants with the same genetic defect. Common anomalies noted included microcephaly; a prominent, narrow forehead; microphthalmia/anophthalmia; cleft palate; orthopedic anomalies; genital ambiguity; and abnormalities of the central nervous system, including pituitary hypoplasia. Together these constitute a rather characteristic phenotype. An error in cytoplasmic cleavage is theorized to be a mechanism for the chromosome anomaly and is supported by the presence of parental polymorphisms in one of our cases; however, the presence of a small percentage of tetraploid cells in the leukocytes and skin fibroblasts of this patien's mother does not exclude maternal mosaicism as the basis for polyploidy in certain instances.
Determination for different severity of anemia in thalassemia: Concordance and discordance among sib pairs
Authors: Fucharoen Suthat , Winichagoon Pranee , Pootrakul Pensri , Wasi Prawase
Published: June 2005

The degree of anemia in β°‐thalassemia/hemoglobin E disease is highly variable. As part of an attempt to identify determinants of this variability of severity we studied concordance and discordance of hemoglobin levels among sib pairs. The distribution of differences of hemoglobin levels in 216 sib pairs from 98 families showed a remarkable skewness toward the lower values with a mode at 0‐0.5 gm/dl. The prevailing concordance of hemoglobin levels in patients from the same families and the persistence of the patterns indicate that polygenic factors are mainly responsible for the variability of anemia in this disease.
Age structure and the distribution of rare genetic diseases
Authors: Yokoyama Shozo , Ward Richard H.
Published: June 2005

Equilibrium frequencies of rare deleterious genes in an age‐structured population have been studied by using mathematical models. In the models, variable age‐of‐onset and variable penetrance of a trait have been incorporated. Numerical analyses show that the equilibrium gene frequencies can be approximated extremely well to those in nonoverlapping generations, as Haldane [1927] claimed. This property of rare deleterious genes in an age‐structured population is important because population dynamics of such genes in a finite population can be studied easily.
Multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to interstitial deletion 1q
Authors: Steinbach P. , Wolf M. , Schmidt H.
Published: June 2005

A severely retarded male infant was found to have a previously undescribed multiple congenital anomalies/mental retardation (MCA/MR) syndrome including microdolichocephaly, prominence of metopic suture, coarse scalp hair, epicanthus, anteverted nostrils, micrognathia, posteriorly angulated malformed auricles, preaxial hexadactyly, clinodactyly, camptodactyly, hypospadias, cryptorchidism, inguinal hernias, agenesis of left kidney, and pyloric stenosis. This syndrome was due to an interstital del(1)(q25.2q31.2) associated with a paracentric inv(1)(q31.2q44).
Namaqualand hip dysplasia: An autosomal dominant entity
Authors: Beighton Peter , Christy Gail , Learmonth I. D.
Published: June 2005

A unique inherited skeletal disorder has been identified in 45 persons in five generations of a kindred of mixed ancestry in South Africa. Discomfort in the hip joints develops in childhood and the course is progressive, with handicap in middle age. General health is good, height is not reduced by any significant degree, and there is no nonskeletal involvement. The major changes are in the femoral capital epiphyses, which are flattened and fragmented; secondary degenerative arthropathy develops at a later stage. Platyspondyly of variable but mild degree is present in about 60% of affected persons. Other minor changes, including iliac exostoses, are present occasionally.

Pedigree data indicate autosomal dominant inheritance, with a reasonably consistent phenotypic expression. In view of the geographic distribution of this condition we propose the designation “Namaqualand hip dysplasia” (NHD).
Testicular regression in a patient with virilized female phenotype
Authors: Rosenberg Carla , Mustacchi Z. , Braz A. , Arnhold I. J. P. , Chu T. H. , Carnevale J. , Frota‐Pessoa O.
Published: June 2005

The 16‐year old girl studied here had ambiguous external genitalia, ie, enlarged clitoris, pseudo vagina, and rudiments of Wolffian tubes. Her karyotype was 46, XY and she was H‐Y antigen‐positive. In spite of absence of gonadal tissue, genital virilization suggests presence of testes during embryogenesis. This patient is compared to 20 others with testicular regression from the literature. Autosomal‐recessive inheritance of this condition is proposed.
Growth retardation, Alopecia, Pseudo‐anodontia, and optic atrophy—The GAPO syndrome: Report of a patient and review of the literature
Authors: Tipton Robert E. , Gorlin Robert J.
Published: June 2005

The GAPO syndrome is a rare but distinct autosomal‐recessive disorder. The term GAPO is an acronym for the manifestations of Growth retardation, Alopecia, Pseudo‐anodontia (failure of tooth eruption), and progressive Optic atrophy. We are aware of five other published patients. All have a strikingly similar appearance. This, along with other distinct manifestations, should allow clear differentiation from other causes of growth retardation. The hypothesis of autosomal‐recessive inheritance is based on parental consanguinity and affected sibs in several cases.
Macrocephaly with hamartomas: Bannayan‐Zonana syndrome
Authors: Miles Judith H. , Zonana Jonathan , Mcfarlane Jean , Aleck Kirk A. , Bawle Erawati
Published: June 2005

Familial macrocephaly with mesodermal hamartomas is described as a distinct syndrome in nine individuals from four families. Constant manifestations include symmetrical macrocephaly without ventricular enlargement, mild neurological dysfunction, and postnatal growth deceleration. Speech and motor delays observed in all the children were usually well compensated by adulthood. Two children had mild mental retardation and seizures which may have been related to intracerebral hemorrhage in one. Mesodermal hamartomas were present in affected persons from all four families, with 60% of individuals manifesting only discrete lipomas and hemangiomas. More serious tumors, including intracerebral hemangiomas, hemangiomatous involvement of the bone, and aggressive lipomas occurred in 40%. Other findings that make it possible to delineate a recognizable syndrome include down‐slanting palpebral fissures (66%), a high palate (67%), joint hyperextensibility (55%), pectus excavatum (22%), strabismus or amblyopia (33%), and prolonged drooling (44%). The Bannayan‐Zonana syndrome is an autosomal‐dominant trait with male predominance of affected individuals.
Achondroplasia: Unexpected familial recurrence
Authors: Reiser Catherine A. , Pauli Richard M. , Hall Judith G.
Published: June 2005

We review six families in which recurrence of achondroplasia, inexplicable through autosomal dominant inheritance, has occurred. The clinical and radiographic characteristics of affected individuals in these families are identical to those usually seen in achondroplasia. Family histories and parental characteristics likewise seemed not to set this group apart from others with achondroplasia. While various mechanisms for these occurrences of achondroplasia in family members related through unaffected relatives can be postulated, the hypothesis that these recurrences were simply the result of two independent chance events cannot, at least for the moment, be excluded.
Mental retardation, unusual face, and intrauterine growth retardation: A new recessive syndrome?
Authors: Pitt D. B. , Rogers J. G. , Danks D. M.
Published: June 2005

We describe two mentally retarded sisters with intrauterine growth retardation and subsequent dwarfism and an unusal and characteristic face together with two other unrelated patients with similar manifestations. These four patients may represent a new autosomal recessive syndrome.
Effects of selection for serum cholesterol concentrations on serum lipid concentrations and body weight in baboons
Authors: Kammerer Candace M. , Mott Glen E. , Carey K. Dee , McGill, Henry C.
Published: June 2005

We examined the results of one generation of selection for serum cholesterol (SC) concentration on low density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C), and triglyceride concentrations and weight in baboons (Papio cynocephalus). Parents of two lines (high SC response and low SC response) were chosen based on their SC response to a 4‐month challenge with a cholesterol and saturated fat enriched diet. Parents of the control line were chosen without regard for SC levels. Expression of SC, LDL‐C, and HDL‐C concentrations was moderately influenced by additive genetic effects as evidenced by the direct and correlated responses of the serum lipoprotein concentrations of the juvenile offspring of the three lines. Realized heritability of SC and genetic correlations of SC with LDL‐C and HDL‐C were moderate to high. Sex and age were important factors influencing expression of SC, LDL‐C, HDL‐C, trigylcerides, and weight in both adult baboons and their offspring.
Prenatal diagnosis and fetal pathology of aspartylglucosaminuria
Authors: Aula Pertti , Rapola Juhani , von Koskull Harriet , Ämmälä Pirkko
Published: June 2005

