bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of chorion type on normal and abnormal developmental variation in monozygous twins
Authors: Melnick Michael , