bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dubowitz syndrome in a teenager
Authors: Fryns J. P. , Fabry G. , Willemyns F. , Van Den Berghe H.
Published: June 2005

The Dubowitz syndrome has been recognized during the past few years as a new, distinct intrauterine growth‐retardation syndrome with autosomal recessive inheritance. One new patient is presented, a 10½‐year‐old slightly mentally retarded girl.
Mutational mosaicism and genetic counseling in retinoblastoma
Authors: Carlson E. A. , Desnick R. J.
Published: June 2005

Mutations may arise throughout an organism's life cycle. Typically, sporadic meiotic mutations give rise to individuals with all their germinal and somatic cells bearing the mutant gene. These mutations may be amorphs (with full penetrance and expressivity) or hypomorphs (with reduced penetrance and expressivity). Mutational mosaicism, however, involves the origin of mutations occurring during mitosis, whether in the parent at some stage prior to reproductive maturity or in the offspring at some time following fertilization. The phenotypic expression and transmission of these new mutations are dependent on the proportion of cells bearing the mutant gene as well as the location of these cells in somatic and/or germinal tissues. Mutational mosaicism was used as a developmental model to analyze 1,500 sporadic and 179 familial cases of retinoblastoma from the world literature. This model provided an interpretation for the origin, onset, and transmissibility of the sporadic unilateral retinoblastoma cases, which represent over 60% of all retinoblastoma patients. The model also permits a reclassification of all transmissible types of retinoblastoma; based on this classification, more accurate risk figures for genetic counseling can be offered. In addition, mutational mosaicism can be extended as a model to other autosomal dominant and X‐linked mutations.
Cerebroarthrodigital syndrome: A newly recognized formal genesis syndrome in three patients with apparent arthromyodysplasia and sacral agenesis, brain malformation and digital hypoplasia
Authors: Spranger J. W. , Schinzel A. , Myers T. , Ryan J. , Giedion A. , Opitz J. M. , Hall Judith G.
Published: June 2005

We describe three patients with a complex syndrome of apparent arthromyodysplasia, dyscephaly, sacral agenesis, and hypoplastic digits. Cause is unknown, but an environmental cause is suspected on the basis of ergotamine exposure in one case and diazoxide intake in another, together with suggestive similarities to anomalies seen in animals treated with these drugs and to calves with the Australian hydranencephaly/arthrogryposis syndrome caused by Akebane or Aino virus. Pathogenetically the primary defect may be a neural tube‐neural crest dysplasia with multiple secondary and tertiary manifestations and deformities.
The syndrome of ring chromosome 12
Authors: Scribanu Nina , McCullars Eva B. , Baumiller Robert C. , Colon Angel R. , Kaye Celia J.
Published: June 2005

We have studied a 13 month'old girl with failure to thrive, developmental delay, and dysmorphic features. At 13 months, the weight'age was 1 month, length'age was 3 months and head circumference was at the 3rd centile for 3 months. Physical findings were: Epicanthal folds, mildly cupped, apparently low'set ears, highly arched palate, short neck with low hairline, clinodactyly, and single crease of left 5th finger. The modal chromosome number was 46. Trypsin‐G banding identified a ring chromosome 12; Karyotype was 46,XX,r(12)(p13q24).
Autosomal Recessive. Spondylo‐epi‐metaphyseal dysplasia (Irapa type) in a Mexican family: Delineation of the syndrome
Authors: Hernández A. , Ramírez M. L. , Nazará Z. , Ocampo R. , Ibarra B. , Cantú J. M.
Published: June 2005

Three sibs from a Mexican mestizo family affected with a spondylo‐epi‐metaphyseal dysplasia were studied. The clinical, radiological, and genetic findings were similar to those previously described in Venezuelan Indians of the Irapa tribe. The present patients permit confirmation of the syndrome and provide evidence for autosomal recessive inheritance. Genetic drift is postulated.
Holoprosencephaly in a Down syndrome child
Authors: Pi Soo‐Young , Fineman Robert M. , Wing S. Douglas , Grunnet Margaret , Chan Gary , Optiz John M.
Published: June 2005

Gross malformation of the central nervous system (CNS) is rare in Down syndrome (DS). To our knowledge we report for the first time the association of trisomy 21 and holoprosencephaly. Because of the low probability of chance concurrence due to unrelated causes, a causal relationship between these two conditions in the patient must be presumed. The anatomic similarity of the holoprosencephalic defect in this infant to that seen in others with autosomal dominant, recessive, sporadic, or syndromal forms of holoprosencephaly, supports the hypothesis that: (a) this CNS defect is a causally nonspecific developmental field complex (DFC); (b) the increased incidence of such DFCs in the DS represents the result of a nonspecific decrease of developmental homeostasis [Waddington, 1975] due to autosomal aneuploidy.
Preliminary communication: Hairy tip of nose—a new trait in males
Authors: Goswami H. K.
Published: June 2005

Hairy nose tip (HNT) is reported here to be another male sex‐limited trait in man. Out of 1,220 females examined, none demonstrated the trait, whereas the male population frequency is estimated to be 7.35%. The age of onset is 16 years, with a greater prevalence in the age group 46–55, and declining frequency after age 55. Pedigree data do not allow discrimination among several genetic hypotheses.
C‐band polymorphism: Comparison between trisomy 21 cases and mentally retarded controls
Authors: Funderburk S. J. , Klisak I. , Sparkes R. S. , Westlake Joan , Hoehn Holder
Published: June 2005

