bluuebunny/crossref_metadata_2025 huggingface dataset:
Borderline normal intelligence in the Smith‐Lemli‐Opitz (RSH) syndrome
Authors: Lowry R. Brian , Yong Siu‐Li , Opitz John M.
Published: June 2005

We report two sibs with the Smith‐Lemli‐Optiz (RSH) syndrome and intelligence in the borderline normal range. The proposita has all the features of the syndrome; however, her brother shows fewer signs, indicating that considerable variability of expression may exist for this autosomal recessive trait. Nearly all previous cases had severe to profound mental retardation. The incidence of the syndrome in British Columbia is approximately 1/40,000 live births, giving a heterozygote frequency of about 1/100.
Genetic counseling dilemmas: Down syndrome, paternal age, and recurrence risk after remarriage
Authors: Hook Ernest B. , Karp Laurence E.
Published: June 2005

The recent demonstration that about 20–30% of cases of Down syndrome are of paternal origin has again raised interest in the question of the possible contribution of paternal age independent of maternal age to a couple's risk of a Down syndrome live birth. In this paper the nature of the available evidence is critically reviewed, interpretations reconciling differences between studies that reached opposite conclusions are presented, and an approach to genetic counseling in the face of such apparent differences in the literature is discussed. It is not likely that data from ad hoc studies of parental origin of the extra chromosome will be sufficient to judge the existence or magnitude of paternal age‐specific risk, and reliance must be made on statistical studies that searched for paternal age effects while controlling for maternal age. The literature is consistent with an apparent doubling of risk for paternal age 55 and over, but no effect at younger paternal ages. With regard to remarriage, it is suggested that if members of a couple with a 47, +21 child remarry it be assumed that the excess risk “travels” to that new couple which includes the parent in whom non‐disjunction occurred in the previous marriage. If parental origin is not known, it is suggested that the risk be calculated on the assumption of a 20–30% likelihood that it was of paternal origin and a 70–80% likelihood that it was of maternal origin, and that the excess empiric risks be apportioned accordingly in the new marriages.
Trisomy 6q25→6qter in two sisters resulting from maternal 6;11 translocation
Authors: Clark Constance E. , Cowell Henry R. , Telfer Mary A. , Casey Pamela A.
Published: June 2005

Chromosome banding was used to define a partial duplication of the long arm of chromosome 6 (6q25→6qter) in two profoundly affected sisters and to identify their phenotypically normal mother and sister as balanced translocation carriers whose karyotypes were interpreted as 46,XX,t(6;11) (q25;q25). Prominent clinical features included profound mental retardation, hypertelorism, micrognathia, down‐turned mouth, dental anomalies, clubfeet, webbed neck, late progressive scoliosis, flexion contractures, and low total finger ridge count. By comparison with published reports, it has been possible to establish a trisomy 6q25→6qter syndrome.
Endocardial fibroelastosis, neurologic dysfunction and unusual facial appearance in two brothers, coincidentally associated with dominantly inherited macrocephaly
Authors: Jennings Mark T. , Hall Judith G. , Kukolich Mary
Published: June 2005

We describe two brothers with endocardial fibroelastosis, unusual facial appearance, and cryptorchidism. The surviving brother has mental retardation, seizures and possible hypothalamic dysfunction. Both brothers have a head size greater than two standard deviations above normal; this appears to be related to superimposed presence of coincidental autosomal dominant macrocephaly in this family.
Chromosome findings in 2,500 second trimester amniocenteses
Authors: Crandall Barbara F. , Lebherz Thomas B. , Rubinstein Lidia , Robertson Robert D. , Sample William F. , Sarti Dennis , Howard Judy , Opitz John M.
Published: June 2005

We have analyzed the chromosome abnormalities found in 2,500 amniocenteses for prenatal diagnosis; 1,887 (75%) were performed because the maternal age was 34 years or more. Chromosome abnormalities were detected in 1.80% of those referred for advanced maternal age, 1.2% between ages 34 and 39 years and 4.6% 40 years and over. Of these, four occurred in women who would have been 34 years at delivery (2.9%). Trisomy 21 accounted for 50% of the chromosome abnormalities; sex chromosome abnormalities, for 25%; the remaining 25% was divided equally between trisomy 18 and partial trisomies and mosaics. Unexpected translocations were found in 0.4%, of which two‐thirds were balanced and identified in one parent. The accuracy was 99.6%.
Syndactyly: Frequency of specific types
Authors: Castilla Eduardo E. , Paz Joaquin E. , Orioli‐Parreiras Iêda M. , Opitz John M. , Hermann Jürgen
Published: June 2005

Syndactyly without other combined limb anomalies, Poland complex, or amniotic bands, was diagnosed in 174 of 599, 109 consecutive newborn infants (3/10,000). Syndactyly was the only diagnosed anomaly in 133 cases, and it was associated with other anomalies in 41. The most common type of syndactyly was isolated syndactyly of the second and third toes (70 cases), which affected more males than females, and had a higher than expected frequency of white non‐Latin‐European ancestry. The second most frequent type was isolated syndactyly of the middle and ring fingers (18 cases), and the third was isolated syndactyly of the fourth and fifth toes (13 cases). Considering both isolated and syndromal cases, 66% (114/172) could be assigned to one or another of the fourth genetic categories of syndactyly described by Temtamy and McKusick [1978]. This, plus the high frequency of affected first degree relatives observed (25/434:6%), suggests that the genetic forms of syndactyly may be more common than might be suspected from the small number of pedigrees in the literature.
Hallux varus and preaxial polysyndactyly in brothers
Authors: Kleiner Beth C. , Holmes Lewis B.
Published: June 2005

