bluuebunny/crossref_metadata_2025 huggingface dataset:
Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D‐8) and DXS105 (CX55.7)
Authors: Mulley John , Turner Gillian , Bain Sharon , Sutherland Grant R.
Published: June 2005

Linkage data using the markersF9,DXS105(cX55.7),DXS98(4D‐8) andDXS52(St14) are presented from 22 kindreds segregating with the fragile X. Two‐point linkage analysis was carried out taking into account cytogenetic results and penetrance classes defined by mental impairment status of mothers. Recombination frequencies (θ) corresponding to the maximum z scores (Ẑ) were obtained betweenF9(Ẑ = 3.48, θ= 0.18),DXS105(Ẑ = 5.06, θ= 0.07),DXS98(Ẑ = 4.79, θ= 0.01) andDXS52(Ẑ = 6.44, θ= 0.09) and the fragile X. Recombination frequencies between marker loci in fragile X families are also presented.

These recombination frequencies need to be combined with those from other studies in order to determine the best estimates of map distances for use in genetic counselling, until markers closer to the fragile X, or at the fragile X, can be used. Most potential fra(X) heterozygotes were informative for flanking markers using the above 4 probes. Carrier risks were determined by 3‐point analysis using informative flanking markers, taking into account cytogenetic results. Low level fra(X) expression occurred in 2 probable non‐carriers; emphasising the need for extreme caution in the interpretation of low rates of expression.
Strategy for molecular cloning of the fragile X site DNA
Authors: Warren Stephen T. , Zhang Fuping , Sutcliffe James S. , Peters Jeanne F.
Published: June 2005

Fragile X syndrome is a common form of mental retardation associated with a fragile site on the human X chromosome. We have recently demonstrated that the fragile X chromosome, when isolated within a somatic cell hybrid, often participates in translocations involving rodent chromosome arms. Cytogenetic and molecular evidence strongly suggests that the human breakpoint of these translocations is within the fragile X sequence. Hence,the joining of heterologous DNA (i.e. from two species) may permit the molecular cloning of the fragile X site. We describe here the cloning approach employed to enhance the isolation of interspecific chromosome translocation junctions. The human portion of the translocation junction should be derived from the fragile X site sequence.
Intercalary heterochromatin of Drosophila as a potential model for human fragile sites
Authors: Laird Charles D. , Lamb Mary M.
Published: June 2005

We summarize our proposal that “intercalary hetero‐chromatin” of Drosophila is a useful model for human fragile sites. Comparison with Drosophila site 11A suggests that the normal allele of fragile site Xq27 is a meiotic pairing site.
Fragile‐X mutation proposed to block complete reactivation in females of an inactive X chromosome
Authors: Laird Charles D.
Published: June 2005

I discuss two aspects of my proposal that fra(X) chromosomes exist in two states, imprinted and non‐imprinted: why do males not imprint the fra(X); does the “Sherman paradox” rule out my proposal?
Corpus callosum agenesis, facial anomalies, Robin sequence, and other anomalies: A new autosomal recessive syndrome?
Authors: Toriello Helga V. , Carey John C. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe findings in four children, three of whom are sibs, who appear to have the same, previously undescribed multiple congenital anomaly (MCA) syndrome. The main manifestations include agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, Robin sequence, abnormal ears, redundant neck skin, laryngeal anomalies, cardiac defect, short hands, and hypotonia. The presence of this condition in sibs of each sex suggests that autosomal recessive inheritance is the most likely cause.
Amnion rupture sequence in previable fetuses
Authors: Kalousek D. K. , Bamforth S. , Opitz John M. , Reynolds James F.
Published: June 2005

Amnion rupture sequence is considered an uncommon, sporadic condition among liveborn infants. We have examined 1,010 previable fetuses (9–20 weeks developmental age) to determine the incidence and nature of amnion rupture sequence at this stage of development. We found 18 affected fetuses (15 spontaneous and 3 induced abortions.) with the incidence of 1:56. Eleven fetuses had limb constrictions and amputations only; 7 fetuses also had nonlimb involvement, including disruptions of the craniofacial region mimicking encephalocele, unusual facial clefts, and abdominal defects. In 6 pregnancies, constrictions of the umbilical cord by amniotic bands were the cause of fetal intrauterine death.
Congenital adrenal hypoplasia and selective absence of pituitary luteinizing hormone: A new autosomal recessive syndrome
Authors: Burke B. A. , Wick M. R. , King R. , Thompson T. , Hansen J. , Darrae B. T. , Francke U. , Seltzer W. K. , McCabe E. R. B. , Scheithauer B. W. , Opitz John M. , Reynolds James F.
Published: June 2005

Congenital hypoplasia of the adrenal glands (CHA) is a rare conditions, particularly in the absence of a central nervous system (CNS) anomaly. Two major types of CHA have been described in the setting of an apparently normal CNS and pituitary: a cytomegalic type usually with X‐linked recessive inheritance and a miniature adult type that, when hereditary, is an autosomal recessive trait. Glycerol kinase deficiency (GKD) is an X‐linked recessive trait, and it may be associated with CHA and adrenal insufficiency, presumably because of deletion of adjacent X‐linked loci. We report on three sibling infants, one male and two females, with normal CNS and lethal CHA of the miniature adult type, selective absence of pituitary LH; two of the infants also had glycerol kinase (GK) activity that was decreased but not in the GKD range. Restriction fragment length polymorphism (RFLP) analysis of X chromosome markers located at Xp21‐p22 was carried out on the maternal grandfather, both parents, two of three affected infants, and a living normal brother. The results excluded the X‐linked type of this disorder associated with GKD in this family. Autosomal recessive inheritance is most likely.
Congenital scalp defects with distal limb anomalies (Adams‐Oliver syndrome): Report of ten cases and review of the literature
Authors: Küster Wolfgang , Lenz Widukind , Kääriäinen Helena , Majewski Frank , Opitz John M. , Reynolds James F.
Published: June 2005