C‐banding was done prospectively on 50 Down syndrome (trisomy 21) cases and 50 mentally retarded controls. Heterochromatin was quantitated by measuring the lengths of heterochromatin blocks and comparing these segments to the length of the short arm of chromosome 16 for 1, 9 and 16 heterochromatin, and to the total length of the Y chromosome for the Y heterochromatin in the distal long arm. For the first 30 individuals in each group, there was no difference in the mean lengths of C‐band blocks of the 1, 9, 16 and Y chromosomes. For the total sample, there also was no difference between the trisomy 21 cases and controls in the number or size of pericentric inversions involving the heterochromatin blocks of chromosomes 1 and 9. Assuming random segregation of the parental C‐band polymorphisms, this study gives no evidence for an association between such polymorphisms of the 1, 9, 16 and Y chromosomes and nondisjunction of chromosome 21.
Bimodal month of birth distribution in cystic fibrosis
Authors: Brackenridge C. J. , Miller James R.
Published: June 2005

The month of birth of 923 patients in England and Wales dying with cystic fibrosis as an underlying cause was found to be distributed independently of sex and year of birth during 1954–1976. When adjusted for the monthly variations in births in the national population, birth frequencies were bimodally distributed. This confirmed results obtained previously in the Netherlands and Australia. Peak births occurred in late February and August, regardless of whether a single six‐monthly cycle or two annual cycles were assumed. It was not possible to choose the better of these models, each yielding similar parametric estimates.
A boy with congenital malformations and chromosome breakage
Authors: Daneshbod‐Skibba Ghodsi , Therman Eeva , Sahidi Nasrollah T.
Published: June 2005

A patient with increased chromosome breakage and multiple congenital malformations is described. The lack of any apparent quantitative or qualitative disturbance in emopoiesis and adequate number of myeloid and erythroid progenitor cells and the absence of certain clinical features such as webbed neck and absence of dark pigmentation in the patient did not support the diagnosis of the Fanconi pancytopenia syndrome. The cytogenetic studies revealed increased chromosome breakage at G1 phase, a finding which is also at variance with that observed in patients with the Fanconi pancytopenia syndrome.
The ring nature of a tiny supernumerary chromosome fragment
Authors: Hoo J. J. , Drummond Margaret , Parslow M. I. , Chambers Diana , Kaya Celia I.
Published: June 2005

We report a 5½‐year‐old girl with a tiny supernumerary chromosome fragment found in mosaic. The ring nature of the tiny fragment was demonstrated by the detection of the characteristic products of a ring chromosome. The clinical consequence of a ring chromosome and the impact of finding a supernumerary chromosome fragment, especially in the practice of prenatal chromosome diagnosis, are discussed.
Two conceptions in a 45,X woman
Authors: Kohn G. , Yarkoni S. , Cohen M. M. , Opitz John M.
Published: June 2005

We present a 31‐year‐old woman with a 45,X chromosome constitution who had had two miscarriages. This report brings to 11 the number of presumably non‐mosaic Ullrich‐Turner syndrome patients who have achieved pregnancy. A review of the literature indicates an increased incidence of chromosome abnormalities and a high rate of fetal death in offspring of such patients. However, in light of the fertility in these patients, genetic counseling should be reevaluated and perhaps amniocentesis recommended in successful pregnancies.
Congenital lethal metaphyseal chondrodysplasia: A newly recognized complex autosomal recessive disorder
Authors: Sedaghatian M. R. , Opitz John M.
Published: June 2005

This is a report of two brothers, born within a year of each other, with a similar skeletal disorder of severe congenital metaphyseal involvement, mild rhizomelic shortness of upper limbs, and mild platyspondyly. Both died at three days of cardio‐respiratory insufficiency, but only one had ante‐mortem lab tests which showed low calcium, high phosphorus, and high alkaline phosphatase levels attributed to a renal defect. On autopsy this same infant was found to have pulmonary, renal and adrenal hemorrhage, and subendocardial myocarditis and myocardial necrosis. The pathogenetic relationship between these manifestations is presently unclear; however, since parents are normal and recently had an affected baby girl, it is presumed that this disorder is an autosomal recessive trait.
Amniotic 17‐α hydroxyprogesterone and HLA typing for the prenatal diagnosis of 21‐α hydroxylase deficiency — congenital adrenal hyperplasia
Authors: Rosenmann Ada , Schumert Zewijah , Theodor Rachel , Cohen Tirza , Brautbar Chaim
Published: June 2005

We have investigated a family with one child affected with congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency. Prenatal determination of 17‐α hydroxyprogesterone (17OHP) in amniotic fluid (AF) and HLA typing of amniotic fibroblasts from a pregnancy at risk showed that the fetus was not affected.

A healthy cousin with HLA haplotypes identical to those of the proposita (only one being identical by descent) had a normal plasma level of 17OHP.