Two brothers with hallux varus of both feet are reported. One brother also had duplication/triplication of the great toes. The parents had no skeletal abnormalities or abnormalities of dermatoglyphics.
The birth prevalence of malformation syndromes in Tokyo infants: A survey of 14,430 newborn infants
Authors: Higurashi Makoto , Iijima Kumiko , Sugimoto Yôko , Ishikawa Norihiko , Hoshina Hiroki , Watanabe Nobuo , Yoneyama Kuniyoshi , Miller James R. , Opitz John M.
Published: June 2005

A survey of the birth prevalence of congenital anomalies among newborn infants in Japan is under way at a large maternity hospital in Tokyo. Of 14,430 consecutive newborn babies (7,455 M; 6,975 F), 33 had a multiple congenital anomalies (MCA) syndrome. These included 2 with trisomy 13 (including a mosaic), 3 with trisomy 18 (including 1 mosaic), 16 with trisomy 21 (including 1 mosaic), 1 with cri‐du‐chat syndrome, 1 with 5p partial trisomy, 1 with Hallermann‐Streiff syndrome, 1 with Treacher‐Collins syndrome, 1 with achondroplasia, 2 with arthrogryposis multiplex congenita, 1 with hemihypertrophy, 1 with Wiedemann‐Beckwith syndrome, 1 with asplenia syndrome, 1 with Klippel‐Trenaunay‐Weber syndrome, and 1 with probable Marfan's syndrome. Except for one infant with Ullrich‐Turner syndrome, cases with sex‐chromosome aberrations could not be diagnosed neonatally on a clinical basis.
Familial joint instability syndrome
Authors: Horton William A. , Collins Debra L. , DeSmet Arthur A. , Kennedy James A. , Schimke R. Neil , Opitz John M.
Published: June 2005

We describe a family in which many persons have generalized joint laxity frequently complicated by dislocation of major joints. The condition is an autosomal dominant trait, with high penetrance. The disorder observed in this family and in others from the literature appears to be a specific syndrome that can be distinguished from other familial forms of joint laxity such as simple familial joint laxity and the Ehlers‐Danlos syndromes. It has been designated the familial joint instability syndrome.
Hallux duplication, postaxial polydactyly, absence of the corpus callosum, severe mental retardation, and additional anomalies in two unrelated patients: A new syndrome
Authors: Schinzel A. , Schmid W.
Published: June 2005

Two unrelated patients, a 4‐year‐old boy and a 2 1/2‐year‐old girl, presented with a similar pattern of abnormalities. Both had severe mental retardation, macrocephaly, absence of the corpus callosum, unusual facial appearance, duplication of hallucal phalanges, postaxial hexadactyly of finger phalanges, and 2/3‐syndactyly of toes. The boy also had postaxial hexadactyly of toe phalanges, inguinal hernias and umbilical hernia, and growth retardation. We suspect a common cause of this apparently “new” syndrome, most likely a gene mutation.
A 48,XXXX female with absence of ovaries
Authors: Collen Roberta J. , Falk Rena E. , Lippe Barbara M. , Kaplan Solomon A.
Published: June 2005

A 16 1/2‐year‐old phenotypic female had primary amenorrhea, mild mental retardation, radiounar synostosis, and other minor anomalies. Chromosome constitution of leukocytes and skin fibroblasts was 48,XXXX. Plasma levels of gonadotropins were increased, and those of estrogens, decreased consistent with ovarian failure. Laparoscopy showed a small midline uterus, and 2 fallopian tubes, and fimbriae. Neither ovaries nor gonadal streaks were seen on either side. This patient appears to represent the first instance of 48,XXXX aneuploidy with documented absence of ovaries.
Achalasia and microcephaly
Authors: Dumars Kenneth W. , Williams James J. , Steele‐Sandlin Constance , Holmes Lewis B.
Published: June 2005

The authors report the combination of achalasia, microcephaly, and mental retardation in three surviving sisters and similar manifestations in a brother who died after recurrent vomiting and respiratory infections. The achalasia in the females was relieved with an operation. There was no demonstrable chromosomal abnormality. In this family achalasia, microcephaly, and mental retardation occurred together as an apparent autosomal recessive syndrome.
Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly—a new syndrome? Part I: Clinical, causal, and pathogenetic considerations
Authors: Hall J. G. , Pallister P. D. , Clarren S. K. , Beckwith J. B. , Wiglesworth F. W. , Fraser F. C. , Cho S. , Benke P. J. , Reed S. D. , Optiz John M.
Published: June 2005

We report on six infants with a neonatally lethal malformation syndrome of hypothalamic hamartoblastoma, postaxial polydactyly, and imperforate anus. Some, but not all, patients had laryngeal cleft, abnormal lung lobulation, renal agenesis and/or renal dysplasia, short 4th metacarpals, nail dysplasia, multiple buccal frenula, hypoadrenalism, microphallus, congential heart defect, and intrauterine growth retardation. The infants also had hypopituitarism and hypoadrenalism.

All were sporadic cases, parents were not consanguineous, chromosomes were apparently normal. Family histories were unremarkable. There was insecticide and/or herbicide exposure in several of the cases, but no exposures were common to all 6 mothers. Five of the patients were born within an 8‐month period, but all in different geographic locations. It is postulated that this is a previously apparently unreported syndrome of presently unknown cause.
Multiple pterygium syndrome
Authors: Chen Harold , Chang Chung‐Ho , Misra Raghunath P. , Peters Henry A. , Grijalva Noel Sandino , Opitz John M. , Lowry R. Brian
Published: June 2005

We describe a sporadic case and four sibs from a consanguineous Nicaraguan family affected with the multiple pterygium syndrome. Clinical manifestations included normal intelligence; short stature; pterygia of neck, axillary, antecubital, popliteal, digital, and intercrural areas; multiple joint contractures with a crouched stance; a flat, sad, motionless facial appearance; and cleft palate. Males had small penis and scrotum and cryptorchidism; females had apparent aplasia of labia majora and small clitoris. Skeletal anomalies included fusion of cervical vertebrae, scoliosis, flexion contractures of fingers and “rocker‐bottom” feet with vertical talus. This review documents genetic heterogeneity: Autosomal recessive inheritance in many cases, autosomal dominant determination in others, and sporadic occurrence.
Dicentric Y chromosome arising via tandem translocation
Authors: Herva Riitta , Saarinen Irja , Savikurki Helka , de la Chapelle Albert , Optiz John M.
Published: June 2005

We describe a 22‐year‐old woman with primary amenorrhea, bilateral gonadoblastomas, and short stature (148.0 cm), but no other signs of the Ullrich‐Turner syndrome. There were three cell lines identified in peripheral blood lymphocytes – 45,X (30%), 46,XY (60%), and 46,X,tan dic(Y) (10%). Cells cultured from gonadal biopsies showed only the 45,X karyotype. However, frozen sections of the biopsies showed frequent single and rare double‐Y‐chromatin bodies. Lymphocytes were H‐Y antigen‐negative.

This previously undescribed structurally abnormal chromosome probably consists of two Y chromosomes attached end‐to‐end in a tandem translocation. One of the centromeres forms the primary (functional) constriction, the other being detectable only as C‐positive material on each chromatid, so presumably inactive. The discrepancy between the presence of Y‐chromatin in frozen sections of the gonads and its absence from karyotype in gonadal cultures is indicative of cell selection in tissue culture. Finally, the case confirms the high risk of gonadoblastoma in women with a Y chromosome, even in the absence of H‐Y antigen.
Duplication 12q mosaicism in two unrelated patients with a similar syndrome
Authors: Harrod M. J. E. , Byrne J. B. , Dev V. G. , Francke Uta , Optiz John M.
Published: June 2005

Two unrelated children with a similar syndrome were found to have mosaicism for a cell line containing one chromosome 12 with an additional faintly G‐banding staining region that apparently represents a duplication of the distal portion of the long arm. The homolog and the other chromosomes are normal, as are the parental chromosomes. The remarkable phenotypic similarity of the 2 patients and their resemblance to 2 previously reported patients with duplication of the same chromosome region suggests that duplication 12q24 results in a clinically identifiable malformation syndrome.
Effects of chromosome constitution on growth and longevity of human skin fibroblast cultures
Authors: Hoehn H. , Simpson M. , Bryant E. M. , Rabinovitch P. S. , Salk D. , Martin G. M. , Optiz John M.
Published: June 2005

Employing standardized cell‐culture methods, 10 euploid and 22 constitutionally aneuploid human skin fibroblast strains were assessed in triplicate for total growth potential, growth rates, population‐doubling times, and cloning. In addition, longitudinal growth rate studies were carried out with otherwise isogenic 45,X and 47,XXX clonal cultures derived from a mosaic parental strain. Growth rates and longevities were cell‐strain specific and highly reproducible among sister cultures of a given strain. There was no systematic correlation between chromosome constitution and any of the measured growth parameters. Trisomic as well as monosomic strains showed the same degree ofvariability with respect to these parameters as did euploid cultures. In particular, 4 trisomy 21 strains were not unusually short‐lived, nor were clones with the 47,XXX constitution compared to those with 45,X karyotypes.

We therefore conclude that the cumulative number of in vitro doublings preceding senescence of fibroblast‐like cells cultured from skin does not differ significantly among cultures derived from humans who have a normal karyotype, trisomy 13, 18, or 21, the 45,X constitution, or various combinations of extra X and Y chromosomes.
Plasma exchange removes glycosphingolipid in Fabry disease
Authors: Pyeritz Reed E. , Ullman M. David , Moser Ann B. , Braine Hayden G. , Moser Hugo W. , Optiz John M.
Published: June 2005

In a man with Fabry disease, basal plasma glycosphingolipid (GSL) levels were determined by high‐performance liquid chromatography (HPLC). A series of three alternate‐day plasma exchanges transiently lowered plasma ceramide trihexoside (CTH) to normal. A total of 70 μmoles of CTH were removed by eight plasma exchanges. If future studies show that pathologic tissue accumulations of CTH are reduced by plasma exchange, then long‐term repetitive plasma exchange could be used as treatment until enzyme replacement is practical.
Familial occurrence of bifid femur and monodactylous ectrodactyly
Authors: Gollop T. R. , Lucchesi E. , Martins R. M. M. , Nione A. S. , Optiz John M.
Published: June 2005

Two brothers each hada one normal upper limb; one had tridactylous ectrodactyly of one hand with normal forearm bones; the other had monodactyly of one hand with absent ipsilateral ulna. Both had monodactyly of the feet, absence of the tibiae, and unilateral bifurcation of the femur. A sister of the paternal grandfather was purportedly similarly affected. Since her parents and the father and paternal grandfather of the affected boys were normal, the pattern of inheritance of the trait in this family is presently unclear.
Genetic associates/counselors in genetic services
Authors: Kessler Seymour , Optiz John M.
Published: June 2005

A survey of US directors of genetic services showed that about 38% of the non‐physician professionals providing such services are genetic associates/counselors (GAs). Over 90% of GAs appear to be involved in direct human services, rather than in the performance of laboratory procedures or research.

