bluuebunny/crossref_metadata_2025 huggingface dataset:
45,X/46,XY Mosaicism. Contrast of prenatal and postnatal diagnosis
Authors: Wheeler M. , Peakman D. , Robinson A. , Henry G. , Optiz John M. , Reynolds James F.
Published: June 2005

The process of prenatal diagnosis is unique in that the diagnosis and prognosis are made without seeing the patient. 45,X/46,XY mosaicism presents a special problem in this regard. The phenotype of 45,X/46,XY postnatally diagnosed children (pediatric group) was compared to that of 6 fetuses who were diagnosed from 7,000 amniocenteses (prenatal group). These amniocenteses were performed primarily because of an increased risk of chromosome abnormality. The pediatric group (age birth—18 yr) were all phenotypically abnormal, although none were mentally retarded. Seven patients presented with ambiguous genitalia, while 2 had primary amenorrhea. Sexual assignment was changed in 2. Abnormalities included rudimentary phallus, urogenital sinus, hypospadias, undescended testes, and short stature. All 9 patients required at least one surgical procedure. In contrast, the prenatally diagnosed fetuses (ages 3 months to 31/2 yr) were all phenotypically normal males. Four were noted to have male genitalia on ultrasonography. Thus, the phenotype of 45,X/46,XY mosaicism in prenatally diagnosed fetuses can be markedly different from that of individuals diagnosed postnatally. This must be considered when counseling patients.
Callosal defect, microcephaly, severe mental retardation, and other anomalies in three sibs
Authors: Da‐Silva Elias O. , Reynolds James F.
Published: June 2005

This study concerns an apparently lethal and previously undescribed syndrome of hypoplastic corpus callosum, microcephaly, severe mental retardation, preauricular skin tag, camptodactyly, growth retardation, and recurrent bronchopneumonia. This combination of anomalies is probably inherited as an autosomal recessive trait. A brief literature review of the anomalies or syndromes associated with callosal defects is discussed.
Variability of the Holt‐Oram syndrome in Saudi individuals
Authors: Najjar Haitham , Mardini Mohamed , Tabbaa Rashed , Nyhan William L. , Optiz John M. , Reynolds James F.
Published: June 2005

We studied three families in which patients with the Holt‐Oram syndrome(HOS) had various skeletal abnormalities and congenital heart defects. Two patients had absent thumbs and first metacarpals, hypoplastic radii, and atrial and ventricular septal defects. Patient 2 had pulmonary stenosis, an atrial septal defect, and triphalangeal thumbs. A sister had atrial septal defect and abnormalities of the thumbs; two brothers had abnormalities of the thumbs. The mother had unilateral defect of the thumb with a normal heart. The third patient had tetralogy of Fallot and hypoplastic pulmonary artery. In two families the HOS appeared to be the result of new mutations; in one it was transmitted as an autosomal dominant trait.
Multiple congenital anomaly/mental retardation (MCA/MR) syndrome with Goldenhar complex due to a terminal del(22q)
Authors: Herman Gail E. , Greenberg Frank , Ledbetter David H. , Optiz John M. , Reynolds James F.
Published: June 2005

We present a case of terminal del(22q) with Goldenhar complex including hemifacial microsomia, bilateral epibulbar dermoids, preauricular tags with sensorineural hearing loss, vertebral anomalies, and CNS and renal malformations. The case illustrates causal heterogeneity of the Goldenhar complex and a previously unreportcd associated chromosome deletion.
Fragile‐X mutation and Klinefelter syndrome: A reappraisal
Authors: G. Filippi , V. Pecile , A. Rinaldi , M. Siniscalco
Published: June 2005

To date the concurrent presence of the fragile‐X and the Klinefelter syndromes in the same individual has been found at least 8 times either in the course of screening for the fra(X) condition in mentally retarded males or among the relatives of fra(X) propositi. Given the high frequency of both events in the general population and the heterogeneous approaches with which the above cases were ascertained, it has not been possible to determine unequivocally so far whether the finding is purely coincidental or the expression of some underlying biological relationship. To evaluate the issue, we have screened a large population of institutionalized mentally retarded males for microorchidism, and submitted to a full karyotype analysis and fra(X) testing the patients that were found to have marked bilateral microorchidism. Thus, in a total of 32 microorchidism patients identified among 1115 mentally retarded males, we found 6 to have a 47,XXY chromosome complement in all (or in most) of their cells, with one of them having also the fra(X) marker in 9% of the metaphases examined. In addition, another bearer of the fra(X) marker (but only in 4% of his metaphases) was found among 26 47, XXY mentally normal males ascertained throughout routine cytogenetic analysis of males with microorchidism referred to our genetic counseling unit during the last 10 years. In our laboratory the fra(X) marker has never been observed with such a frequency inatotal of several hundred normal XY males and XX females studied as control cases in the course of previously reported family and population studies. Taken at their face value, the present findings suggest that the incidence of the fra(X) marker among mentally retarded 47, XXY males (and possibly among 47, XXY individuals in general) is several fold greater than the incidence reported, for XY males and XX females. One of the most economical inter pretations of these observations is that heterozygosity for the fra(X) mutation may be a major cause of meiotic X chromosome non‐disjunction. If confirmed, this attractive hypothesis is likely to provide new clues for investigating the biology of the fra(X) mutation and its relationship ‐ if any ‐ with the mechanisms of normal and aberrant meiosis.
The concurrence of Klinefelter syndrome and fragile X syndrome
Authors: Fryns Jean‐Pierre , Berghe Herman Van Den
Published: June 2005

In this paper we report on a third patient with Klinefelter syndrome and fragile X. In the Leuven experience the simultaneous occurrence of both conditions is 1:155 (3 fra(X) positive Klinefelter patients in a total number of 465 fra(X) positive males), a concurrence much higher than expected by chance considering the frequency of both conditions.
The predictive value of dermatoglyphic anomalies in the diagnosis of fra(X)‐positive Martin‐Bell syndrome (MBS)
Authors: Langenbeck Ulrich , Varga Isabell , Hansmann Ingo
Published: June 2005

In a representative group of 160 institutionalized mentally retarded males without Down syndrome, prospective dermatoglyphic‐cytogenetic studies were performed in order to assess the utility of the dermatoglyphic index system of Rodewald [1986] for an efficient ascertainment of patients with Martin‐Bell syndrome (MBS). A negative (abnormal) score was found in 32 men (20 ± 3%), 14 of whom (predictive value: 44 ± 9%) were fra(X)‐positive. This prevalence of 14/160 = 9 ± 2% patients with fra(X)‐positive MBS indicates that in our study most, if not all, MBS patients have been detected by the simple pre‐screening of dermatoglyphics. In the MBS patients, there was no correlation between the dermatoglyphic scores and percentage of fra(X)‐positive cells.
Variable expression of the fragile X syndrome in heterozygous females of normal intelligence
Authors: Wolff Peter H. , Gardner Judith , Lappen John , Paccia Jeanne , Meryash David
Published: June 2005

The cognitive, linguistic and memory functions of non‐retarded fragile X heterozygotes and matched controls were examined by a detailed protocol of neuropsychological measures in order to determine the incidence of specific learning disabilities in this subgroup, and to compare their performance profiles with those of control subjects (mothers of Down syndrome sons). There were no group differences in psychometric intelligence, but the heterozygotes scored significantly lower than controls on most academic achievement tests, as well as on language‐based neuropsychological measures. By neuropsychological criteria, 8 of the 15 heterozygotes, but only one of the controls, exhibited performance profiles consistent with a diagnosis of specific learning disability, and similar to cognitive profiles commonly seen in individuals from the general population with developmental dyslexia.
X‐linked mental retardation with dystonic movements of the hands
Authors: Partington M. W. , Mulley J. C. , Sutherland G. R. , Hockey A. , Thode A. , Turner G.
Published: June 2005

We describe a family with a syndrome of mental retardation, dystonic movements of the hands and dysarthria inherited in an X‐linked recessive pattern. DNA marker studies gave a maximum lod score of 2.11 at θ of 0.00 for DXS41 with a likely localization of the gene to Xpter→Xp21.
Simpson‐Golabi‐Behmel syndrome: Follow‐up of the michigan family
Authors: Opitz John M. , Herrmann Jürgen , Gilbert Enid F. , Matalon Reuben
Published: June 2005

Here we report a follow‐up on a boy born in 1983 into a family with presumed Simpson‐Golabi‐Behmel syndrome and first reported as patient 3 by Opitz [1984] under the designation “Golabi‐Rosen” syndrome. The patient died at 25 months without having attained any measure of psychomotor development or maturation and with a neurologic picture of irritability, increased muscle tone, seizures, deafness and possible cortical blindness. He had a striking facial appearance similar to that of severely affected individuals in the family reported by Golabi and Rosen [1984], with mild hepatosplenomegaly, unusual skin, normal growth, decelerating OFC, and on autopsy a spongiform degeneration of brain stem and cerebrum. Results of all biochemical studies, including those pertaining to GM3 gangliosidosis, were normal.
FG syndrome update 1988: Note of 5 new patients and bibliography
Authors: Opitz John M. , Costa Antonio Richieri‐Da , Aase Jon M. , Benke Paul J.
Published: June 2005

At the eve of its mapping, the pre‐molecular picture of the FG syndrome is heavily biased towards the severe end of the phenotypic spectrum because present knowledge is largely based on propositi. It is an X‐linked, incompletely recessive, complexly pleiotropic syndrome with considerably variable expressivity. Though a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome, severe malformations are uncommon and involve mostly the anus (60%) and non‐colonic GI defects (33%), hypospadias (25%), cleft palate (6%), rarely a congenital heart defect. The complex CNS dysfunctions of congenital hypotonia and all of its sequelae, MR, and occasional seizures, must be attributed to a developmental CNS defect which is rarely demonstrated at pre‐mortem, and which is known to involve agenesis of the corpus callosum in some 25% of appropriately studied patients (mostly propositi). Thus, the diagnosis is largely made on a specific constellation of minor anomalies and mild malformations in a hypotonic boy with severe constipation and a very characteristic facial appearance and behavioral phenotype. In about 1/3 of cases, carrier nianifestations may be detected physically. New hemizygote manifestations seen in this review of 5 new patients include abnormal eruption of teeth, diastasis between upper central incisors, apparent gyneccanastia, cleft lip, and nasolacrimal and helicine fistulae. Only a half hundred or so FG syndrom patients are known, but we suspect the syndrme is much more common than realized, and because of the unfortunate recurrence risk potential, deserves careful consideration in every appropriate case.

RFLP mapping studies are urged in order to aid diagnosis of “mild” cases, and prenatal and carrier detection.
Screening for the fragile X: How many cells should we analyse?
Authors: Tommerup Niels , Laing Susan , Christensen Ib Jarle , Turner Gillian
Published: June 2005

Since nationwide screening for the fragile X would involve the analysis of thousands of individuals within a short period of time, the number of cells, N, which should be analysed is of fundamental importance. When selecting N, the crucial parameter should be the degree of expression of the fragile site in the affected individuals in the population to be screened. However, this degree of expression is not known, and for routine diagnostic purposes, N=100 has been accepted by many centers.