The prenatal diagnosis of a fetus affected with 21‐hydroxylase deficiency CAH may be established by the determination of 17OHP in AF. This is a relatively quick procedure that can be confirmed by the HLA genotype, and is mandatory in families with a parent homozygous for an HLA haplotype and in certain recombinant haplotypes in the fetus.
Frequency of new mutants among boys with Duchenne muscular dystrophy
Authors: Bucher K. , Ionasescu V. , Hanson J. , Optiz John M.
Published: June 2005

Haldane's rule states that one‐third of the cases of an X‐linked recessive lethal should represent new mutations. This rule is derived under the assumptions that there is equilibrium between mutation and selection, that mutation rates in ova and sperm are equal, and that heterozygous and homozygous normal women have the same fitness. To test this rule for Duchenne muscular dystrophy (DMD), we have examined the mothers of 55 boys with DMD (16 familial and 39 isolated cases) and classified them as carriers or noncarriers on the basis of measures of ribosomal protein synthesis (RPS). Of the 55 mothers, only nine (16.4%) are classified as noncarriers, a figure significantly different from the expected one‐third. When the analysis is limited to the 39 mothers of isolated cases, 23.1% (9/39) are classified as noncarriers, still significantly different than expected under Haldane's rule. Violation of any of the assumptions under which Haldane's rule is derived could lead to deviations from the expected one‐third new mutants. We find the most likely explanation to be a higher male than female mutation rate. This is supported also by the finding that maternal grandfathers in whom a mutation occurred had higher mean age at birth of the carrier daughter (33.7 ± 1.6) than did the general population or intrapedigree controls (29.5 ± 1.3).
The Dubowitz syndrome: Further observations
Authors: Orrison William W. , Schnitzler Eugene R. , Chun Raymond W. M. , Optiz John M.
Published: June 2005

An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal retardation, microcephaly, sparse hair, toe syndactyly, and characteristic facial appearance is now recognized as the Dubowitz syndrome. Five addition additional cases of the Dubowitz syndrome are reported, including 2 with documented vascular abnormalities.
Short rib‐polydactyly syndrome, Majewski type
Authors: Chen Harold , Yang S. Samuel , Gonzalez Enrique , Fowler Marjorie , Al Saadi A. , Optiz John M.
Published: June 2005

A term infant had dwarfism with characteristic skeletal and extraskeletal changes of the short rib‐polydactyly syndrome type 2 (Majewski). The skeletal changes included extremely short horizontal ribs, extreme micromelia with disproportionately short ovoid tibiae, and pre‐ and post‐axial polydactyly. Microscopically, cartilage showed markedly stunted and disorganized endochondral ossification. Extraskeletal manifestations were hydrops, cleft lip, malformed larynx with hypoplastic epiglottis, pulmonary hypoplasia, glomerular and renal tubular cysts, ambiguous genitalia, pachygyria and small cerebellar vermis. Parental consanguinity supports the hypothesis of autosomal recessive inheritance of the condition.
GENFILES: A computerized medical genetics information network. I. An overview
Authors: Loughman William D. , Mitchell Joyce A. , Mosher Douglas C. , Epstein Charles J.
Published: June 2005

GENFILES is a comprehensive computer information network to serve research, service, and administrative needs in medical genetics. Four major databases contain detailed information generated by the cytogenetics laboratory, the prenatal diagnosis program, the diagnostic and genetic counseling clinics, and the human cell culture facility. Unique aspects are the use of RAMIS, a commercial database management system, and of microprocessor computers as “intelligent” terminals with significant data‐handling capabilities. All databases are on‐line in a directly accessed large timesharing computer. The system, which has been designed, controlled, and maintained by regular genetics staff, is an easy to use, moderate‐cost tool well suited for use as a regional clinical genetics information system.
Neural tube malformations: Complex segregation analysis and recurrence risk
Authors: Pietrzyk Jacek J. , Optiz John M.
Published: June 2005

A sample of 223 families with at least one child with anencephaly and/or spina bifida was ascertained in Southern Poland, where the incidence of neural tube malformations is 0.92/1,000. The recurrence risk in proband's sibs was 3.4%. The calculated heritability (h2) was 76%, implying a substantial contribution of genetic factors to the cause of neural tube defects. Complex segregation analysis was applied in an attempt to discriminate between the hypothesis of a single locus and that of quasi‐continuity under multifactorial inheritance. The results excluded the hypothesis of dominant inheritance with full penetrance. The hypothesis of the two‐allele model (at a single locus) fit the data with the same degree of exactness; however, for all hypotheses the estimated penetrance was low, and the phenocopy frequency was high. Less accurate conformity was observed for the multifactorial hypothesis. In view of very low penetrance and high frequency of phenocopies in single locus hypotheses and the finding that empirical data gave better support to the multifactorial model, the differences in χ2 values should not be viewed as sufficient to discriminate between single locus and multifactorial models. The recurrence risks, assessed in the complex segregation analysis, showed an increase together with the growing number (r) of affected children. For constant r the recurrence risks decreased in successive pregnancies. Although discrimination between the mendelian and multifactorial inheritance models was incomplete, the risk values obtained can be employed in genetic counseling.
Duplication 8p syndrome: Studies in a family with a reciprocal translocation between chromosomes 8 and 12
Authors: MorenoFuenmayor H. , Meilinger K. L. , Rucknagel D. L. , Mohrenweiser H. L. , Chu E. H. Y. , Optiz John M.
Published: June 2005

We report a family in which six individuals were carriers of a translocation between chromosomes 8 and 12. The balanced carriers had a chromosome constitution: 46,XX or 46,XY,t(8;12)(021;p13). Six individuals in five generations were mentally retarded. Three of them were examined; their chromosome constitution was 46,XX or 46,XY,der(12),t(8;12)(p21;p13); thus they had a duplication of 8pter→8p21 and possible deficiency of 12pter→12p13. The activities of the enzymes that are coded by genes on 8p (glutathione reductase, GSR, E.C. 1.6.4.2.) and 12p (triosephosphate isomerase, TPI, E.C. 5.3.1.1.; lactate dehydrogenase‐B, LDH‐B, E.C. 1.1.1.27.; and glyceraldehyde‐3‐phosphate dehydrogenase, G3PD, E.C. 1.2.1.12.) were normal in these individuals. These findings helped in interpreting the position of the break points in the respective chromosomes. The phenotypic findings in our patients are discussed.