Although they wanted GAs to be competent in communication and inter‐personal skills, counseling, and community education, employers and potential employers tended to rank a background preparation in and knowledge of psychosocial principles relatively less important than a knowledge of biological principles. The possible consequences of these attitudes are discussed in light of the fact that GAs represent a new profession which is still evolving and struggling to define its professional role in genetic services. Despite some role ambiguities, employers familial with their work expressed a strong vote of confidence in these professionals.
Frequency of the branchio‐oto‐renal (BOR) syndrome in children with profound hearing loss
Authors: Fraser F. C. , Sproule J. R. , Halal F. , Optiz John M.
Published: June 2005

Nineteen of 421 white children in Montreal schools for the deaf had preauricular pits. The branchio‐oto‐renal (BOR syndrome was identified in four of the nine families who agreed to family investigation, including audiograms and intra‐venous pyelograms (IVPs), and may have been present in several others. The penetrance of this autosomal dominant syndrome appears to be high. It is estimated that severe renal dysplasia occurs in about 6% of heterozygotes. The presence of a preauricular pit at birth suggests that the child has at least one chance in 200 of severe hearing loss, and this warrants a careful family history, as well as alertness for any signs of hearing impairment. Offspring of affected individuals are eligible for prenatal diagnosis of renal dysplasia.
Limitations of amniography in the prenatal diagnosis of spina bifida
Authors: Fernhoff Paul M. , Marion Janet P. , Priest Jean H. , Optiz John M.
Published: June 2005

A fetus with an open, noncystic myelomeningocele was detected at the 22nd week of gestation in a woman monitored for advanced maternal age. The lesion could not be demonstrated on amniography. In 13% of published reports amniography failed to detect significant spina bifida lesions. This false‐negative rate seems related to the noncystic nature of some neural tube defects at midgestation.
The syndrome of multisynostotic osteodysgenesis with long‐bone fractures
Authors: DeLozier C. Dawn , Antley Ray M. , Williams Rick , Green Neil , Heller Richard M. , Bixler David , Engel Eric , Optiz John M.
Published: June 2005

Described here are two patients with a newly recognized syndrome of bone and cartilage maldevelopment which, we believe, results from a single embryonic defect, probably of genetic origin. The cardinal manifestations of this association are craniosynostosis, radiohumeral synostosis (RHS), and femoral bowing. Specific secondary defects include midface hypoplasia with characteristic facial appearance and ears, neonatal femoral fractures, and multiple minor anomalies of the limbs. Though the differential diagnosis includes such disorders as the campomelic syndrome, osteogenesis imperfecta (OI) and certain of acrocephalosyndactyly syndromes, the unique combination of clinical and radiographic abnormalities allows ready differentiation. The cause cannot be determined from these two cases.
Nonspecific X‐linked mental retardation II: The frequency in British Columbia
Authors: Herbst Diana S. , Miller James R.
Published: June 2005

Data on nonspecific mental retardation in two or more sibs ascertained from the British Columbia Health Surveillance Registry are utilized to calculate the frequency of X‐linked mental retardation in the population of British Columbia (B.C.). In the 1950–1969 birth cohort there are 107 sibships with only males affected and 35 sibships with only females affected giving an excess of 72 male‐affected sibships. Family histories of the sibships with two or more mentally retarded males provide evidence that the mothers of the excess of male‐affected sibships are carriers of X‐linked mental retardation. Thus, a frequency of 1.83 per 1,000 males for X‐linked mental retardation and a carrier frequency of 2.44 per 1,000 females are calculated. This frequency can account for all of the excess of males in the population who are affected with nonspecific mental retardation. We estimate that seven to 19 X‐linked genes exist to cause nonspecific mental retardation, and that the frequency of the marker‐X chromosome, associated with X‐linked mental retardation in some families, may be 0.92 per 1,000 male births.
Confidence bands for the growth of head circumference in achondroplastic children during the first year of life
Authors: Dawson Deborah V. , Todorov Alexandre B. , Elston Robert C.
Published: June 2005

Confidence bands are established for the growth of head circumference in achondroplastic children during their first year of life. The model
equation image
where a = (1, t,t2) and t is age expressed in months provides the best estimated propulation mean curve with 95% confidence limits.
The “long‐thumb” brachydactyly syndrome
Authors: Hollister David W. , Hollister William G.
Published: June 2005

A unique variety of brachydactyly associated with skeletal and joint anomalies and possible cardiac conduction defects has been observed in three generations of one family in a pattern consistent with autosomal‐dominant transmission. This combination of anomalies has not previously been seen together as a single syndrome. We report clinical and radiographic studies in three of the four affected family members.
An infant with duplication of 17q21→17qter
Authors: Gallien J. U. , Neu R. L. , Wynn R. J. , Steinberg‐Warren N. , Bannerman R. M. , Opitz John M.
Published: June 2005

Duplication of the distal part of 17q has been reported in 4 patients [1, 2]. We are reporting clinical, autopsy, and cytogenetic data on an additional patient whose condition was due to a familial translocation in which the patient's chromosome constitution is 46,XX,der(4),t(4;17)(p16;q21) pat. The phenotype of the five known patients with this duplication is very similar, and their manifestations are distinct enough to be clinically recognizable. Abnormalities common to all five patients are severe growth impairment, craniofacial anomalies with severe hypertelorism, frontal bossing and temporal narrowness, a widow's peak, narrow palpebral fissures, a thin upper lip overlapping a thin lower lip with down‐turned corners of the mouth, micrognathia, apparently low‐set and deformed ears, short webbed neck, and hyperlaxity of the limbs.
Spondylocostal dysostosis associated with anal and urogenital anomalies in a Mennonite sibship
Authors: Casamassima Anthony C. , Morton Cynthia Casson , Nance Walter E. , Kodroff Michael , Caldwell Robin , Kelly Thaddeus , Wolf Barry
Published: June 2005