The prenatal diagnosis of aspartylglucosaminuria (AGU), a lysosomal storage disorder of glycoprotein degradation, was made by demonstrating the deficiency of N‐aspartylgucosaminidase on cultured cells from a midterm amniotic fluid sample. Four other amniotic fluid studies from at‐risk pregnancies gave a normal or a heterozygote level of enzyme activity. These pregnancies have gone to term and the delivery of healthy babies. The pregnancy with the affected fetus was terminated and the prenatal diagnosis was verified by enzyme assays on cord blood lymphocytes, cultured cells from skin biopsy, and from placental villi. Electron microscopic evidence of lysosomal storage was seen in several organs of the fetus with the notable exception of the central nervous system. The undifferentiated mesenchymal fibroblasts particularly were heavily loaded with cytoplasmic inclusions in skin, liver, kidney, and placenta.
FG syndrome in a premature male
Authors: Bianchi Dian W.
Published: June 2005

A 30‐week premature male infant is presented with dolichocephaly, frontal bossing, down‐slanting palpebral fissures, hypertelorism, long philtrum, micrognathia, cleft palate, and imperforate anus. He is the fifth patient to be presented with FG syndrome and sensorineural deafness. The patient's syndromic manifestations became more obvious during an inpatient observation period of 3 months.
Homozygous NADH‐methemoglobin reductase and aspartylglucosaminidase deficiencies in a moderately retarded sicilian child
Authors: Musumeci S. , Salvati A. , Schiliró G. , Salvo G. , Di Dio R. , Caprari P.
Published: June 2005

We report on a 10‐year‐old boy with generalized deficiency of both NADH‐methemoglobin reductase and aspartylglucosaminidase. Althoug the two enzymatic defects, both autosomal recessive traits, are associated with severe mental retardation, the patient was less retarded than his sister who had only aspartyl‐glucosaminuria.
Are the occasional aneuploid cells in peripheral blood cultures significant?
Authors: Wenger Sharon L. , Golden Wendy L. , Dennis Suzanne P. , Steele Mark W.
Published: June 2005

Cytogenetic results of 1,500 consecutive clinical cases from a young population were analyzed for rare cells with hypermodality (≥ 47 chromosomes) or hypomodality (≤ 45 chromosomes). Such instances of non‐modal chromosome gains or losses were random relative to referral diagnosis or modal karyotype. However, chromosome loss was correlated with size, smaller chromosomes being lost more frequently (correlation coefficient = 0.794). Sex chromosome gain or loss in vitro was of particular interest since mosaicism in vivo is frequently found in patients presenting with manifestations of Turner or Klinefelter syndrome. Cases with a referral diagnosis of sex chromosome abnormality showed no increased gain or loss of an X or Y chromosome when compared to other types of clinical cases. Our analyses suggest that when one non‐modal cell is found with a gain or loss of a chromosome relevant to the referral diagnosis, then the results on a count of 40 cells should differentiate in vitro artifact from probable in vivo mosaicism with 95% degree of confidence.
Rh immune globulin after genetic amniocentesis: Impact on pregnancy outcome
Authors: Crane James P. , Rohland Barbara , Larson Dale
Published: June 2005