By taking data from two large series of affected males/females with a known degree of expression (one series from New South Wales, one from Belgium), we have estimated the fraction of affected males/females which would have been missed if the two series were rescreened with the analysis of less than 100 cells. Assuming that the degree of expression within these two series is similar to the degree of expression in all affected individuals within the two populations, the results indicate that a reduction of N in a screening program, say from 100 to 50 cells, would reduce the detection rate between 1 and 5%. The reduction would be greater in females than in males, and greater in the Belgian than in the Australian population.
Linkage analysis suggests at least two loci for X‐linked nonspecific mental retardation
Authors: Arveiler B. , Alembik Y. , Hanauer A. , Jacobs P. , Tranebjaerg L. , Mikkelsen M. , Puissant H. , Piet L. Larget , Mandel J. L.
Published: June 2005

Epidemiological studies have suggested that non‐specific X‐linked mental retardation (XLMR) might be at least as frequent as the fragile X syndrome. The identification of all mutations causing XLMR would thus appear of prime importance. In the absence of other clinical signs the problem of genetic heterogeneity is acute. This can be partly overcome by the analysis of large families. We have been able to perform linkage analysis in 3 such families. The condition in family 1 was described as clinically resembling the fra (X) syndrome by Proops et al [1983]: the kindred includes 7 affected males in 3 sibships. Family 2 from Denmark has affected males in 4 generations; however, several affected relatives in this extended pedigree are deceased. Family 3 from France counts 6 affected males in two sibships. The families were analysed with about 25 X‐linked markers. Linkage with markers in Xp22.2–p22.3 was found in family 1: z(θ) = 2.62 at θ = 0.06 for DXS85 (probe 782). Suggestion of linkage was found in family 2 with both the Duchenne muscular dystrophy region (DXS164 in Xp21.2) and with DXS1 (Xq11–q12). In family 3, DXS159 (Xq12–q13) gave a lod score of 2.53 at 6 = 0; results were compatible with localisation of the putative XLMR locus in this family proximal to DXYS1 (Xq21). These data suggest that at least two non‐specific XLMR loci could exist, one in Xp22 and the other in the q12–q13 region.
A new form of hypohidrotic ectodermal dysplasia
Authors: Viljoen Denis L. , Winship Williams S. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 17‐yr‐old young woman with an apparently new tricho‐onycho‐hypohidrotic ectodermal dysplasia. The manifestations include primary interdigital webbing, contractures of fingers and toes, conjunctivitis from narrowing of nasolacrimal ducts, and a small cortical opacity in the lens of the left eye. Psychosocial problems due to the cosmetic appearance are severe. Cause is uncertain.
Developmental delay, short stature, and minor facial anomalies in a child with ring chromosome 16
Authors: Chodirker Bernard N. , Ray Manoranjan , McAlpine Phyllis J. , Riordan Diane , Vust Alice , Pugh Dora , Chudley Albert E. , Opitz John M. , Reynolds James F.
Published: June 2005

We present a girl with ring chromosome 16. Clinical abnormalities included developmental delay, short stature, and minor facial anomalies. Analysis of the glutamatepyruvate transaminase (GPT) phenotype suggests the possible exclusion of the GPT locus expressed in erythrocytes (GPT) from the very distal p13 region of chromosome 16.
Hypomagnesemia masking the appearance of elevated parathyroid hormone concentrations in familial pseudohypoparathyroidism
Authors: Allen David B. , Friedman Aaron L. , Greer Frank R. , Chesney Russell W. , Opitz John M. , Reynolds James F.
Published: June 2005

A 21–yr–old postpartum woman was found to be hypocalcemic and hypomagnesemic with a normal serum immunoreactive parathormone level (hypomagnesemic hypoparathyroidism). She was treated with calcitriol, calcium and magnesium. Two yr later the patient's son presented with tetany, hypocalcemia and the physical changes of pseudohypoparathyroidism. Subsequently, the patient's niece and nephrew were also diagnosed with pseudohypoparathyroidism (low serum calcium, high serum phosphorus, high circulating immunoreactive parathormone). Re‐evaluation of the patient on the above medical therapy showed a normal serum calcium, phosphorus and magnesium levels and an abnormally high serum immunoreactive parathormone level. The patient's magnesium supplementation was discontinued. No change in serum calcium, magnesium or parathormone levels resulted.

We think that this patient demonstrates that hypomagnesemia can mask the laboratory presentation of pseudohypoparathyroidism by suppressing secretion of parathormone and further demonstrates that in pseudohypoparathyroidism the parathyroid gland retains its physiologic response to hypomagnesemia.
Fraser syndrome (cryptophthalmos‐syndactyly syndrome): A review of eleven cases with postmortem findings
Authors: Boyd P. A. , Keeling J. W. , Lindenbaum R. H. , Neri Giovanni , Reynolds James F.
Published: June 2005

Detailed postmortem findings from 11 cases of probable Fraser (cryptophthalmos‐syndactyly) syndrome are reported. Eight cases presented as neonatal deaths, one as a stillbirth, and there were 2 midtrimester fetuses. All of the cases had ocular, otic, digital, laryngeal, and renal abnormalities. Details of the pregnancies and sibship data are also reported. The possibility of prenatal diagnosis for this syndrome is discussed.
Holzgreve‐Wagner‐Rehder syndrome: Potter sequence associated with persistent buccopharyngeal membrane. A second observation
Authors: Legius E. , Moerman Ph. , Fryns J. P. , Vandenberghe K. , Eggermont E. , Opitz John M. , Reynolds James F.
Published: June 2005