Spondylocostal dysostosis, anal atresia, and urogenital anomalies were observed in two male infants of a consanguineous Mennonite couple. A careful review of previously reported syndromes of severe vertebral abnormalities and/or imperforate anus suggests that our patients have a previously undescribed recessive disorder that should be included in the differential diagnosis of rib and vertebral anomaly syndromes.
Long survival in Trisomy‐13‐syndrome: 21 cases including prolonged survival in two patients 11 and 19 years old
Authors: Redheendran R. , Neu R. L. , Bannerman R. M. , Opitz John M.
Published: June 2005

The mean survival in Trisomy‐13‐syndrome patients is reported to be 130 days. We have diagnosed 21 cases of this syndrome in this institution (11 females and 10 males); 15 patients had regular trisomy 13 and 6 had translocation‐trisomy 13 karyotypes. The mean survival of the 19 patients who died was 97.05 days; translocation patients survived longer than regular trisomy patients. The oldest living patients with trisomy 13 are a girl 19 and a boy 11 years old. Both are black, have regular trisomy 13 karyotypes and have had most of the manifestations of the syndome. No mosaicism was detected in repeated cytogenetic studies. The 19‐year‐old patient is the oldest known living person with regular trisomy 13.
Two locus models for gluten sensitive enteropathy: Population genetic considerations
Authors: Greenberg David A. , Rotter Jerome I. , Opitz John M.
Published: June 2005

Familial occurrence of coeliac disease (gluten‐sensitive enteropathy, GSE) is well known, but the mode of inheritance remains unclear. Peña et al proposed that the genetic basis for GSE was due to disease‐predisposing alleles at two loci: DRw3 at the HLA‐D locus and a GSE‐associated B‐cell alloantigen at another, unlinked locus. They concluded that clinical disease required one DRw3 (dominant inheritance) and two B‐cell alloantigen alleles (recessive inheritance), but the observed gene frequencies were not consistent with the observed disease prevalence. Here we examine the gene frequencies allowed, assuming a 2‐locus model, under the constraints of known disease prevalence limits and the segregation ratio calculated from 42 published families.

The gene frequencies found by Peña et al predict the segregation ratio observed in the published pedigrees and the best estimates of disease prevalence of GSE, provided (1) a 2‐locus model is assumed and (2) both loci exhibit recessive inheritance. The segregation ratio appears incompatible with a 2‐locus dominant‐recessive model without assuming reduced penetrance.
Cartilage‐hair hypoplasia, defective T‐cell function, and Diamond‐Blackfan anemia in an Amish child
Authors: Harris Richard E. , Baehner Robert L. , Gleiser Sonia , Weaver David D. , Hodes M. E. , Opitz John M.
Published: June 2005

An Amish boy with cartilage‐hair hypoplasia (CHH) and cell‐mediated immunodeficiency developed “congenital” hypoplastic anemia (CHA) of the Diamond‐Blackfan type by two months. Alterations of T cell function have been described separately in CHH and CHA, but this is the first known report linking the two conditions. The patient has two relatives with CHH, one with associated leukemia and one with Hodgkin disease.
Kaufman syndrome (hydrometrocolpos, polydactyly, and congenital heart disease) with pituitary dysplasia, choanal atresia, and vertebral anomalies
Authors: Knowles John C. , Brandt Ira K. , Bull Marilyn J. , Opitz John M.
Published: June 2005

An infant was found to have the previously known manifestations of the Kaufman syndrome (hydrometrocolpos, postaxial polydactyly, and congenital heart disease) but also imperforate anus, malrotation of gut, congenital hip dislocation, and urogenital sinus. All of these anomalies have been separately reported in other cases of the syndrome. Three previously unreported problems present in this case were choanal atresia, pituitary dysplasia, and vertebral anomalies; these may well be component manifestations of the syndrome and not sporadic occurrences in our patient. Of particular clinical importance were the hypoglycemia and the hypoglucocorticism secondary to the pituitary dysplasia.
Dermatoglyphics in medicine—problems and use in suspected chromosome abnormalities
Authors: Reed Terry , Opitz John M.
Published: June 2005

Dermatoglyphic findings in patients with chromosome abnormalities are reviewed including the more common aneuploidies and recently recognized deficiency and duplication syndromes. Tables of dermatoglyphic changes are provided to help in the diagnosis of patients with suspected chromosome abnormalities. Finally, problems of dermatoglyphic nomenclature and statistics are considered. It is emphasized that dermatoglyphics should be used in conjunction with the physical examination rather than as an independent diagnostic test.
Holoprosencephaly in monozygotic twins – clinical and computer tomographic findings
Authors: Burck Uta , Hayek Hubert W. , Zeidler Udo , Opitz John M.
Published: June 2005

Of monozygotic male twins with holoprosencephaly, one showed by computer tomographic (CAT) scan a mild type with orbital hypotelorism, flat nose, bilateral cleft lip, and cleft palate associated with an intermaxillary rubital hypotelorism, flat nose, absent nasal bridge, and median cleft lip.

Lymphocyte chromosomes were apparently normal.