Although Rh immune globulin is commonly given to Rh‐negative women undergoing genetic amniocentesis, there is little documentation of the necessity, efficacy, or safety of this policy. In this study, reproductive outcomes in 147 women each receiving 150 μg of Rh immune globulin after genetic amniocentesis were compared with those of an equal number of Rh‐positive amniocentesis control women. No significant differences were found in the incidence of midtrimester pregnancy loss, mean gestational age at delivery, mean birth weight, or frequency of preterm deliveries (P > 0.05 for all parameters). While two antepartum stillbirths occurred in the study group and none in the control population, causes unrelated to Rh immune globulin administration were apparent for both fetal deaths (one multiple congenital anomaly syndrome, one abruptio placentae at 38 weeks). Of the 103 Rh‐negative women giving birth to Rh‐positive infants, none were overtly sensitized at the time of delivery. It is concluded that second trimester Rh immune globulin administration does not increase the risk of pregnancy loss.
Introduction to the study of pre‐and postnatal growth in humans: A review
Authors: Mendez Heirie , Opitz John M. , Reynolds James F.
Published: June 2005

This review is divided in several items. A brief introduction on the characterization of the growth processes is made; the ways of assessing fetal development and well‐being, the factors acting on fetal growth and birth weight, the causes and post‐natal consequences of prematurity and intrauterine growth retardation are discussed in the first part. The following items deal mainly with: the normal pattern of growth from birth to puberty according to sex, race, and nutritional status, with special mention to pubertal changes; methods for predicting adult height from skeletal age; the effect of hormones during pre‐ and post‐natal life; and the genetics of adult stature.

The remainder of this review deals with genetic causes of growth abnormalities. Constitutional delay of growth, familial short stature, hypothalamic‐pituitary dwarfism, skeletal dysplasias and many genetic syndromes presenting intrauterine growth retardation are listed. Aneuploidy effects on human growth are extensively reviewed, and usual growth patterns in Down and Ullrich‐Turner syndrome patients as well as other sex aneuploid individuals and mosaics are fully described. The influences of X and Y chromosomes on growth and maturation are also discussed. Finally, some remarks are made about overgrowth syndromes.
Tandem duplication of proximal 22q: A cause of cat‐eye syndrome
Authors: Reiss Jacob A. , Weleber Richard G. , Brown Michael G. , Bangs Charles D. , Lovrien Everett W. , Magenis R. Ellen , Opitz John M. , Reynolds James F.
Published: June 2005

A boy with bilateral colobomas, preauricular pits, and developmental delay had a 46, XY, 22q + karyotype. His parents had normal chromosomes. The abnormality of 22q was interpreted as a de novo tandem duplication of 22q11.1 → q11.2. Although no anal abnormality was identified, his manifestations are otherwise consistent with those of the cat‐eye syndrome. Blood marker results and the levels of galactosidase‐2, galactosidase‐B and arylsulfatase‐A, which are known to be coded on 22q, are normal.
De novo 21q interstitial deletion in a retarded boy with ulno‐fibular dysostosis
Authors: Reynolds James F. , Wyandt Herman E. , Kelly Thaddeus E. , Opitz John M. , Reynolds James F.
Published: June 2005

A 9‐year‐old boy was referred for evaluation of multiple anomalies and mental retardation. Skeletal abnormalities had been noted at birth: joint contractures, right acetabular “dysplasia,” ulno‐fibular dysostosis, and bilateral talipes equinovarus with calcaneocuboid fusion. Additional findings at 9 years included short stature, unusual facial appearance, camptodactyly of several digits, undescended testes, and syndactyly of toes 4 and 5. On psychological testing he was found to be moderately retarded. Cytogenetic analysis of chromosome bands using Q, GTG, R, and C banding showed an interstitial deletion of 21q; karyotype designation: 46, XY, del (21) (pter→q11.2::q22.1→qter). Parental chromosomes were normal. Manifestations in this boy, including the joint contractures, are similar to those described in the monosomy 21 syndrome. Ulno‐fibular dysostosis has not been reported previously with abnormalities of chromosome 21. To our knowledge, this is the second patient reported with an interstitial deletion of chromosome 21, and the patients are phenotypically dissimilar.
Paternity testing. 2: Likelihood ratio tests
Authors: Kaiser L. , Seber G. A. F.
Published: June 2005