Here we present a second example of the syndrome first reported by Holzgreve et al. [1984] in this journal, i.e., Potter sequence with persistent buccopharyngeal membrane type II, Postaxial polydactyly, cleft palate, cardiac anomalies, intestinal nonfixation, and intrauterine growth retardation. This specific complex MCA syndrome is not associated with a detectable chromosome abnormality.
Cleft lip and handedness: A study of laterality
Authors: Yorita Glenn J. , Melnick Michael , Opitz John M. , Reynolds James F.
Published: June 2005

Research on the malformation cleft lip with or without cleft of the palate is complex and may involve studies of etiology, pathogenesis, natural history, and other disease associations. One of the more intriguing areas of study is developmental lateralization. The 3 extant reports of the relationship between laterality of cleft lip and handedness are in conflict. The purpose of the present study is an attempt to resolve the confusion and to explore possible hypotheses that could explain the data.

A random sample of 149 probands with unilateral cleft lip ± palate was ascertained from 2 Los Angeles area hospitals. Laterality of clefting and handedness was determined for each, the former by inspection and the latter by the method of Oldfield [1971]. Information was also obtained on the nuclear family about the number of sibs, presence of clefting, and handedness of he probands' parents. The probability of non‐right‐handedness (NRH) was much greater for probands with left‐sided cleft lip than those with right‐sided cleft lips; this was independent of the proband's sex. The cleft lip laterality in probands was independent of parental handedness, suggesting that the significantly increased frequency of left‐sided clefting and NRH is embryologic in origin and may have a common etiology and/or pathogenesis. Several explanations are proposed and discussed.
Marfan syndrome: Neuropsychological aspects
Authors: Hofman Karen J. , Bernhardt Barbara A. , Pyeritz Reed E. , Opitz John M. , Reynolds James F.
Published: June 2005

We evaluated the neurodevelopmental status and cognitive ability of 30 school‐age children with Marfan syndrome. We found average intellectual (mean full scale IQ = 109.3) and gross motor development. Fifty percent had one or more neuropsychologic deficits: learning disability (LD) (13%), attention deficit disorder with or without hyperactivity (ADD ± H) (17%), neuromaturational immaturity (NMI) (10%), and a performance IQ score different from their verbal score by more than 20 points (30%). Patients with a large verbal‐performance discrepancy, with one exception, scored lower on tests of performance, and particularly low on two subtests, object assembly and coding, compared with the rest of the patients (P < 0.01). The factor most highly correlated with verbal‐performance discrepancy was the severity of joint hypermobility (P = 0.02), which suggests that the depressed performance score was due, in part, to motor incoordination. Children with Marfan syndrome may be prone to neuropsychologic problems; the role of routine screening remains to be tested. Those with hand‐wrist hypermobility seem at particular risk for difficulties with tasks that involve writing and should receive careful evaluation in the classroom. Due to the high risk of aortic dilatation in these patients, if stimulant medications are considered for treatment of ADD ± H, the risk of adverse sympathomimetic effect should be weighed against the potential benefit.
Severe congenital cutis laxa with pulmonary emphysema: A family with three affected sibs
Authors: Van Maldergem L. , Vamos E. , Liebaers I. , Petit P. , Vandevelde G. , Simonis‐Blumenfrucht A. , Bouffioux R. , Kulakowski S. , Hanquinet S. , Van Durme P. , Laporte M. , Ledoux‐Corbusier M. , Reynolds James F. , Neri Giovanni
Published: June 2005

Clinical and morphologic findings in 3 sibs with congenital cutis laxa are presented. A severe urinary malformation in one affected infant is reported in detail. Elevated serum copper concentrations were observed in 2 of the sibs and in the healthy mother. However, the 64Cu uptake of fibroblast cells from tissue culture was not increased. Ultrastructural pathologic findings from skin biopsies have been studied and compared at birth and at age 2 years. The lack of junction between the 2 elastic fiber components was similar. Further evidence for clinical heterogeneity of this disease is stressed.
Recurrence risks for relatives in families with an isolated case of the fragile X syndrome
Authors: Sherman Stephanie L. , Rogatko André , Turner Gillian , Opitz John M. , Reynolds James F.
Published: June 2005

The proportion of sporadic cases among affected males with fragile X‐related mental impairment was reinvestigated in a new sample of family data and compared to previous studies. It was found that the estimate has increased over time from 0 in the original study to 0.24 in the present study. This difference indicated that the correction used for the ascertainment of families in the original study may not have been adequate and that the suggestion that all mothers of affected males are obligate carriers may be wrong. Based on this new information, recurrence risks for relatives in a family with an isolated case of the fragile X or Martin‐Bell syndrome were calculated under different assumptions in order to investigate the effect the effect of (1) the knowledge of the phenotype of ancestors of the proband, (2) the dependence of expression of the mutation on the sex of the carrier parent, (3) the value of the penetrance of mental impairment (MI), and (4) the equality of mutation rates in egg and sperm. The assumptions made for modelling the mutational process had the greatest effect on the recurrence risk in sibs of an isolated case, whereas small differences in penetrance parameters and assumptions based on whether the ancestors were known to be normal or of unknown phenotype made little difference. Recurrence risks for the sibs and first cousins of an isolated case calculated under different assumptions are presented.
The use of early simultaneous percutaneous umbilical blood sampling (PUBS) and amniocentesis for prenatal fragile X chromosome diagnosis
Authors: Butler Merlin G. , Dev Vaithilingam G. , Shah Dinesh , Ulm Janet E. , Wilmot Patrick L. , Shapiro Lawrence R. , Opitz John M. , Reynolds James F.
Published: June 2005