A review of the literature shows a heterogenous patient material in that most pertinent cases involved dizygotic twins, and some of these presumably had chromosome abnormalties.
Developmental screening tests in achondroplastic children
Authors: Todorov A. B. , Scott C. I. , Warren A. E. , Leeper J. D. , Opitz John M.
Published: June 2005

Data on psychomotor de development are compiled on 197 achondroplastic children. The data are plotted in a manner similar to that used in the Denver Developmental Screening Test. Gross motor development is delayed in achondroplastic children as compared to children of approriate age. There is no difference in language development.
Polymorphic variants in human chromosome 15
Authors: Chen T. R. , Kao M. L. , Marks J. , Chen Y. Y. , Opitz John M.
Published: June 2005

We found eight polymorphic variants in human chromosome 15 using Q, C, Q‐C and Ag‐NOR staining methods. These variants included brightly or dully fluorescent pericentric segments and satellites, giant satellites, increased amounts of short arm heterochromatin (ph+) and darkly (C band‐positive) or lightly (C band‐negative) Giemsa‐stained pericentric Q‐negative segments. These staining properties indicated that the entire short arm of 15 contained at least four distinct chromatin segments: Q‐negative centrometric heterochromatin, a Q‐vriable distal segment, a Q‐negative satellite stalk, and Q‐variable satellites, in that order, from proximal to distal ends. The Brd U‐Hoechst 33258‐stained R bands (RBH) and high resolution G subbands were also studied for karyologic characterization of chromosome 15. Most of these variants were reported also in 13, but insufficiently documented in other D and G chromosomes. Together with polymorphic pericentric fluorochromes seen in 3 and 4, Yq, and nonpathogenic t(D;Yq), the pattern of these variants can be used as karyologic fingerprints for identification of each individual and his or her cell explants both in vivo and in vitro.
Spectrum of anomalies in the Meckel syndrome, or: “Maybe there is a malformation syndrome with at least one constant anomaly”
Authors: Fraser F. Clarke , Lytwyn Alice , Opitz John M.
Published: June 2005

The Meckel syndrome coimparises a variety of defects including the classical triad of occipital encephalocele, cystic kidneys, and poly dactyly. The frequencies of the various defects are more accurately represented in the affected sibs of probands than in the probands themselves, since the latter are selected according to severity and preconceived notions of what constitutes the syndrome. In a series of 38 such sibs, all had cystic dysplasia of the kindney, 63% had an occipital meningocele, 55% had polydactyly, and 18% had no reported brain malformation. In families in which the proband had the classical triad, only 68% of the affected sibs had it. It is concluded that the diagnosis of Meckel syndrome may not be valid in the absence of cystic kidney dysplasia. In babies with encephalocele or anencephaly, pathologic examination, particularly of the kidneys, is important in determining risk of recurrence. This approach to estimating the variability of a syndrome might profitably be extended to other genetically determined pleiotropic conditions.
Some considerations bearing on the doctrine of self‐fulfilling prophecy in sex chromosome aneuploidy
Authors: Puck Mary H. , Herrmann Jürgen
Published: June 2005

The doctrine of self‐fulfilling prophecy has been invoked in studies of the effects of sex chromosome aneuploidy on human development as a reason for routine concealment of the diagnosis from affected children and their families. It has been assumed that knowledge of the existence of risk for deviance from normal development automatically creates a self‐defeating emotional climate. This communication attempts to delineate both advantageous and deleterious aspects of self‐fulfilling prophecy in the medical management of sex chromosome aneuploidy, presents an alternative approach, and reviews the experience in a prospective study of 52 families where a policy of disclosure was followed.
The Gordon syndrome: Autosomal dominant cleft palate, camptodactyly, and club feet
Authors: Robinow Meinhard , Johnson G. Frank , Opitz John M.
Published: June 2005

The triad of camptodactyly, club feet, and cleft palate, called the Gordon syndrome, is a rare autosomal dominant trait with variable expressivity, known from only three previously described families. Here we report the condition in a mother and her daughter. They also had several previously undescribed anomalies, which suggests that the Gordon syndrome is a more complex malformation syndrome than previously suspected.
Hypospadias: An epidemiological study in Latin America
Authors: Neto Roque Monteleone , Castilla Eduardo E. , Paz Joaquin E. , Opitz John M.
Published: June 2005

Epidemiological variables in relation to hypospadias were analyzed in a case‐control study of a liveborn population from six Latin American countries. The frequency of hypospadias was 7.6 per 10,000 livebirths (324/423,839). The cases were divided into three types: distal (72%), proximal (18.5%) and non‐specified cases (9.5%). The control group consisted of the first nonmalformed child born after each of the patients and was matched by sex, place, and time of birth. Other coexisting malformations were found in 13.6% of cases. The Brazilian sample showed the highest incidence rate (17.7/10,000) and also the highest incidence of severe forms (5.0/10,000) as compared with the other countries.