Segregation analysis indicates no significant variation from a 25% recurrence risk for each of the possible genotypes in the offspring of balanced carriers.
Prenatal genetic diagnosis and elective abortion in women over 35: Utilization and relative impact on the birth prevalence of Down syndrome in Washington State
Authors: Luthy David A. , Emanuel Irvin , Hoehn Holger , Hall Judith G. , Powers Ellen K. , Optiz John M.
Published: June 2005

We have examined the relative contributions of a population‐based antenatal detection program and unrestricted elective abortion used by women 35 years old and over in Washington State and King County for 1976–1977 to the declining birth prevalence of Down syndrome (DS). The amniocentesis/live birth (LB) ratio for women 35 years old and ove was 20.5/100 LBs for King County and 11.7/100 LBs for Washington State in 1977. For the state in 1976, abortion ratios/1,000 LBs were 571 for women 35 to 39 years old and 1,096 for women 40 years old and over.

Based on the total Washington State data, elective abortion has a greater impact on averting DS births than does the antenatal detection program. The impact of elective abortion appears to be related to its disproportionate use by women 35 years old and over compared to their contribution to the population of of LBs.
Significance of phenotypic and chromosomal abnormalities in X‐linked mental retardation (Martin‐Bell or Renpenning syndrome)
Authors: Jennings M. , Hall J. G. , Hoehn H. , Herrmann Jürgen
Published: June 2005

With the exception of macro‐orchidism, three families with X‐linked mental retardation showed diagnostic concordance of clinical features among the affected males. Since macro‐orchidism was a variable feature among the otherwise identically affected males in one family, we question the existence of a separate entity of X‐linked mental retardation characterized only by testicular enlargement. The X chromosome marker of Lubs was expressed, under the culture conditions of Sutherland, in lymphocytes of the affected males of two families, one with and the other without megalotestes. Two affected members of the third family, with megalotestes, did not show the marker. Telomeric structural changes similar to the mar(X) (qter) formation were found on certain autosomes, notably, chromosome 6 in some of the affected males, potential and obligate carrier females, and in both related and unrelated normal males. These autosomal markers appear to represent a nonspecific response to either in vivo or in vitro folate deficiency. Caution against premature introduction of this test for prenatal diagnosis, in the face of current ignorance regarding diagnostic specificity, is urged.
X‐linked mental retardation with macro‐orchidism and marker‐X chromosomes
Authors: Martin Renée H. , Lin C. C. , Mathies Barbara J. , Lowry R. Brian , Optiz John M.
Published: June 2005

The family of 2 men with X‐linked mental retardation was investigated for the presence of the marker‐X chromosome and macro‐orchidism. Lymphocyte cultures were set up in media F‐10 and 199. Chromosomes were G‐band‐stained and slides coded for blind analysis. Marker‐X chromosomes and autosomal gaps were seen only in cultures prepared with medium 199. Autosomal gaps were seen in all family members and controls. The marker‐X chromosome was present in affected male (3% and 15.5%) and female family members (0.5%–6.5%) but not in controls or a normal male family member. Bilateral macro‐orchidism was present in 1 affected male and unilateral macro‐orchidism in the other. Both had normal penile measurements. The replication pattern of the marker‐X chromosome was studied in 1 woman by BrdU labelling. BrdU decreases the frequency of marker‐X expression. As the marker‐X chromosome was the late‐replicating X in 9/20 cells, it appears that there is no preferential inactivation of the marker‐X in this woman.
X‐linked mental retardation: A study of 7 families
Authors: Jacobs Patricia A. , Glover Thomas W. , Mayer Martha , Fox Patricia , Gerrard John W. , Dunn Henry G. , Herbst Diana S. , Optiz John M.
Published: June 2005

Seven families with X‐linked mental retardation (MR) have been studied clinically and cytogenetically. All affected males in six of the families were found to have a fragile site on Xq in a number of their peripheral lymphocytes. The fragile site was not seen in any of the affected males in the seventh family. The affected males in the six families with the fragile X had a syndrome characterized by a variable degree of MR, macro‐orchidism, a characteristic repetitive, jocular speech, normal body proportions, and large jaws and ears.