We describe one family with 5 affected persons in 4 generations, another family with 2 affected brothers and 3 sporadic cases of the rare syndrome of congenital scalp defects with distal limb deficiency. The manifestations of this syndrome are highly variable. Review of the literature showed 11 families and 19 sporadic cases. In most families the disorder clearly follows an autosomal dominant pattern of inheritance, but in some families with reduced penetrance. Important differential diagnoses are the syndrome of scalp defect and postaxial polydactyly, the syndrome of scalp defect and split‐hand defect, amniotic band sequence, and epidermolysis bullosa dystrophica type Bart.
Familial dilated cardiomyopathy
Authors: Schmidt Michael A. , Michels Virginia V. , Edwards William D. , Miller Fletcher A. , Opitz John M. , Reynolds James F.
Published: June 2005

Idiopathic dilated cardiomyopathy is generally considered a sporadic, nongenetic disorder, and reports of familial cases are often regarded as rare occurrences. Results of the present investigation of 6 families with this disorder suggest that familial forms of dilated cardiomyopathy occur more frequently than previously suspected. The familial nature of the dilated cardiomyopathy was not readily apparent in 3 of these families until thorough family investigations had been performed. The clinical symptoms and age of onset were variable from one family to another and within families. Based on these observations, it is recommended that all persons diagnosed with dilated cardiomyopathy have a thorough review of their family history. If there are any cases of unexplained heart disease, sudden unexpected death or syncopal episodes, further investigations of relatives should be performed. Echocardiography is a convenient noninvasive tool for investigating relatives. Early diagnosis of affected relatives is important for 2 reasons—treatment of significant arrhythmias may prevent sudden unexpected death, and genetic counseling can be provided.
AFP and age screening for down syndrome
Authors: Wald Nicholas , Cuckle Howard , Opitz John M. , Reynolds James F. , Greenberg Frank
Published: June 2005

The availability of maternal serum alpha‐fetoprotein (AFP) values from neural tube defect screening programmes offers the opportunity to improve the effectiveness of screening for Down syndrome. By appropriately combining information on maternal serum AFP and maternal age fewer women would need an amniocentesis to detect a given number of Down syndrome pregnancies or, for a given number of women having amniocentesis, more cases of Down syndrome would be detected than if age alone were used. For example to detect 40% of pregnancies with Down syndrome using AFP and age, 7% of women would need an amniocentesis compared with 11% using age alone. If an amniocentesis and a chromosome analysis together cost $1,000 this is equivalent to a saving of $37,000 per 1000 women screened. The use of AFP as well as age in Down syndrome screening allows patients to be better informed of their risk of having an affected pregnancy. For example, a 35‐year‐old woman has a risk of a Down syndrome term pregnancy of about 1:380, the risk is 1:120 if the AFP level is 0.40 multiples of the normal median (MoM) and 1:1800 if it is 2.50 MoM. Software providing computer assisted test interpretation has been produced to facilitate the estimation of risk and to identify women with positive screening results.
California's experience with low MS‐AFP results
Authors: Lustig Linda , Clarke Susan , Cunningham George , Schonberg Rhonda , Tompkinson Gwynne , Opitz John M. , Reynolds James F. , Greenberg Frank
Published: June 2005

The California AFP Screening Program was developed to offer pregnant women the opportunity to have their pregnancies screened for open neural tube defects (NTD). Because it is unwise to withhold potentially important clinical information about low MS‐AFP results from the screened women and their physicians, follow‐up diagnostic evaluations and counseling were offered to women with low MS‐AFP results in addition to those with high results or positive family histories of NTD.

Between April 7, 1986 and September 30, 1987, over 275,000 women voluntarily participated in the screening program. During the first year of the program 3,939 women were seen for follow‐up evaluations due to low MS‐AFP results. These evaluations occurred at state‐approved AFP follow‐up centers where ultrasonographic dating led to reinterpretation of 35% of the results. Of the remaining 2,552 (65%), 1,940 women (76%) had an amniocentesis. Sixteen Down syndrome fetuses were detected for a yield of 1/121 amniocenteses. Additional chromosome abnormalities included trisomies 18 and 13, Ullrich‐Turner syndrome, (45,X), Klinefelter syndrome (47,XXY) and triploidy. The total yield of significant chromosome abnormalities was 1/78 amniocenteses.
Maternal serum alpha‐fetoprotein screening for down syndrome: Economic considerations
Authors: Swint J. Michael , Greenberg Frank , Opitz John M. , Reynolds James F. , Greenberg Frank
Published: June 2005