A circannual rhythm was detected using several different statistical procedures. Low mean birth weight, twinning, vaginal bleeding, and drug exposure during the 1st trimester (particularly sex hormones) were found to be risk factors. The more severe forms had a higher neonatal mortality rate and higher inbreeding when compared with the controls or milder forms. The heritability coefficient was 0.6772 ± 0.0675. The possible role of maternal sex hormone intake and disturbances of human chorionic gonadotropin during the first trimester are discussed.
A comprehensive scoring system for evaluating noonan syndrome
Authors: Duncan W. J. , Fowler R. S. , Farkas L. G. , Ross R. B. , Wright A. W. , Bloom K. R. , Huot D. J. , Sondheimer H. M. , Rowe R. D. , Opitz John M.
Published: June 2005

A multidisciplinary team assessed 23 patients with various manifestations of the Noonan syndrome, including pulmonary valve stenosis (with leaflet dysplasia), “typical” facial appearance (including hypertelorism, epicanthic folds, flat nasal bridge, and apparently low‐set ears), short stature, and mental retardation. Seven patients had a family history of the syndrome. A comprehensive scoring system was devised on the basis of frequency and severity of manifestations and results of invasive and noninvasive tests in these patients and those reported in the literature. The scoring system was condensed into a score card for clinical use and validated by “blind” application to patients with isolated pulmonary valve stenosis or suspected Noonan syndrome. Use of a scoring system to diagnose a syndrome for which there is no specific diagnostic test facilitates accuracy and decreases observer bias. In the case of unusual congenital disorders it is particularly valuable for a pediatrician in general practice.
Amniocyte clones for prenatal cytogenetics
Authors: Hecht F. , Peakman D. C. , Kaiser‐McCaw B. , Robinson A.
Published: June 2005

Amniotic fluid cells were processed in situ on coverslips in 1,429 consecutive cases from Colorado and Arizona. Two true chromosome mosaics were differentiated from 39 pseudomosaics with clarity by the method described here in detail. The culture failure rate was 1–2% and the error rate was 0% in both laboratories. The time in culture prior to the initial harvest for the last 329 cases was 8.7 days.
Genetic counseling: A comparison of counselee's genetic knowledge before and after (part III)
Authors: Seidenfeld M. J. , Antley R. M. , Opitz John M.
Published: June 2005

Forty‐seven mothers of children with Down syndrome were evaluated on their knowledge of genetic facts pertaining to Down syndrome. We found that more knowledge of this disorder was acquired by counselees before counseling than from the counseling. The data show that counseling is most effective in enhancing counselees' knowledge of general genetics, ie, the origin of the extra chromosome in a child with Down syndrome. In contrast, counselees had the most difficulty in learning the recurrence risks for others, including the risks for relatives, siblings, and the population in general.

A finding of practical importance is that formal education is inversely related to the amount of information counselees learned from counseling. Mothers with less than a high school education acquired most of their genetic knowledge from counseling, while those with more than a high school education acquired most of this information before counseling.
The dup(3q) syndrome: Report of eight cases and review of the literature
Authors: Steinbach P. , Adkins W. N. , Caspar H. , Dumars K. W. , Gebauer J. , Gilbert E. F. , Grimm T. , Habedank M. , Hansmann I. , Herrmann J. , Kaveggia E. G. , Langenbeck U. , Meisner L. F. , Najafzadeh T. M. , Opitz J. M. , Palmer C. G. , Peters H. H. , Scholz W. , Tavares A. S. , Wiedeking C. , Opitz John M.
Published: June 2005

Clinical and cytogenetic examinations were performed on eight unrelated infants with duplication of part of the long arm of chromosome 3. A review of published cases shows a clinical syndrome characterized by statomotoric retardation, shortened life span, and a multiple congenital anomalies (MCA) syndrome of abnormal head configuration, hypertrichosis, hypertelorism, ocular anomalies, anteverted nostrils, long philtrum, maxillary prognathia, down turned corners of the mouth, highly arched or cleft palate, micrognathia, malformed auricles, short, webbed neck, clinodactly, simian crease, talipes, and congenital heart disease. The dup(3q) syndrome is a clinically easily recognizably entity.
Corticosteroid‐induced cleft lip in mice: A teratologic, topographic, and histologic investigation
Authors: Melnick Michael , Jaskoll Tina , Slavkin Harold C. , Opitz John M.
Published: June 2005

Unlike cleft palate, relatively few teratogens have been found to induce cleft lip in mice. The present study was designed to assess the teratologic, topographic (SEM), and histologic effects on lip morphogenesis following the administration of triamcinolone hexacetonide on the eighth day of gestation. The frequency of cleft lip in treated A/J mice was found to be more than three times greater than the spontaneous frequency in untreated controls. Comparable studies with other murine strains suggest no association between the cleft lip response and either a maternal effect or the H‐2 complex. Affected A/J embryos showed a severe reduction in the size of the lateral nasal processes; affected embryos also demonstrated localized cell type‐specific alterations, particularly in the epithelia and at the interface between epithelium and mesenchyme.
A 49,XXXYY male
Authors: Salamanca‐Gòmez Fabio , Cortès Richardo , Sànchez Josefina , Armendares Salvador , Opitz John M.
Published: June 2005

In a 29‐year‐old male with severe mental retardation, hypogenitalism, and congenital malformations we identified a 49,XXXYY chromosome constitution by Q, G, and C banding techniques. The clinical, cytogenetic, and endocrine findings are discussed and compared with those of the two previously described cases with this sex chromosome anomaly in an attempt to begin delineation of the condition.
Failure to demonstrate an effect of in vivo diagnostic ultrasound on sister chromatid exchange frequency in amniotic fluid cells
Authors: Lundberg Max , Jerominski Leslie , Livingston Gordon , Kochenour Neil , Lee Timothy , Fineman Robert , Opitz John M.
Published: June 2005