Early simultaneous percutaneous umbilical blood sampling (PUBS) and amniocentesis for prenatal diagnosis were undertaken for the first time in a 17‐week gestation fetus at risk for the fragile X [fra (X)] syndrome. Metaphase spreads from 300 fetal lymphocytes were examined within 5 days following PUBS, while approximately 5 weeks were required for the analysis of 148 amniocytes. The chromosomes were interpreted as normal (46,XX) and the fetus as fragile X‐negative at the time of prenatal diagnosis. This was cytogenetically confirmed after delivery of a healthy term female infant. Our results suggest that early PUBS may become a useful adjunct to amniocentesis because of shorter culture time and earlier diagnosis.
Isochromosome 12p mosaicism (Pallister‐Killian syndrome): Newborn diagnosis by direct bone marrow analysis
Authors: Ward Brian E. , Hayden Melody W. , Robinson Arthur , Opitz John M. , Reynolds James F.
Published: June 2005

A patient who exhibited the phenotype of the Pallister mosaic aneuploid syndrome was cytogenetically diagnosed in the newborn period by bone marrow analysis. A 47,XY,i(12p) karyotype was observed in 100% of the metaphases from direct bone marrow preparations, while phytohemagglutinin (PHA)‐stimulated bone marrow was 23% isochromosome positive. Initially, 10% of metaphases from a peripheral blood culture were isochromosome positive, but at 2 months of age all metaphases examined were cytogenetically normal. Serial fibroblast cultures were 75%, 100%, and 28% positive, respectively. The isochromosome was also present in all metaphases examined from lung tissue and testes. This karyotypic pattern supports a theory that tissue‐limited mosaicism may result from selection due to differing developmental potentials of certain karyotypes in various tissues.
New chromosome aberration: Duplication of a large part of chromosome 4q and partial deletion of chromosome 1q
Authors: Merlob Paul , Kohn Gertrude , Litwin Aviva , Nissenkorn Ilana , Katznelson Mariasa Bath‐Miriam , Reisner Salomon H. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a preterm female infant with multiple anomalies who has a duplication of a large part of 4q and partial deletion of chromosome 1q. Her karyotype was interpreted to be 46,XX,−1, + der(1),t(1;4) (q44;q23 or 24)mat. She is the first patient with an unbalanced translocation involving chromosomes 4 and 1. There is a substantial amount of concordance between the phenotypic features of this patient and those described in the context of partial deletion 1q. The extensive duplication of 4q has no dominant clinical effects in the present infant. These facts support the general concept of much more deleterious effects of deletions versus duplications in human species.
Deletion of terminal portion of 6q: Report of a case with unusual malformations
Authors: Shen‐Schwarz Susan , Hill Lydon M. , Surti Urvashi , Marchese Sandra , Opitz John M. , Reynolds James F.
Published: June 2005

We present the necropsy findings of a 21‐weekgestation male fetus with deletion of the terminal portion of long arm of chromosome 6 [46,XY,del(6)(q23→qter)]. Major anomalies include intrauterine growth retardation, facial anomalies, nuchal cyst, scoliosis, bilateral diaphragmatic hernias, persistent common atrioventricular canal, absent olfactory bulbs and agenesis of corpus callosum. In aberrations of chromosome 6q, patients usually have psychomotor retardation, somatic growth failure, and facial anomalies; nuchal cyst and bilateral diaphragmatic hernias have not yet been described.
Mild Brachmann–de Lange syndrome: Changes of phenotype with age
Authors: Greenberg Frank , Robinson Luther K. , Opitz John M. , Reynolds James F.
Published: June 2005

We present a girl with mild manifestations of the Brachmann‐de Lange syndrome (BDLS) with gradual change of the phenotype. Her findings support the hypothosis of variability of the phenotypic spectrum of the disorder.
Orofaciodigital syndrome type IV: Report of a patient
Authors: Nevin N. C. , Thomas P. S. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a further patient with the orofaciodigital syndrome type IV. The clinical characteristics include lobulated tongue, pseudo‐cleft of lip, pre‐ and postaxial polydactyly of hands and feet, severe talipes equinovarus, mesomelic limb shortness associated with tibial hypoplasia, and severe bilateral deafness. Five similar cases including the present patient are now on record. Autosomal recessive inheritance is likely.
McKusick‐Kaufman syndrome: Report of an instructive family
Authors: Vince John D. , Martin Nicole J. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on two sisters and their brother, all of whom are affected by McKusick‐Kaufman syndrome. This sibship confirms autosomal recessive inheritance and the occurrence of the syndrome in Melanesians. It also demonstrates multisystem involvement in both sexes and illustrates difficulties in the diagnosis and management of hydrocolpos.
A new syndrome with distinct facial and auricular malformations and dominant inheritance
Authors: Simosa Venancio , Penchaszadeh Victor B. , Bustos Tania , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a mother and son with high forehead; elongated and flattened face; arched, sparse eyebrows; short palpebral fissures; telecanthus; long nose and hypoplastic nostrils; long philtrum; microstomia; high, narrow palate; nasal speech; chin dimples; and a highly unusual bilateral auricular malformation. Intelligence and hearing are normal, and there is no “whistling” face or deviation of fingers. Although resembling in some ways the Freeman‐Sheldon syndrome, this phenotype most likely represents a new malformation syndrome, either autosomal dominant or X‐linked dominant.
Congenital pulmonary atresia with intact ventricular septum, tricuspid insufficiency, and patent ductus arteriosus in two sibs
Authors: Eriksen Nancy L. , Buttino Louis , Juberg Richard C. , Opitz John M. , Reynolds James F.
Published: June 2005