It is known that the so‐called paternity index is also a likelihood ratio statistic for testing that an alleged father is the true father. Unfortunately the likelihood ratio test can sometimes lead to unsatisfactory results because of its dependence on the phenotype combinations of the mother and child. A new, conditional likelihood ratio test, which we call the ancillary test, is proposed in which statistical testing is carried out conditionally on the phenotypes of the mother and alleged father. An exact procedure is available which can be executed with reasonable facility on a microcomputer.
Transmitting balanced translocation carrier information within families: A follow‐up study
Authors: Suslak Lorraine , Price David M. , Desposito Franklin , Opitz John M. , Reynolds James F.
Published: June 2005

Approximately 1 of 500 individuals is a carrier of a balanced chromosome translocation. Since many translocations are inherited, many (but not all) relatives of carriers have a need to be informed of their potential carrier status. Presently, no data are available as to what extent individuals identified as balanced carriers inform at‐risk relatives of the problem.

We interviewed 12 balanced translocation carriers to learn whether such information had been transmitted to relatives. The 12 propositi had 36 surviving sibs and 21 surviving parents. Of the 36 sibs, 32 were informed of their risk. The four sibs not informed were from two families. Only 16 of the 32 informed sibs had subsequent carrier testing. Of the 21 surviving parents, 14 were told by their children of their carrier status; subsequently, three parent couples were tested.

This survey provides data showing that individuals do not always discolose genetic risk information to relatives. Therefore, genetic professionals need to determine if they have a duty to transmit such information to at‐risk relatives in light of the harm that may occur when informatin is withheld.
Syndrome of amelogenesis imperfecta, nephrocalcinosis, impaired renal concentration, and possible abnormality of calcium metabolism
Authors: Lubinsky Mark , Angle Carol , Marsh P. Wayne , Witkop C. J. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a brother and sister with amelogenesis imperfecta, nephrocalcinosis and impaired renal concentrating ability. This is the second sibship reported, further substantiating autosomal recessive inheritance of this condition. There is lack of enamel, lifelong nocturnal enuresis, progressive punctate nephrocalcinosis, and decreased calcium and phosphate excretion over 24 hours and after an acute load. Increased serum osteocalcin and decreased urine δ‐carboxiglutamic acid suggest involvement of vitamin K‐dependent calcium binding proteins, although this may represent a secondary finding. No other evidence of abnormal calcium metabolism was found. Renal function is stable in the early teens, but the previously reported patients went on to renal failure.
Oto‐palato‐digital syndrome, type II—an X‐linked skeletal dysplasia
Authors: Brewster Thomas G. , Lachman Ralph S. , Kushner David C. , Holmes Lewis B. , Isler Robert J. , Rimoin David L. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on two male infants with a lethal skeletal dysplasia characterized by cleft palate, midface hypoplasia, downward‐slanting palpebral fissures, small thorax, and bowed limbs with absent fibulae. The clinical and radiographic changes are similar to those seen in the recently proposed oto‐palato‐digital syndrome, type II [Fitch et al, 1983]. The disorder is X‐linked with heterozygous females being more mildly affected.
Deletions of proximal 15q and non‐classical Prader‐Willi syndrome phenotypes
Authors: Schwartz S. , Max S. R. , Panny S. R. , Cohen M. M. , Optiz John M. , Reynolds James F.
Published: June 2005

A deletion of the long arm of chromosome 15 (usually involving bands 15q 11‐q12) has been seen in approximately 50% of Prader‐Willi syndrome (PWS) patients [Ledbetter et al, 1982]. However, 14 patients with non‐PWS (or atypical PWS) phenotype with 15q deletion indicate great clinical variability. A deletion was found in a propositus with a de novo translocation [45, XY,−15, −22, +rec(15;22)(22pter → 22q13.2::15q14 → 15qter)], who had anomalies not normally observed in PWS patients. Activities of several enzymes mapped to the involved chromosomes were studied in the patient and control individuals. A 50% decrease in the level of arylsulfatase‐A confirmed a small deletion in 22q(22q13.2 → qter), and additional studies localized more precisely the loci for α‐mannosidase (cytoplasmic) and β‐galactosidase.