The economic consequences of using an index of maternal age and maternal serum alpha‐fetoprotein (MSAFP) screening to indicate risk of Down syndrome (DS) are examined. If DS screening indicated solely by a given maternal age is economically justifiable, then amniocentesis indicated by a DS risk equivalent to that maternal age cutoff, but based on an index of maternal age (for ages below the cutoff) and low MSAFP results, is also economically justifiable. It is concluded that the extant use of MSAFP screening for DS is a move toward the cost‐effective use of scarce resources that can be made available with coordinated planning. However, increased professional and public awareness may result in significant increases in aggregate demand for these services. While MSAFP screening for DS is economically justifiable, there exists some potential for bottlenecks at the aggregate level, and these should be considered in conjunction with recommendations that the technology be adopted on a widespread basis.
Bleeding diathesis in Noonan syndrome: A common association
Authors: Witt David R. , McGillivray Bardbara C. , Allanson Judith E. , Hughes Helen E. , Hathaway William E. , Zipursky Alvin , Hall Judith G. , Opitz John M. , Reynolds James F.
Published: June 2005

The Noonan syndrome (NS) is a multiple congenital anomalies (MCA) syndrome with well‐known manifestations. Excessive bleeding has been described occasionally. We report on 19 patients with NS and a bleeding diathesis. Several different defects are identified in the coagulation and platelet systems occurring singly or in combination. Clinical expression is variable. It is concluded that bleeding diatheses occur in NS at a much higher frequency than previously suspected. Consideration is given to possible relationship to underlying metabolic defects which could explain the diverse nature of the bleeding diatheses and also play a role in the pathogenesis of NS. The variety of bleeding diatheses may also reflect heterogeneity within NS.

NS patients frequently undergo surgery with increased risk of bleeding. Appropriate evaluation and management is discussed. Evaluation of all NS patients and their families for bleeding disorders should provide important information about the frequency and type of bleeding diatheses which occur and perhaps help to clarify the etiology and pathogenesis of NS.
Congenital abnormalities in two sibs exposed to valproic acid in utero
Authors: Chitayat David , Farrell Kevin , Anderson Linda , Hall Judith G. , Opitz John M. , Reynolds James F.
Published: June 2005

Neural tube, craniofacial, and other congenital abnormalities have been described in infants born to mothers with epilepsy who were treated with valproic acid (VPA) during pregnancy. The pathogenetic relationship between the congenital abnormalities and exposure to VPA is not clear. We describe 3 sibs born to a mother with epilepsy. Only the 2 sibs who were exposed to VPA in utero had certain of the characteristic craniofacial changes described in previous reports of children with similar exposure. In addition, the 2 affected children had other craniofacial and skeletal abnormalities which have not been reported previously as teratogenic sequelae of VPA exposure. Many of the minor anomalies present in the 2 affected patients resemble those observed in rhesus monkeys exposed to VPA in utero. This suggests that the abnormalities observed in the 2 children may have been a consequence of intrauterine exposure to VPA.
Duplication of part of 9q due to maternal 12;9 inverted insertion associated with pyloric stenosis
Authors: Yamamoto Yoshifumi , Oguro Noriko , Nara Takahiro , Horita Hideki , Niitsu Naoki , Imaizumi Satohiko , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 9‐month‐old boy who had duplication of the long arm of chromosome 9 [46,XY,−12,+der(12) inv ins (12;9)(p13;q32q13)mat.]. The clinical manifestations of the patient were different from those seen in distal 9q duplication. Pyloric stenosis appears to be common in cases with proximal 9q duplications.
Trisomy 18 with Cantrell pentalogy in a stillborn infant
Authors: Fox Joyce E. , Gloster Elizabeth S. , Mirchandani Raksha , Opitz John M. , Reynolds James F.
Published: June 2005

A 34‐week stillborn infant had omphalocele, agenesis of the sternum and anterior rib cage, membranous diaphragms with eventration of the viscera, ectopia cordis with absence of the pericardium, and congenital heart defect. These findings are consistent with a diagnosis of Cantrell pentalogy. The presence of bilateral clubfeet, spina bifida, hydrocephalus, abnormal ears, and horseshoe kidneys suggested a chromosome abnormality. Chromosome analysis showed trisomy 18. Individuals with manifestations of Cantrell pentalogy deserve cytogenetic evaluation.
Mental retardation, distinct facial changes, short stature, obesity, and hypogonadism: A new X‐linked mental retardation syndrome
Authors: Chudley Albert E. , Lowry R. Brian , Hoar David I. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a 3‐year‐old boy and his 2 maternal uncles with moderate to severe mental retardation, short stature, mild obesity, hypogonadism, a low total finger ridge count, and a distinctive face characterized by bitemporal narrowness, almond‐shaped palperbral fissures, depressed nasal bridge, anteverted nares, short and inverted‐V‐shaped upper lip, and macrostomia. Two other males in this family who had similar facial anomalies and developmental delay died in early infancy and midchildhood. This apparently new disorder is reminiscent of, but distinct from, the Prader‐Willi syndrome, and is likely inherited as an X‐linked recessive trait. Preliminary studies with DNA probes are consistent with an X‐linked locus and permit exclusion of distal Xp and Xq regions as the site of this mutation.
The syndrome of diaphragmatic hernia, abnormal face and distal limb anomalies (Fryns syndrome): Report of two sibs with further delineation of this multiple congenital anomaly (MCA) syndrome
Authors: Moerman Philippe , Fryns Jean‐Pierre , Vandenberghe Kamiel , Devlieger Hugo , Lauweryns Joseph M. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe 2 sibs with the syndrome of diaphragmatic hernia, abnormal face, and distal limb anomalies. Both infants died shortly after birth with severe respiratory distress. Postmortem examination showed gross internal anomalies: Dandy‐Walker malformation, ventricular septal defect, and renal cystic dysplasia. This combination of anomalies, also termed the Fryns syndrome, appears to be a distinct MCA syndrome with variable expression and probable autosomal recessive inheritance.