Pulmonary atresia comprises only 1% of all congenital heart defects. Counseling the parents on recurrence risks is difficult. We present a rare case of pulmonary atresia in two sibs, along with a review of the literature.
Rhesus sensitization after midtrimester genetic amniocentesis
Authors: Brandenburg H. , Jahoda M. G. J. , Pijpers L. , Wladimiroff J. W. , Opitz John M. , Reynolds James F.
Published: June 2005

In 944 Rh‐negative patients who received rhesus immunoglobulin (anti‐D) following genetic amniocentesis, not a single case of Rh sensitization occurred. Routine administration of a small dose (100 μg) of anti‐D is effective in preventing Rh sensitization after midtrimester amniocentesis.
Sibs with growth deficiency, delayed bone age, congenital hip dislocation, and iridocorneal abnormalities with glaucoma
Authors: Stratton Robert F. , Parker Mark W. , McKeown Craig A. , Johnson Chris P.
Published: June 2005

We report on a brother and sister with short stature, delayed bone age, developmental delay, congenital hip dislocation, and iridocorneal abnormalities with onset of glaucoma at or soon after birth. Results of endocrine evaluation were normal. To our knowledge, no similar pattern of defects has been reported previously.
Survey of neural tube defects in spontaneously aborted embryos
Authors: McFadden Deborah E. , Kalousek Dagmar K.
Published: June 2005

Although variations in the incidence and types of central nervous system abnormalities have been demonstrated between early and late pregnancy, the reason for this finding has not yet been determined.

Among 569 spontaneously aborted embryos, we describe 38 central nervous system lesions, many of which are different from those observed at birth. The importance of correlating morphology and cytogenetic studies in the understanding of pathogenesis of embryonic neural tube defects is emphasized.
Autosomal dominant supravalvular aortic stenosis: Large three‐generation family
Authors: Schmidt Michael A. , Ensing Gregory J. , Michels Virginia V. , Carter Guy A. , Hagler Donald J. , Feldt Robert H.
Published: June 2005

Supravalvular aortic stenosis (SVAS) can be inherited as an isolated autosomal dominant trait or can be a component manifestation of the Williams syndrome. Some consider the Williams syndrome to be due to more severe expression of the gene defect that causes isolated SVAS. We describe a family with isolated SVAS that is the largest thoroughly studied family with this disorder to our knowledge; no patients in this family had Williams syndrome. Five members of this family were reported by Lewis et al. (Dis Chest 55:372–379, 1969). We reevaluated this family and now include examinations of the parents, additional sibs and children of the original 5 patients. Twenty relatives had physical and echocardiographic examinations. In addition, information from outside sources was obtained on 7 relatives not personally evaluated. The SVAS showed marked variability of expression and was not associated with mental retardation or with the facial manifestations of Williams syndrome. We think that previous reports of Williams syndrome reputedly occurring within the same family as isolated autosomal dominant SVAS were inadequately documented. Based on our family and review of the literature, we suggest that isolated SVAS and Williams syndrome represent clinically distinct entities.
Prenatal detection of Roberts‐SC phocomelia syndrome: Report of 2 sibs with characteristic manifestations
Authors: Robins David B. , Ladda Roger L. , Thieme Gary A. , Boal Danielle K. , Emanuel Beverly S. , Zackai Elaine H.
Published: June 2005

We describe 2 sibs with Roberts‐SC phocomelia syndrome. Although an ultrasound scan performed at 13 weeks of gestation failed to identify specific abnormalities, repeat scan at 17 weeks detected tetraphocomelia. Ultrasonography can reliably detect Roberts‐SC phocomelia prenatally; however, serial scans may be needed. Postmortem examination of the proposita confirmed the sonographic findings and also disclosed dysplastic kidneys and ovarian dysgenesis. The degree of phenotypic variation observed between the sibs supports the hypothesis that Roberts syndrome and SC phocomelia represent a single genetic entity.
Lethal form of fibuloulnar A/hypoplasia with renal abnormalities
Authors: Saito Nakamichi , Kuba Akihiro , Tsuruta Toyoshi
Published: June 2005

The present report describes two sibs with lethal acrorenal developmental complex who were products of a nonconsanguinous marriage. Clinical and roentgenologic characteristics did not match any of the known types of fibuloulnar dysostosis. Distinct abnormalities included lethality at birth, facial anomalies, ear anomalies, symmetrical mesomelic shortness of long bones, fibular agenesis, normal vertebrae, oligosyndactyly of phalanges, congenital heart defect, and cystic or hypoplastic kidney. These cases suggest a new lethal form of recessively inherited fibuloulnar dysostosis with renal anomalies.
Hypertrichosis cubiti
Authors: Flannery David B. , Fink Stacey M. , Francis Gary , Gilman Priscilla Ann
Published: June 2005