The fragile X chromosome could only be detected in a proportion of female carriers and its frequency in females was found to be correlated with their mental status and to be inversely correlated with their age.
Fragile sites in human chromosomes II: Demonstration of the fragile site Xq27 in carriers of X‐linked mental retardation
Authors: Howard‐Peebles Patricia N. , Optiz John M.
Published: June 2005

Demonstrating the Xq27 fragile site in men with X‐linked mental retardation and in obligate carriers is a continuing problem. I report two additional families with this disorder (Families F and G) and present cytogenetic data on females from four families (D–G). These data and those previously published suggest that there are two types of families in regard to fragile Xq expression in carrier females. One type shows no apparent phenotypic effect in the female and the demonstration of the fragile Xq becomes more difficult with increasing age, whereas the second type is associated with some phenotypic effect (ie, reduction in mental ability), and the fragile Xq can be demonstrated regardless of age.
Double trisomy 48,XXX,+18 in a newborn
Authors: Rosenfeld Warren , Verma Ram S. , Jhaveri Ramesh C. , Salazar Delfor , Dosik Harvey
Published: June 2005

We report the 6th case of double trisomy X and 18, ie, 48,XXX,+18. The infant lacked overlapping fingers, simian creases, and structural heart disease and is alive at 275 days. Two X chromosomes were late replicating. Anomalies of the hands and kidneys involved only the right side in the present case; review of the five previous cases of 48,XXX,+18 also showed that anomalies of kidneys, hands, and ears affected predominantly the right side in three patients.
Psychological aspects of genetic counseling: Analysis of a transcript
Authors: Kessler Seymour , Antley Ray M.
Published: June 2005

A transcript of a genetic counseling session is presented and discussed by 2 separate readers. The style of counseling emphasized content material at the expense of process. The counselor avoided or evaded affective issues and thus limited his ability to clarify the current attitudes and beliefs of the counselees as well as to identify their future needs. However, one emphathic intervention did have an important impact on changing the tone of the session. The issues of directiveness and neutrality were examined in light of the process of the session. The counselor appeared to be largely nondirective in his advice‐giving and ostensibly neutral in his educational approach. Nevertheless, his overall counseling strategy seemed to be aimed at persuading the counselees to agree to have the amniocentesis procedure. The need for more information on what actually occurs in the course of genetic counseling is underscored.
Minor manifestations in preaxial polydactyly type 1 and Poland complex
Authors: Halal Fahed , Opitz John M.
Published: June 2005

We report three unrelated patients: two (patients 1 and 3) with preaxial polydactyly type 1 (PPT1), and one (patient 2) with PPT1 and Poland complex, and previously undescribed minor manifestations in the parents. The mother of patient 1 has camptodactyly with mild ulnar deviation of the distal phalanx of left thumb. The mother of patient 2 has symmetrical minor changes of both hands: mild camptodactyly of digits 4 and 5; mild clinodactyly of right 5th digit; absent or hypoplastic DIP flexion creases of digits 2, 3, 4 and 5; and tight skin around the middle phalanx of the 4th fingers. The mother of patient 3 has mild camptodactyly of the proximal phalanx of the thumbs.
Coffin‐Lowry syndrome in sibs
Authors: Mattei J. F. , Laframboise R. , Rouault F. , Giraud F. , Opitz John M.
Published: June 2005

The authors report the Coffin‐Lowry syndrome in two sibs and suggest autosomal recessive inheritance of the condition in this family.
Duplication 3p syndrome: Report of a new case and review of the literature
Authors: Charrow Joel , Cohen Maimon M. , Meeker Diana , Opitz John M.
Published: June 2005

A review of the 17 previously reported cases of duplication 3p and study of a new patient who has a duplication of the chromosome segment 3p21→pter show a remarkably consistent phenotype among these patients and suggest some generalizations about prognosis. The manifestations include low birth weight, short stature, microcephaly, characteristic “square” face with temporal indentations, hypertelorism and/or telecanthus, epicanthus with a broad nasal bridge and large nasal tip, and down‐turned corners of the mouth. Cleft lip/palate and eversion of the lips are common. The jaw is typically small and receding and the neck short. Congenital heart disease, gastrointestinal malformations, abnormalities on intravenous urography, and defective masculinization of the male infants are frequently observed. A predominance of whorls is present on the fingers. Nearly half of the cases died before 6 months. All affected children surviving beyond 1 year have been mentally retarded.
Cohen syndrome: Further delineation and inheritance
Authors: Kousseff Boris G. , Opitz John M.
Published: June 2005

Four sibs, 2 males and 2 females, were found to have the Cohen syndrome. All had moderate mental retardation, microcephaly, hypotonia, and narrow hands and feet with elongated fingers and toes; 3 were short of stature (2.0–3.5 SD below the mean) with weight between 10th and 50th centile and truncal obesity. Most of the facial characteristics of the syndrome were present: exotropia, prominent ears, short philtrum, and high nasal bridge. Each manifestation varied in severity from one sib to the other. The younger girl also had rheumatoid arthritis. Mild delay of puberty was described in 3 of the sibs. However, one of them has delivered a male infant with normal appearance whose psychomotor development has been normal (as of 9 months). No endocrine problems were documented in the sibship. All patients had normal chromosomes.

The data on this sibship support the hypothesis of autosomal recessive inheritance of the Cohen syndrome. Microcephaly and short stature should be stressed as frequent manifestations of the syndrome. The variable expressivity, even among sibs, may be responsible for the paucity of reports on the mildest froms of the Cohen syndrome.
Nerve deafness, optic nerve atrophy, and dementia: A new X‐linked recessive syndrome?
Authors: Genes Peter K. A. , Opitz John M.
Published: June 2005

A new syndrome characterized by sensorineural hearing loss (beginning in early infancy), progressive optic nerve atrophy, and dementia (beginning in adult‐hood) is described in 3 males in the same family. This is probably an X‐linked recessive trait.
Genetic linkage analysis of dermo‐distortive urticaria
Authors: Epstein Paul A. , Kidd Kenneth K. , Sparkes Robert S. , Opitz John M.
Published: June 2005