Prenatal ultrasonographic diagnosis was successful in both patients.
Prevalence of dominant mutations in Spain: Effect of changes in maternal age distribution
Authors: Martínez‐Frías Maria L. , Herranz Inmaculada , Salvador Joaquin , Prieto Luis , Ramos‐Arroyo Maria A. , Rodríguez‐Pinilla Elvira , Cordero José F. , Opitz John M. , Reynolds James F.
Published: June 2005

We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Español de Malformaciones Congénitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay‐Wells, Treacher‐Collins, Robinow, Stickler, Adams‐Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.
Juvenile galactosialidosis in a white male: A new variant
Authors: Chitayat David , Applegarth Derek A. , Lewis Joyce , Dimmick James E. , McCormick Andrew Q. , Hall Judith G. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a 19‐year‐old white male with juvenile galactosialidosis. He presented with hip arthralgia and was found to have facial “coarseness,” corneal clouding, mitral and aortic insufficiency, and hepatosplenomegaly. Ultrastructural studies of skin biopsy and peripheral blood lymphocytes showed membrane‐bound inclusions containing sparse fibrillogranular material. Biochemical analysis showed elevated urinary sialyloligosaccharides and no free sialic acid. Fibroblast enzyme analysis showed low activities of both α‐neuraminidase and β‐galactosidase. To date, most patients with juvenile galactosialidosis have been Japanese. However, unlike those patients, our patient did not have macular cherry‐red spots, neurologic abnormalities, or mental retardation. We speculate that this young man represents a new subtype of juvenile galactosialidosis with a potentially different molecular defect from that of the Japanese variant.
Cerebellar infarction in a patient with Waardenburg syndrome
Authors: Narod Steven A. , Siegel‐Bartelt Jacqueline , Hoffman H. J. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on the occurrence of a basilar artery embolism in a 9‐year‐old boy with Waardenburg syndrome type I. We examined eight other relatives and found that dystopia canthorum was present in six. One of these also had a lumbar meningomyelocele. According to descriptions provided by the grandmother of the propositus, nine other relatives were also affected.
Ultrasonographic prenatal diagnosis and fetal pathology of Langer mesomelic dwarfism
Authors: Evans Mark I. , Zador Ivan E. , Qureshi Faisal , Budev Harish , Quigg Mary Helen , Nadler Henry L. , Opitz John M. , Reynolds James F.
Published: June 2005

In a family at risk for Langer mesomelic dwarfism, we document the onset of disproportionate growth in the second trimester by sonographic biometry. Midt‐trimester pathologic correlation of this condition demonstrates primary changes in the growthplate in the regions of proliferating cartilage and hypertrophic and degenerative chondrocytes.
Direct chromosome analysis from neonatal cord blood
Authors: Day Donald W. , Jalal S. M. , Sinclair‐Worley Leslie , Kukolich Mary , Freeman Mahlon , Sakakini Joseph , Opitz John M. , Reynolds James F.
Published: June 2005

Direct chromosome preparations of neonatal cord blood provides the unique opportunity for rapid chromosome analysis (turnaround time; 6 hr), without the necessity of bone marrow aspiration. Based on 42 samples we confirm the finding of Garnham and Sutherland [1987] for suitability of cord blood for direct chromosome preparation. Procedural modifications are provided for higher yield of cells for chromosome analysis. The procedure may well be of major significance for rapid diagnosis of neonates who suffer from aneusomy.
Prenatal diagnosis and the Canadian collaborative randomized trial of chorionic villi sampling: The physician's view
Authors: Fahy Mellisa J. , Lippman Abby , Opitz John M. , Reynolds James F.
Published: June 2005

Women eligible for the Canadian randomized trial of chorionic villi sampling (CVS) often cite physician influence as a reason for refusing to participate. To measure directly physicians' attitudes to and knowledge of prenatal diagnosis (PND), amniocentesis, CVS, randomized trials, and the Canadian trial, a 3‐page questionnaire was mailed to all registered obstetricians in British Columbia (BC) and in Montreal (Mtl). The overall response rate was 70%. Most physicians thought PND was important and that it was their role to discuss and advise PND to their patients. Physicians were split in their preferences for amniocentesis or CVS (32% vs. 34%); reasons for their preferences paralleled those given by women studied previously by us. Physicians who thought CVS was too experimental, who were hesitant about the trial or who were less likely to discuss the study with patients were older, less likely to have participated in a randomized trial previously and less comfortable with randomization and discussing uncertain risks with patients. Mtl physicians were less aware and more hesitant about the Canadian trial than those in BC. Moreover, Mtl physicians were more likely to consider the ongoing trial inappropriate and too experimental than BC physicians. Because physicians act as “gatekeepers,” educating them about new technologies and about randomized studies is essential for ensuring both participant's access to a new procedure and success of the randomized trial.
Angular homeostasis V: Some issues in genetics, ontogeny, and evolution
Authors: Murphy E. A. , Berger K. R. , Trojak J. E. , Sagawa Y. , Opitz John M.
Published: June 2005

We discuss a provisional model that deals with aspects of normal control of the direction in which cells grow; hence, the organization of structure. The interacting issues of genetics, ontogeny, and phylogeny in relationship to normal development and its defects are addressed. Our main goal is to define a model with a small and sufficient set of conditions that would make it possible to undertake statistically efficient genetic studies of certain congenital defects. But to do so in plausible and heuristic terms, one must address two classical questions: (1) How is the genome translated (or sometimes mistranslated) into a phenotype that is clinically conspicuous and that can be the object of genetic selection, and hence of evolution? (2) Granted that evolution of species occurs in small, rare steps, what is the path that calls for the smallest number of mutations through which ontogenesis could have developed, the intermediate stages being conserved because of actual phenotypic advantage?
Duplication 8q24.2→qter and 15q14→pter resulting from a 3:1 meiotic segregation of a maternal reciprocal translocation
Authors: Kausch Katrin , Haaf Thomas , Schmid Michael , Neri Giovanni , Reynolds James F.
Published: June 2005

We report on a 16‐year‐old female with duplication 8q24.2 → qter and 15q14 → pter resulting from a 3:1 segregation of a maternal balanced reciprocal translocation. This mode of unbalanced segregation could be predicted from Pachytene‐diagram drawing. Most of her clinical manifestations can be related to the proximal 15q trisomy. To our knowledge there is only one previous report of a similar chromosome constitution.
Chromosome findings in twins with early‐onset autistic disorder
Authors: Wahlström Jan , Steffenburg Suzanne , Hellgren Lars , Gillberg Christopher , Opitz John M. , Reynolds James F.
Published: June 2005

In a twin study of autistic disorder, chromosome analyses were carried out in nine pairs of monozygotic (MZ) twins, two pairs of dizygotic (DZ) twins, one set of MZ triplets, one single twin from a MZ pair, and seven single twins from DZ pairs. All but one of the MZ sets were concordant for autistic disorder; all DZ pairs were discordant. Fragile X(q)(27.3) was found in one pair of MZ twins and in MZ triplets, i.e., in 9% of the population with autistic disorder. A marker chromosome of unknown origin was detected in a male twin with autistic disorder from a discordant DZ pair.
Dysmorphogenesis of the mandible, zygoma, and middle ear ossicles in hemifacial microsomia and mandibulofacial dysostosis
Authors: Kay Elizabeth D. , Kay C. Neil , Opitz John M. , Reynolds James F.
Published: June 2005

A review of the anatomical changes in patients with various “first arch” syndromes shows that some anomalies (e.g., micrognathia, ear defects) generally appear together. This study tested the hypothesis that the mandible, zygomatic arch, and middle ear ossicles are a developmental field (i.e., when any of these structures is anomalous, the other two will be also). The hypothesis was tested using data from 25 patients with mandibulofacial dysostosis (MFD) and 40 patients with hemifacial microsomia (HFM).

Analysis of the pooled data showed that the hypothesis of character association was generally supported. However, the medians suggested that different factors probably played a role in determining how these three anatomical structures were associated in MFD and HFM. Errors in chrondrogenesis may have been primarily responsible for the HFM phenotype. Alterations in Meckel and palatoquadrate cartilages would account for the size and shape changes observed in the ossicles and mandible, while changes in cranial base cartilages may explain the changes noted in the zygomatic arch. Since all three structures were equally affected in MFD, it is problematic to use an interference with chrondrogenesis as an explanation for the phenotype.

We conclude that although the mandible, zygomatic arch, and middle ear ossicles appear to form a “developmental field,” the association between structures varies for HFM and MFD. The relatively lesser involvement of the zygomatic arch in HFM than in MFD suggests different pathogeneses for the two diagnostic groups and maybe a useful criterion for judging animal models of HFM.
De novo reciprocal 1p;2q translocation in a child with multiple congenital anomalies/mental retardation syndrome
Authors: Chitayat David , Fagerstrom Carrie L. , Kalousek Dagmar K. , Rootman Jack , Taylor Glenn P. , Hall Judith G. , Opitz John M. , Reynolds James F.
Published: June 2005

A newborn male infant was found to have an unusual pattern of congenital anomalies associated with an apparently balanced de novo reciprocal translocation: 46,XY,t(1;2)(p22;q22). The infant had a previously apparently undescribed multiple congenital anomalies and mental retardation syndrome.
Common fragile sites in couples with recurrent spontaneous abortions
Authors: Schlegelberger Brigitte , Gripp Karen , Grote Werner , Opitz John M. , Reynolds James F.
Published: June 2005