Hypertrichosis is an unusual but well‐recognized genetic condition. Hypertrichosis may be generalized or limited to specific body areas, in which case it is usually not associated with other anomalies. Five previous cases of hypertrichosis cubiti have been reported, with short stature in 2 sibs being the only other associated abnormalities. We report on a child with hairy elbows, developmental delay, facial asymmetry, and delayed speech with normal parents. Our patient may represent severe expression of the hairy elbow syndrome or constitute apreviously unrecognized syndrome.
Cataracts, alopecia, and sclerodactyly: A Previously apparently undescribed ectodermal dysplasia syndrome on the Island of Rodrigues
Authors: Wallis Colin , Ip François Saw Lan , Beighton Peter
Published: June 2005

An unique autosomal recessive ectodermal dysplasia is present in 5 sibs from the Indian Ocean island of Rodrigues. The main manifestations are total congenital alopecia, bilateral congenital cataracts, and skin changes of the hands and feet including sclerodactyly, hyperkeratosis, contractures, and pseudoainhum formation. The phenotype differs from that of other genetic ectodermal dysplasias and independent syndromic status is probable.
Analysis of chromosome breakage in the Prader‐Labhart‐Willi syndrome
Authors: Butler Merlin G. Md, PhD , Jenkins Bonnie B.
Published: June 2005

Analysis of chromosome breakage with mitomycin C (MMC) and folate‐deficient culture conditions was undertaken on 18 Prader‐Labhart‐Willi syndrome (PLWS) patients (10 with 15q12 deletion [5 females, 5 males; x̄ age = 17.9 yr, range of 0.3 to 40 yr] and 8 without deletion [2 females, 6 males; x̄ age = 18.6 yr, range of 7 to 26 yr]), 21 PLWS parents with an average age of 39.2 yr and a range of 25 to 70 yr (12 fathers [8 fathers of PLWS children with the 15q12 deletion and 4 fathers of PLWS children with normal chromosomes] and 9 mothers [4 mothers of PLWS children with the 15q12 deletion and 5 mothers of PLWS children with normal chromosomes]), and age‐matched control individuals. There was no difference between PLWS patients and control individuals in the number of chromosome and chromatid aberrations in cells grown at 48 and/or 96 hr in either 20 ng/ml or 50 ng/ml of MMC or between the PLWS parents and control individuals in cells grown in 50 ng/ml MMC for 96 hr, although a small increase (P < 0.05) in chromosome breakage was found in cells from the total PLWS parental group compared with control individuals exposed for 48 hr in 50 ng/ml MMC. There was also no significant difference in chromosome fragile site frequency in cells grown in folate‐deficient culture conditions in PLWS patients, their parents, or controls. The average sister chromatid exchange (SCE) frequencies observed in PLWS subgroups (deletion vs. nondeletion), their parents or control individuals were not significantly different. No clustering of chromosome/chromatid breaks or SCEs identified in the proximal long arm was found when compared with the middle or distal long arm regions of the D group chromosomes.
Growth of the foramen magnum in achondroplasia
Authors: Hecht Jacqueline T. , Horton William A. , Reid Cheryl S. , Pyeritz Reed E. , Chakraborty Ranajit
Published: June 2005

Foramen magnum growth curves in achondroplasia and in the general population are presented. The achondroplastic foramen magnum is small at birth, and during the first year it has a severely impaired rate of growth especially in the transverse dimension. This markedly diminished growth results not only from abnormal endochondral bone growth but also because of abnormal placement and premature fusion of the synchondroses. Evaluation of the foramen magnum in achondroplasia should address absolute size of the transverse and sagittal dimensions, shape, and growth centers to determine growth potential of this area.
Detection of a 15q deletion in a child with Angelman syndrome by cytogenetic analysis and flow cytometry
Authors: Cooke A. , Tolmie J. L. , Glencross F. J. , Boyd E. , Clarke M. M. , Day R. , Stephenson J. B. P. , Connor J. M.
Published: June 2005

A proximal 15q deletion, del(15) (q11:q13), was detected in a child with Angelman syndrome by cytogenetic analysis of peripheral lymphocytes. The chromosomes of both parents appeared normal. Flow karyotype analysis carried out on lymphoblastoid cell lines derived from the child and her parents confirmed the presence of a de novo 15 deletion. The estimated size of the deleted segment ranged from 6.1–9.5% of chromosome 15 (approximately 6–9.3 million base pairs). The parental origin of the deleted chromosome could not be resolved by flow cytometry, but cytogenetic evidence suggested that it was derived from the smaller chromosome 15 homologue in the mother.
Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements: Data from United States and Canadian laboratories
Authors: Daniel Art , Hook Ernest B. , Wulf Gary
Published: June 2005