We have described a new hereditary physical urticaria, dermo‐distortive urticaria (DDU) [1]. In an attempt to map the locus of this autosomal‐dominant disorder and to further characterize it, a linkage analysis with 18 genetic markers was done. Close linkage of DDU with TCII, GALT, Gc, Fy, Kell, and Se was excluded. The most significant positive lod score was for the MNSs blood antigen system, which has a maximum lod score of 1.09 at θ = 0.24 for all 28 family members who were typed. Although close linkage with DDU is not demonstrated at any marker, this study illustrates how linkage analysis may prove to be of value in the characterization of newly discovered heritable disorders.
Schisis‐association
Authors: Czeizel Andrew , Opitz John M.
Published: June 2005

The neural tube defects (anencephaly, encephalocele, spina bifida cystica), oral clefts (cleft lip ± palate, posterior cleft palate), omphalocele, and diaphragmatic hernia associate with one another far more frequently than at the expected random combination rates. The combination of other abnormalities does not exceed the expected rate. Thus, two or more combinations of schisis‐type abnormalities without other defects were treated as a provisional entity. The schisis‐association is practically a lethal abnormality. It occurs more often in girls (sex ratio: 0.33), in twins (4.6%), in breech presentations (13.7%), in association with lower mean birth weight (1,931 gm), and in association with a shorter gestation period (36.4 weeks). Mothers of affected children have a significantly higher miscarriage rate; occurrence of schisis‐type abnormalities was found in 3.7% of the sibs of index patients. However, except for one, the sib‐occurrences of schisis abnormalities were isolated neural tube defects or oral clefts.
Heterozygote detection in fabry disease utilizing multiple enzyme activities
Authors: Sheth Kumudchandra J. , Good Thomas A. , Murphy Jerome V. , Opitz John M.
Published: June 2005

In Fabry disease, as in other X‐linked traits, identification of all heterozygotes is difficult. Reduced plasma α‐galactosidase activities will correctly identify 60–70% of the carriers. The identification rate improves when an α/β‐galactosidase activity enzyme ratio is used. We measured α‐galactosidase activity in reference to several other enzyme activities, β‐galactosidase, β‐hexosaminidase, and α‐fucosidase in plasma and leukocytes from 22 suspected and 9 obligate carriers from 4 kindreds of Fabry disease patients. Utilizing such ratios or various combinations of ratios in plasma we have correctly identified the carrier state in 91% of heterozygotes. Leukocyte α/β‐galactosidase identified one more female than leukocyte α‐galactosidase activities alone. We recommend the use of such multiple biochemical tests to identify carriers of Fabry disease.
The usefulness of NOR and RFA banding in prenatal diagnosis: A case report
Authors: Sciorra Leonard J. , Rajendra Barathur , Cummings Emilie , Ekblom Linda , Lee Ming‐liang , Opitz John M.
Published: June 2005

Prenatal chromosome analysis of amniotic cells showed a male fetus to carry an unusual marker D chromosome containing extra genetic material on the short arm, which could be interpreted as a possible t(D;G) or t(D;Fq) unbalanced translocation using non‐branded preparations or a routine GTG band method. Analysis of this marker by NOR and RFA banding and parental chromosome studies showed the marker to be an unusual variant of the satellited area of chromosome 15, with no associated phenotypic anomalies. The usefulness of NOR and RFA banding as aids in chromosome identification in prenatal diagnosis is discussed.
Duplication 3q: Severe manifestations in an infant with duplication of a short segment of 3q
Authors: Rosenfeld Warren , Verma Ram S. , Jhaveri Ramesh C. , Estrada Raul , Evans Hugh , Dosik Harvey , Opitz John M.
Published: June 2005

A patient with duplication of a short segment of 3q (3q21→26) without apparent deletion of 3 or of other chromosomes provided a further opportunity to study manifestations of this abnormality. The proposita had a broad nasal bridge, anteverted nostrils, webbed neck, and clinodactyly V in addition to congenital heart disease, limb abnormalities, cleft palate, and severe developmental delay. The infant did not have the hirsutism and synophrys present in other cases.
Genetic transmission of serum IgE levels
Authors: Blumenthal Malcolm N. , Namboodiri Kadambari , Mendell Nancy , Gleich Gerald , Elston Robert C. , Yunis Edmund , Opitz John M.
Published: June 2005

Genetic aspects of IgE levels were studied in three large pedigrees, many of whose members had atopic sensitivities to ragweed. Data on 184 persons (80 M, 104 F) were analyzed by the methods of Elston and Stewart after logarithmic transformation and appropriate adjustment for sex and age effects. Several modes of transmission were fitted to the data. The environmental model (of equal transmission frequency for all genotypes) clearly did not fit the data (χ2 23.03, df 3); this suggested a strong hereditary involvement in IgE distribution. High IgE levels being determined by a dominant allele gave the best fit among the hypotheses examined in pooled data. Under a pure polygenic model, the estimated heritability was 49.5%. Using a mixed model of major gene and polygenic transmission (in an analysis which approximates, but is biased toward inflating the major gene component) polygenic inheritance was found to be 11%, but has no significant improvement over the major gene model. When families are analyzed separately, there was evidence of significant heterogeneity among families. The genetic picture was blurred, with one family favouring recessive inheritance of high IgE levels, one with no clear mode, and the third leaning slightly in favor of dominant inheritance. This suggests that the mechanism is not as simple as was thought and that there may be either two alleles or one gene involved in the determination of IgE levels. The findings are consistent with IgE levels being genetically determined with heritability estimated to be about 50%.
Familial pericentric inversion of chromosome 8
Authors: Sujansky Eva , Smith Ann C. M. , Peakman David C. , McConnell Thomas S. , Baca Patricia , Robinson Arthur , Opitz John M.
Published: June 2005