Recently, increased spontaneous chromosome instability was reported in couples with recurrent spontaneous abortions but without constitutional chromosome aberrations. Therefore, we investigated the frequency and distribution of aphidicolin‐induced common fragile sites in couples with recurrent spontaneous abortions and no children and in age‐related control couples. The breakage rate was significantly elevated in the abortion‐prone couples; the women in the abortion couples had an especially higher breakage rate than the control women. Breakpoints cluster to those chromosome regions where common fragile sites have been localized. No preference of a particular common fragile site was demonstrated in the abortion couples. Our findings appear to support the hypothesis of increased chromosome instability in at least some couples with recurrent spontaneous abortions. As long as the nature of aphidicolin‐induced common fragile sites is not completely understood, the significance of these findings remains unclear.
Two brothers with facial anomalies, microcephaly, hypoplastic genitalia, and a failure of psychomotor development
Authors: MacDermot K. D. , Winter R. M. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on 2 brothers from a consanguineous Moslem family with prenatal onset of growth deficiency, microcephaly, hypoplastic genitalia, and convulsions from birth. Phenotypic anomalies consisted of a prominent glabella, arched eyebrows, a low upswept frontal hairline, a small pinched nose, large posteriorly rotated ears with overfolded upper helices, partial camptodactyly, and widespaced nipples. Psychomotor development was absent, and there was marked failure to thrive. Death occurred at ages 21 days and 7 months, respectively. Postmortem examination on one child showed dilated cerebral ventricles and hydronephrosis. Microcephaly was detectable by fetal ultrasound in one brother at 17 weeks of gestation.
Ullrich‐Turner syndrome and anorexia nervosa
Authors: Ohzeki Takehiko , Hayashi Kazuyo , Higurashi Makoto , Hanaki Keiichi , Ishitani Nobuo , Shiraki Kazuo , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 6‐year‐old girl with Ullrich‐Turner syndrome and anorexia nervosa. The diagnosis was made at 6 years and she became anorectic at 14 years. She had been treated with low doses of estrogen just before the onset of anorexia. In spite of remarkable decrease in food intake, her body weight was in the normal range compared to standard weight. Rohrer indices were also normal, probably due to abnormal habitus in individuals with the syndrome. The pathogenetic relationship between this disorder and the hormone treatment in the onset of anorexia nervosa is discussed.
Interstitial deletion of chromosome 22 in a patient with the DiGeorge malformation sequence
Authors: Mascarello J. T. , Bastian J. F. , Jones M. C. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a chromosome 22 deletion in a patient with the DiGeorge malformation sequence as manifested by an interrupted aortic arch, mild thymic hypoplasia, and minor craniofacial anomalies. Although others have reported DiGeorge sequence patients with deletions derived from unbalanced translocations involving the chromosome 22 long arm, the small interstitial deletion described here appears to be unusual for patients with this disorder.
X‐linked cutaneous amyloidosis: Further clinical and pathological observations
Authors: Partington M. W. , Prentice R. S. A. , Opitz John M. , Reynolds James F.
Published: June 2005

A 10‐year follow‐up of a family with X‐linked cutaneous amyloidosis confirmed no more than streaks or spots of brown pigmentation of the skin in females but much more varied and severe manifestations in males. These included neonatal colitis, infantile diarrhea, recurrent respiratory infections, corneal dystrophy, photophobia, unruly hair with a frontal upsweep, dry skin, and mottled, muddy‐brown pigmentation seen first on the inner thighs and spreading diffusely to the buttocks, trunk, and arms. Amyloid was found in the pigmented skin of adults of both sexes but not in children.

An autopsy of a 50‐year‐old man, subject to recurrent pneumonia, confirmed the presence of amyloid in the skin, but it was not found in other organs. Changes in the lungs were those of late‐stage diffuse pulmonary fibrosis.

The pattern of inheritance is X‐linked, but the pathogenesis remains obscure.
Renal tubular dysgenesis: Delayed onset of oligohydramnios
Authors: Swinford Ann E. , Bernstein Jay , Toriello Helga V. , Higgins James V. , Opitz John M. , Reynolds James F.
Published: June 2005

Two premature sibs had Potter sequence and died of respiratory failure within the first day. Ultrasonography at 26 weeks during the earlier of the two pregnancies showed complete absence of amniotic fluid, and the urinary bladder was not visualized. Ultrasound examinations during the second pregnancy showed adequate amniotic fluid at 16 and 20 weeks, with a subsequent reduction in fluid volume. Two older sibs had also died of respiratory failure shortly after birth. Postmortem histopathologic studies showed all four sibs to have severely deficient renal tubular development. However, the presence of numerous glomeruli indicated prolific nephrogenesis. Most of the tubules in sections of cortex had the lectin‐binding and immunohistochemical characteristics of collecting ducts; proximal tubules were not identified by lectin‐binding. Electron‐microscopic examination showed a general absence of differentiated characteristics in cortical tubular epithelium, except that rare tubules contained rudimentary proximal tubular brush borders. Three of the sibs were boys, one a girl. The three children that were studied had normal chromosomes. Two unaffected sibs are alive and well. Neither parent has any clinical evidence of renal disease. These studies support the interpretation that renal tubular dysgenesis is autosomal recessive with pleiotropy. However, the relatively late appearance of oligohydramnios makes early diagnosis difficult, even when the condition is suspected.
A girl with the Pitt‐Rogers‐Danks syndrome
Authors: Oorthuys J. W. E. , Bleeker‐Wagemakers E. M. , Neri Giovanni , Reynolds James F.
Published: June 2005

A severely mentally retarded girl is presented, with symptoms as described by Pitt, Rogers, and Danks (pre‐ and postnatal growth retardation, and unusual facies). Additional manifestations are glaucoma, pre‐auricular pits, and an atrial septal defect.
Inherited diseases in North American Mennonites: Focus on old colony (Chortitza) Mennonites
Authors: Jaworski M. A. , Severini A. , Mansour G. , Hennig K. , Slater J. D. , Jeske R. , Schlaut J. , Yoon J. W. , Maclaren N. K. , Nepom G. T. , Opitz John M. , Reynolds James F.
Published: June 2005