Antepartum use of diagnostic ultrasound has markedly reduced radiation exposure of the fetus. Previous investigations have documented the safety of ultrasound, but concern persists regarding its long‐term effects. As new methods become available to study possible subtle effects of ultrasound, it is important to reevaluate this technique continually because of its universal use in obstetrics and elsewhere. We report results of in vivo studies of effect of diagnostic ultrasound on the sister chromatid exchange (SCE) frequency in amniotic fluid cells. SCE is a cytogenetic phenomenon believed to be a sensitive indicator of environmental perturbations and chromosome stability. In amniotic fluid cells from six pregnancies without ultrasound exposure and in 34 pregnancies that received varying amount of ultrasound immediately before amniocentesis, there was no difference in SCE frequency in exposed versus nonexposed cells. These data, which appear to confirm again the safety of ultrasound, are reassuring to both patients and clinicians.
Prenatal diagnosis in 3,000 women for chromosome, X‐linked, and metabolic disorders
Authors: Daniel Art , Stewart Lesley , Saville Toni , Brookwell Ross , Paull Helen , Purvis‐Smith Stuart , Lam‐Po‐Tang P. R. L. C. , Jacobs Patricia , Hsu Lillian
Published: June 2005

In 3,000 women referred for prenatal diagnosis, 110 (3.7%) abnormal fetuses were detected and 85 therapeutic terminations were performed. There were five main reasons for referral. Among the 2,227 women referred because of maternal age 35 years and older, there were 51 (2.3%) who had aneuploid fetuses. In the 297 women referred because of a previous child with Down syndrome, 3 aneuploid fetuses (1.0%) were detected. Of the 55 couples where one spouse was a carrier of a balanced chromosome rearrangement, 6 chromosomally abnormal fetuses were found (10.9%) (all the offspring of maternal carriers). In the latter group, five of the six heterozygotes with abnormal findings were carriers of tdic (13;21) translocations. In the 82 cases with a history of X‐linked disorders, there were 40 males (49%). Thirty‐five women were referred because of inborn errors of metabolism: 10 affected fetuses were found (28%). There was a greater proportion of sexchromosome aneuploids as compared to trisomy 21 fetuses in the 35 to 39 year maternal age group. This was reversed in the group of women 40 years old and older. Of the 25 abnormal fetuses not terminated, 6 were sex chromosome aneuploids and 10 involved X‐linked conditions where the progeny could be further prenatally monitored (eg, X‐linked hydrocephalus) or treated (eg, hemophilia). In the remaining 9 the parents expressed diverse reasons for their choice. Repeat amniocentesis was required in 2.9% of cases. One case of maternal cell contamination and one case of unconfirmed mosaicism were the only diagnostic errors found in the study. In the last 1,000 specimens referred, the average time necessary for a karyotypic result was 15.6 ± 5.6 days after amniocentesis.
Presence of H‐Y antigen in patients with ullrich‐Turner syndrome and X‐chromosome rearrangements
Authors: Haseltine Florence P. , Deponte Kathleen K. , Breg W. Roy , Genel Myron , Opitz John M.
Published: June 2005

Cells from eight of ten patients with gonadal dysgenesis and an isochromosome for the long arm of X, (i(Xq)), have been found to be H‐Y antigen‐positive, using an assay that employs rat antiserum and Raji cells. In addition, two patients with del(Xq) were also found to be H‐Y antigen‐positive, whereas four patients in whom only a 45,X line was detected were H‐Y antigen‐negative. These findings suggest that the X chromosome plays a role in the expression of H‐Y antigen in the absence of a Y chromosome. Since our patients with i(Xq) show no evidence of testicular differentiation, it is clear that there is not enough H‐Y antigen on these patients' cells to direct the development of a testis. These findings are consistent with the view that the normal functioning of genes on the X and the Y chromosomes is necessary for testicular organogenesis to occur.
Familial cavernous angiomas: Natural history and genetic study over a 5‐year period
Authors: Hayman L. Anne , Evans Robert A. , Ferrell Robert E. , Fahr Linda M. , Ostrow Peter , Riccardi Vincent M.
Published: June 2005

In a kindred of 122 individuals we found 5 individuals with cerebral vascular malformation, 3 representing typical cavernous angiomas. The condition was inherited as an autosomal dominant trait with variable expressivity. Forty‐three relatives were examined prospectively by cranial computed tomography (CCT) and lesions were found in 15; 7 were followed prospectively with CCT scans for 5 years. Angiography in 5 of these cases failed to demonstrate the lesion. In 3 patients with previously normal CCT scans a change in blood volume or membrane permeability allowed visualization of the lesion on contrast scans. In 2 individuals, both parents of affected children, a normal CCT scan was found. This emphasizes the limitations of CCT in detecting this disorder. Biochemical and red blood cell immunological genetic linkage studies were done in 36 persons. No linkage was found with any of the markers. The natural history of this disorder, characterized by marked clinical and radiographic variation in site of lesion, and the timing and severity of intracranial hemorrhage, make it a useful model for investigating contributing factors and consequences of intracranial hemorrhage in general. For atrisk and affected patients early and sequential CCTs are necessary. Familial cavernous angioma should be included in the differential diagnosis of all young persons presenting with cerebrovascular impairment, seizures, intracranial calcifications or hemorrhage.
Meiotic segregation in familial reciprocal translocation t(8q;22q)
Authors: Gödde‐Salz Elisabeth , Oesinghaus Susanne , Grote Werner , Opitz John M.
Published: June 2005

We studied the chromosomes of a mentally retarded boy with minor anomalies and of his parents using a G‐band stained high‐resolution chromosome method. This documented dup (8q24.1 → 8qter) and dup(22pter → 22q11.2) in the boy due to a maternal balanced reciprocal translocation of chromosomes 8 and 22 and 3:1 disjunction during meiosis I. The karyotype of the boy is 47, XY, + der(22) (22pter → 22q11.2::8q24.1 → 8qter). The der(22) was involved in satellite associations and stained positively with AgNO3 in mother and child. The case is compared to similar cases in the literature and the function of the small acrocentric marker chromosome during meiosis is discussed.