Data on 1,237 prenatal (amniocyte) diagnoses in cases of familial chromosome rearrangements were collated from 79 American and Canadian laboratories. These were added to European data (Daniel et al: Prenatal Diagn 6:315–350, 1986) on 596 reciprocal translocations (rcp) from 71 collaborative laboratories. The total data set was examined for relationships between balanced or unbalanced result and mode of ascertainment, sex of carrier parent, chromosomes involved, and (in cases of reciprocal translocations and pericentric inversions) for potential or actual chromosome imbalance size (% haploid autosome length). Risk rates for unbalanced segregants were markedly dissimilar. These ranged from approximately 50% down to essentially a negligible risk. The risk was approximately 50% for carriers of the following: complex chromosome rearrangements (ccr); insertions (ins); and for 2:2 segregating rcp ascertained by mode 1 (term unbalanced proband) with small imbalance segments. Pooled carriers (either sex) of 2:2 segregating rcp of mode 1 had a risk of 20–25% whereas female Robertsonian (rob) translocation (D;21) carriers and pericentric inversion (pii) carriers of pii with small distal segments had a risk of 10–15%. Pooled 2:2 segregating rcp carriers ascertained by mode 2 (a couple with recurrent miscarriages) and male carriers of rob (D;21) had a risk of 1.5–5%. The risk of unbalanced segregants was 1–2% (in this data) for male and female rob (13; 14) carriers and for pooled pericentric inversion carriers. However, for carriers of most “type” (recurrent breakpoints) pii, for all paracentric inversions, and (as expected) for rob not involving 13 or 21, there were no term unbalanced progeny. For 2:2 segregating reciprocal translocations plots were prepared that could be used to determine broad risk groups for carriers of such rcp. In 3:1 segregating rcp there were 3.3 times fewer male than female carriers, whereas there were 1.3 times fewer male carriers in 2:2 segregating rcp. In 2:2 segregating rcp there is little effect on the fertility of male carriers and risks of unbalanced progeny were found to be equal to those for female carriers, whereas in the 3:1 segregating rcp, risks were much less for male as compared to female carriers. This indicates that 3:1 segregating rcp are more similar to Robertsonian translocations in their greater effect on the fertility of male carriers.
Comments on estimations of risks to translocation carriers
Authors: Stene Jon
Published: June 2005

Two projects for estimation of risks to carriers of reciprocal translocations based on data from more than 1,100 families are compared. The 2 projects differ considerably with regard to the amount of information utilized in the data, the statistical methods used—either standard computer programs or methods specially developed for the data—and the relevance and variety of the obtained results. The comparison shows the strength of utilizing tailor‐made statistical methods for extracting relevant information from available data in human genetics instead of statistical standard methods from general computer programs.
Multivariate analysis of body shape in fragile X (Martin‐Bell) syndrome
Authors: Loesch Danuta Z. , Wilson Susan R.
Published: June 2005

Human body shape measures can be more informative in studies of developmental abnormalities than distances between body landmarks. Such measures were obtained by an appropriate transformation of 34 distances between trunk/limbs and head/face landmarks in 43 men and 72 women with the Martin‐Bell Syndrome (MBS), and in 99 and 103 normal men and women, respectively. The transformation of the original distances was performed by adjusting individual measures for an overall size measure using regression analysis.

Thus obtained body shape variables were used in discriminant analysis in order to obtain unbiased classification probabilities of individuals having the MBS or being normal. The average percent correctly classified male and female individuals was high (93 and 87, respectively). Moreover, the body shape variables were used to obtain shape dimensions by means of principal component analysis. There was no difference between the MBS and normal individuals in the first (most important) principal component (shape dimension). This component represents the relative proportions between trunk and limb lengths and widths, or between midfacial lengths and widths. However, there were appreciable differences in some succeeding components.

The problem of interpretation of shape dimensions as derived from principal component analysis and of their relevance to abnormal development in the MBS individuals is discussed.
Familial distal arthrogryposis with craniofacial abnormalities: A new subtype of type II?
Authors: Moore Cynthia A. , Weaver David D.
Published: June 2005

We report on 5 relatives in 3 generations with an apparent new type of distal arthrogryposis. These individuals have manifestations of type I distal arthrogryposis, but in addition, have craniofacial anomalies that include facial asymmetry, hypertelorism, downslanting palpebral fissures, high nasal bridge, malar hypoplasia, micrognathia, highly arched palate, notched chin, and posteriorly angulated ears. Their intelligence is normal. Although these manifestations preclude us from placing this family in the type I (isolated) distal arthrogryposis category, we also are unable to place them in any of the recognized subtypes of type II distal arthrogryposis. Thus, we think this family may have a previously undescribed form of autosomal dominant type II distal arthrogryposis.
Autosomal recessive form of connatal Pelizaeus‐Merzbacher disease
Authors: Begleiter Michael L. , Harris David J.
Published: June 2005

We report on a brother and sister with the connatal form of Pelizaeus‐Merzbacher disease. This rare degenerative disease of white matter is reported to be transmitted as an X‐linked recessive with an occasional affected female. Some authors have suggested that an autosomal recessive form exists. When this family is analyzed with other families in the literature, both X‐linked and autosomal recessive inheritance must be considered.
Apparent Ruvalcaba syndrome with genitourinary abnormalities
Authors: Bialer Martin G. , Wilson William G. , Kelly Thaddeus E.
Published: June 2005

The Ruvalcaba syndrome is a rare malformation syndrome characterized by skeletal dysplasia, facial anomalies, and mental retardation. We report on a 22‐year‐old woman with severe growth and mental retardation and numerous manifestations characteristic of the Ruvalcaba syndrome. In addition, she has several anomalies not previously described in the Ruvalcaba syndrome, including upslanting palpebral fissures, torus palatinus, hiatal hernia with gastroesophageal reflux, recurrent respiratory infections, pectus excavatum, equinovarous deformity, hypotonia, unilateral renal hypoplasia, an accessory ovary, and atretic fallopian tube. Review of published reports of Ruvalcaba syndrome confirms variability of the clinical and radiographic changes. Findings present in at least 50% of reported patients include mental retardation, short stature, pubertal delay, an abnormal nose (usually beaked) with hypoplastic nasal alae, microstomia with narrow maxilla, thin upper lip vermilion, broad hips, small hands, joint limitation, short fingers and toes, and vertebral abnormalities. Because 5 of the reported patients had renal abnormalities, a renal ultrasound or contrast study is indicated in the evaluation of these patients. Additional reports, particular from multiplex families, will be important to better characterize this syndrome.