The patterns of migration and the genetic disorders occurring among North American Mennonites are reviewed, and inherited conditions recently recognized in a religious and genetic isolate, the Old Colony (Chortitza) Mennonites, are described. Old Colony Mennonites are of Dutch/ German origin and descend from approximately 400 founding families who settled in the Old Colony, Chortitza (the Ukraine, USSR) in the late 1700s, and then migrated to Canada and Central and South America in the past century. We investigated over 6 generations of a Canadian Old Colony kindred in which there was extensive intermarriage, and in whom 28 individuals developed diabetes mellitus. Insulin‐dependent diabetes mellitus (IDDM) occurred in 14 affected individuals in 10 closely related sibships; the 11 living IDDM patients were all concordant for the immunogenetic marker HLA‐DR4. Fourteen close relatives had other disorders of carbohydrate metabolism, including gestational diabetes and non‐insulin‐dependent diabetes mellitus. Other close relatives had autoimmune diseases, including rheumatoid arthritis, hyper‐ and hypothyroidism, multiple sclerosis, and red cell aplasia. Other inherited diseases, including Alport syndrome, congenital defects, and inborn errors of metabolism were also found in the kindred. In the almost exclusively (99%) Old Colony Mennonite public health district in which the kindred was ascertained, there were multiple cases of Tourette syndrome, of malformations (including congenital heart defects and cleft lip ± palate), and familial clusters of inborn errors of metabolism. We report this Old Colony (Chortitza) Mennonite isolate because (1) there are large familial aggregations of tissue‐specific autoimmune diseases, malformations, inborn errors of metabolism, and of some other conditions whose genetic basis is still unknown; (2) there are multiple cases of rare genetic conditions, (3) we have established a computerized genealogic data base on over 1,000 kindred members as well as a cryopreserved lymphocyte/ DNA bank on over 100 closely related individuals with various genetic conditions; and (4) this religious isolate, which extends across North, Central, and South America, offers an excellent opportunity for studying the epidemiology and molecular genetics of both common and rare inherited diseases.
Syndrome of imperforate oropharynx with costovertebral and auricular anomalies
Authors: Flannery David B. , Opitz John M. , Reynolds James F.
Published: June 2005

This is the second report of a syndromic form of imperforate oropharynx associated with costovertebral and auricular anomalies.
Interstitial long‐arm deletion of chromosome 7 and ectrodactyly
Authors: Tajara Eloiza Helena , Varella‐Garcia Marileila , Gusson Antonio Carlos Tonelli
Published: June 2005

An interstitial deletion of 7q21 was found in a boy with mental retardation, microcephaly, convergent strabismus, micrognathia, genital anomalies, and other findings, including ectrodactyly.
Predictive testing for Huntington disease: II. Demographic characteristics, life‐style patterns, attitudes, and psychosocial assessments of the first fifty‐one test candidates
Authors: Bloch M. , Fahy M. , Fox S. , Hayden M. R. , Reynolds James F.
Published: June 2005

Predictive testing was offered to individuals at‐risk for Huntington disease living within a 100‐mile radius of Vancouver, BC. Ninety‐five at‐risk individuals, representing approximately 12.6% of eligible candidates in this area, have enrolled in its first 16 months. This paper reports on the psychosocial characteristics of the first 51 at‐risk individuals to complete the initial assessment.

Two‐thirds of the candidates are female with a mean age 39.3 years. They derive from higher socioeconomic backgrounds. Reasons for taking the test included planning for the future, concern for their children, and reducing uncertainty. Only 29.4% of candidates would both desire prenatal testing and terminate a high‐risk pregnancy. Results on the SCL 90(R), General Well‐Being, and other scales indicate that the candidates' mental health is representative of the population, but as a group, they are more resourceful. The tests identified individuals who needed further assessment on the basis of previous and current psychiatric functioning and social support. No candidate was a high immediate suicidal risk.

The process of personal assessment has had beneficial effects on personal growth. The self‐selection of a healthy group of candidates emphasizes the need for continued assessment and support as possibly less healthy candidates register for predictive testing programs in the future.
Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis
Authors: Verloes A. , Lambotte C. , Neri Giovanni , Reynolds James F.
Published: June 2005

Three children are described from two sibships. They share infantile ataxia with hypo/aplastic vermis, hepatic fibrocirrhosis, slender‐shaped skeleton, peculiar face, and moderate mental retardation. One of them had a kidney biopsy that showed mild interstitial fibrosis and amyloid deposit, but had no functional impairment. Another suffered moderate proximal tubular acidosis. Two children had unilateral or bilateral choroidal coloboma. This pattern of defects is consistent with a syndrome previously reported in two other sib‐ships. The acronym COACH (Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma, Hepatic fibrocirrhosis) is suggested.
Hypogenitalism in the acrocallosal syndrome
Authors: Temtamy Samia A. , Meguid Nagwa A.
Published: June 2005