Eight children from seven presumably unrelated families were identified independently as having an unbalanced recombinant chromosome resulting in the presence of extra material on the short arm of a chromosome 8. Parental chromosomes were analyzed, and one member of each couple (four fathers and three mothers) was found to carry a pericentric inversion of a chromosome 8 [inv(8)(p23q22)]. The propositi had an unbalanced recombinant chromosome [rec(8),dup q,inv(8)(p23q22)]. The affected infants all had developmental delay, congenital heart disease, and unusual appearance. A common origin of the pericentric inversion was suggested because of geographic location and Mexican—American ancestry of the seven families.
On genetic screening of donors for artificial insemination
Authors: Fraser F. Clarke , Forse R. Allan , Opitz John M.
Published: June 2005

Reliable information on the frequency of birth defects in children conceived by artificial insemination is lacking and should be collected. Genetic screening of donors for artificial insemination is recommended, and guidelines are proposed. These consider the kinds of disorder in the presumptive donor, or his relatives, that would preclude his use as a donor, and the steps to be taken with respect to genetic counseling if a defective baby is born following the procedure.
Prenatal fetoscopic diagnosis of the Apert syndrome
Authors: Leonard Claire O. , Daikoku Norman H. , Winn Kevin , Opitz John M.
Published: June 2005

We report the prenatal diagnosis of the Apert syndrome by fetoscopy. The patient was a 22‐year‐old college student with this autosomal dominant form of acrocephalosyndactyly whose first pregnancy had resulted in a stillborn, affected infant. Fetoscopy at 17 weeks showed that she was carrying another affected fetus, and the pregnancy was terminated.
Genetic aspects of Huntington's chorea: Results of a national survey
Authors: Hayden M. R. , Beighton P.
Published: June 2005

In a nationwide survey of South Africa we ascertained and investigated 157 persons with Huntington's chorea and collected data on a further 328 deceased individuals who had probably been affected. Of the 157 respondents, 17 had a juvenile onset and in 13 of these the father had been the affected parent. Further analysis of these data shows that the father had transmitted the gene to 5 of the 6 children with onset in the first decade. The heterozygote frequency in the combined white population and the group of mixed ancestry is 6.7 × 10−5 and the minimum number of heterozygotes is 458 in South Africa (1 in 13,000). The disorder is extremely rare in African Negroes; only 3 affected individuals were identified out of a population of 19 million.
Phenotypic effects of inherited balanced translocation
Authors: Ying Zhao , Zaiyu Cheng , Chunyun Liu , Lo Wilson Hwei‐yuen , Opitz John M. , Opitz John M.
Published: June 2005

We report two cases of inherited balanced translocation with severe CNS abnormalities and a number of other physical findings. In both cases a multiple congenital anomalies/mental retardation (MCA/MR) syndrome was supected However, in one case, parturitional and neonatal complications probably resulted in brain damage; in the other, prenatal brain damage due to intoxication from a dead twin or porencephalic cysts due to vascular accidents remain unconfirmed hypotheses. It is concluded that no MCA/MR syndrome was present and that the inherited balanced translocation was a coincidental finding in these two braindamaged, mentally retarded children.
The distal arthrogryposes: Delineation of new entities – review and nosologic discussion
Authors: Hall J. G. , Reed S. D. , Greene G.
Published: June 2005

We report on 44 patients (18 with additional affected family members), with con genital distal limb contractures identified from a large study of over 350 patients with congenital joint contractures. Fourteen propositi (seven familial cases, seven isolated cases) had a newly recognized form of arthrogryposis, which we have designated distal arthrogryposis type I, with the predominant manifestations of autosomal dominant inheritance; tightly clenched fists at birth, with medially overlapping fingers, ulnar deviation, and camptodactyly in adults; and positional foot deformities. Contractures at other major joints are variable. There are no associated visceral anomalies; intelligence is normal. There can be marked intrafamilial and interfamilial variability. Twenty‐two propositi with similar distal contractures had additional findings and were classified into five subcategories of distal arthrogryposis (type IIA‐E). Among type II patients cleft palate, cleft lip, small tongue, trismus, ptosis, epicanthal folds, keratoconus, short stature, scoliosis, a unique hand position, and dull normal intelligence were seen. These characteristics were seen in various combinations and patterns and allowed sorting into groups that were the basis for the categorization. The remaining eight propositi were recognized to have previously described conditions with distal contractures and autosomal dominant inheritance, ie, the Freeman‐Sheldon syndrome, trismus‐pseudocamptodactyly syndrome, congenital contractual arachnodactyly, and familial camptodactyly.