We have studied a boy with acrocallosal syndrome and hypogenitalism. He was the offspring of double first cousins. He had unusual facial appearance, postaxial polydactyly with unilateral soft tissue syndactyly of fingers, mental retardation, and absence of corpus callosum. Findings in the present case were compared with those of previously reported cases. Other syndromes associated with agenesis of the corpus callosum must be differentiated. The main differences between the acrocallosal syndrome and the Greig syndrome are outlined with particular emphasis on digital anomalies. The acrocallosal syndrome is an autosomal recessive trait with variable expressivity. Hypogenitalism may be a presenting feature. Positive consanguinity provides further evidence for autosomal recessive inheritance.
Secondary trisomy or mosaic “tetrasomy” 8p
Authors: Robinow Meinhard , Haney Nancy , Chen Harold , Sorauf Thomas , Van Dyke Daniel L. , Babu V. Ramesh , Powell Sandra , Maliszewski William , Guerin Susan , Landers Janes W.
Published: June 2005

We report on two patients with mosaic tetrasomy of 8p[46,XY/47,XY,+i(8p)], a previously unreported cytogenetic anomaly. The first patient had a low percentage of tetrasomic (secondary trisomic) cells in lymphocytes and fibroblasts, an only mildly abnormal phenotype, and a rather benign clinical course. The second patient had a considerably larger percentage of tetrasomic cells in lymphocytes and fibroblasts, and had more severe congenital anomalies that led to his death at 8 months. A characteristic phenotype +i(8p) is suggested but not yet established. The manifestations of these two patients resemble those of mosaic trisomy 8 and mosaic trisomy 8p, with rib and vertebral abnormalities, absent corpus callosum, and enlarged cerebral ventricles.
Chediak‐Higashi syndrome: Prenatal diagnosis by fetal blood examination in the feline model of the disease
Authors: Kahraman M. Müfit , Prieur David J.
Published: June 2005

Chediak‐Higashi syndrome (CHS) is an autosomal recessive disease of humans, mink, cattle, mice, killer whales, cats, and blue and silver foxes. The disease is characterized by incomplete oculocutaneous albinism, recurrent and severe pyogenic infections, a bleeding tendency secondary to a platelet storage pool deficiency, and enlarged granules in many types of cells. Humans with CHS usually die during childhood. It has been suggested that the prenatal diagnosis of CHS should be possible by the demonstration of enlarged granules in neutrophils of fetal blood. We tested this hypothesis using 20 cat fetuses obtained 18 days at prepartum. Two litters (6 fetuses) were from CHS to CHS matings and four litters (14 fetuses) were from CHS male to heterozygous female matings. Fetuses were identified as CHS or phenotypically normal by histologic examination of the size of melanin granules in the ciliary body and by the size of periodic acid‐Schiff‐positive granules in renal tubular epithelial cells. The diameter of the peroxidase‐positive granules in neutrophils of the 15 CHS fetuses ranged from 0.3 to 3.0 μm whereas those of the five normal fetuses ranged from 0.3 to 1.0 μm. All 20 fetuses were correctly classified as CHS or phenotypically normal. These data indicate that examination of the size of fetal blood neutrophil granules can be used to diagnose CHS prenatally.
Angelman syndrome in a daughter with del(15) (q11q13) associated with brachycephaly, hearing loss, enlarged foramen magnum, and ataxia in the mother
Authors: Williams Charles A. , Hendrickson Jill E. , Cantú Eduardo S. , Donlon Timothy A.
Published: June 2005

We report on a 4‐year‐old girl with Angelman syndrome who has an apparent de‐novo del(15) (q11q13) originating from a maternally derived chromosome. Her mother had severe brachycephaly, sensorineural hearing loss, speech impediment, and mild ataxia. CT brain scans showed an enlarged foramen magnum in the mother and daughter but magnetic resonance imaging (MRI) showed no brainstem abnormality in either. This family demonstrates that some Angelman syndrome cases may be dominantly transmitted with variable expression and associated with abnormal or cytogenetically apparently normal chromosome 15.
Duplication of distal 22q
Authors: Abeliovich Dvorak , Maor Esther , Bashan Nava , Carmi Rivka
Published: June 2005

We report on three patients with duplication of distal 22q. One patient is a de novo carrier of the translocation t(21;22) (p13;q11), the other two are offspring of a translocation carrier t(10;22) (q26;q12). The clinical manifestations of these patients demonstrate the variability of the dup(22q) syndrome.
Terminal deletion of the long arm of chromosome 2 in a mildly dysmorphic hypotonic infant with karyotype 46,XY,del(2)(q37)
Authors: Gorski Jerome L. , Cox Beth A. , Kyine Mi , Uhlmann Wendy , Glover Thomas W.
Published: June 2005

We describe a boy with severe hypotonia and minor facial anomalies with a terminal deletion of chromosome 2q (46,XY,del(2)(q37)). Comparison with previous cases in the literature indicates that this particular deletion results in infantile hypotonia, developmental delay, and minor craniofacial anomalies including frontal bossing and micrognathia. The absence of true malformations and few minor anomalies in this patient suggests that indications for obtaining a chromosome analysis from neurologically impaired individuals need to be reevaluated.
A review of phenotype‐karyotype correlations in individuals with interstitial deletions of the long arm of chromosome 2
Authors: Ramer Jeanette C. , Ladda Roger L. , Frankel Carl A. , Beckford Avril
Published: June 2005

We report an infant with del(2)(q31q33). His phenotype is compared with those of the 7 children reported previously with the apparently identical deletion. Nine cases of deletions involving other segments of chromosome 2q are reviewed. Common manifestations of the 2 groups include small size at birth, growth and developmental retardation, cardiovascular malformation, microcephaly, and cleft palate.