Pathogenetically we postulate similar underlying defects of abnormal tendon attachments, attenuation, and absence; careful nosologic comparisons are important for prognostic counseling and habilitative management.
The genetics of malignant hyperthermia: Evidence for heterogeneity
Authors: McPherson Elspeth , Taylor Claude A. , Opitz John M.
Published: June 2005

Study of phenotype and familial distribution of malignant hyperthermia (MH) suggests heterogeneity with MH possibly being a symptom of several disorders. Review of all reported family studies supports the concept of heterogeneity with autosomal dominant inheritance in about one‐half of the families. There is no strong evidence for other mendelian patterns of inheritance, but sporadic and possibly multifactorially determined cases are common. MH is also seen in other musculoskeletal disorders. We report 12 Wisconsin families with MH and outline a preliminary approach to the counseling of MH patients and their families.
Phenylalanine levels in PKU following minor surgery
Authors: Fiedler Albert E. , Miller Martha J. , Bickel Horst , Cederbaum Stephen D.
Published: June 2005

Serum phenylalanine values were measured in 10 PKU patients who had minor operations. No individual value exceeded 17 mg/dl and the interpolated mean did not exceed 10 mg/dl on any postoperative day. These data confirm the consensus that minor surgery does not cause major and long‐lived perturbations of serum phenylalanine levels in PKU and requires no special dietary measures.
The Angelman (“Happy Puppet”) syndrome
Authors: Williams Charles A. , Frias Jaime L. , Opitz John M.
Published: June 2005

We report studies of six patients with the Angelman “Happy Puppet” sydrome and compare the data with those from previous reports. The results confirm the classic findings of severe mental retardation, “puppet‐like” gait, characteristic craniofacial abnormalities, and frequent episodes of laughter and suggest that this syndrome is more common than previously thought. Computerized axial tomographs of the brain demonstrating unilateral cerebellar atrophy in one patient constitute the first direct evidence of cerebellar abnormalities in this syndrome.
Genetic aspects of retinitis pigmentosa in China
Authors: Hu Dan‐Ning
Published: June 2005

We analyzed 151 pedigrees (209 cases) of retinitis pigmentosa in Shanghai, China. Of the 209 cases, the proportion of autosomal recessive (AR), autosomal dominant (AD), X‐linked recessive (XR), and simplex cases is 33.1, 11, 7.7, and 48.3% respectively. The average age of onset was 24.7 years in the AD type, 22.9 years in the AR and five years in the XR type. The average refractive errors were −1.88 D in the AD type, −2.37 D in the AR type, and −5.72 D in the XR type. In addition, 24, 100 persons were screened and six cases of retinitis pigmentosa were found. The gene frequencies of the AR (including simplex cases), AD, and XR types as calculated from the disease prevalence were 0.0142267, 0.0000137, and 0.0000384, respectively. The gene frequency of the AR type as calculated from the frequency of consanguinity (15.9%) was 0.00389, which is much less than that calculated from the prevalence. The probable explanation is that the AR type of retinitis pigmentosa really consists of several different disease entities, with each entity representing a separate gene mutation. The number of different mutations within the AR group is estimated to lie between 11 and 41.
Tetrasomy 21 in an infant with down syndrome and congenital leukemia
Authors: Jabs Ethylin Wang , Stamberg Judith , Leonard Claire O. , Opitz John M.
Published: June 2005

A prematurely born infant with the manifestations of Down syndrome and congenital monocytic leukemia was found, by Q and R banding, to have the karyotype 48,XY, +21, +21. This appears to be the first case of tetrasomy 21 documented by banding.

Clinically, the infant was indistinguishable from trisomic Down syndrome patients. He died at 4 days of respiratory insufficiency owing to hyaline membrane disease and E coli septicemia.
Partial trisomy 15 in a male with severe psychomotor retardation (48,XY,+15q−, +mar(15))
Authors: Voss Ruth , Lerer I. , Maftzir G. , Sheinis M. , Cohen M. M.
Published: June 2005

An abnormal karyotype consisting of 48 chromosomes has been found in a 16‐year‐old boy with severe psychomotor retardation and congenital anomalies. The two extra chromosomes: a 15q− and a small metacentric marker appear as derivatives of chromosome 15 (48,XY, +15q−, +mar(15). The healthy father has a mosaic chromosome constitution 46,XY/47,XY, +mar(15) and this additional chromosome is also present in the propositus. It is suggested that the presence of the extra chromosome in the father's germ cells may play a role in the production of the additional 15q− chromosome responsible for the clinical syndrome of the propositus.
Assessment of clinical variables and counseling needs in patients with retinitis pigmentosa
Authors: Boughman Joann A. , Caldwell Robin J. , Opitz John M.
Published: June 2005

Many medical and personal factors must be considered when attempting to provide comprehensive genetic counseling to families with retinitis pigmentosa (RP). Adequate diagnostic evaluation, the initial step in the counseling process, is not always readily obtained. Prognosis is difficult to assess, and genetic type may be impossible to establish in certain pedigrees. A nationwide questionnaire survey of 899 probands with RP and allied disorders was conducted, and generated data on the patient's perceptions of the clinical aspects of the disease, family history, and the understanding of the disorder by affected persons and their relatives.

This study emphasizes the clinical variability of RP and summarizes differences in age of onset of the different genetic types. Clearly, patients must be evaluated extensively and carefully to diagnose retinitis pigmentosa accurately. The extent and limitations of the diagnostic evaluation should be clearly understood by the counselor because some patients with sporadic phenocopies may be diagnosed as having retinitis pigmentosa. Counseling about prognosis should include information regarding the great variation among and within inheritance groups, families, and individuals with respect to age of onset and natural history of the disorder. All patients should be considered for hearing evaluations since as many as 30% of RP patients may have hearing impairments. Because no treatment is currently available for most RP patients, genetic counseling and supportive follow‐up should be viewed as an essential service for this common group of genetic disorders, and cooperation with the ophthalmologic diagnostician should be actively sought.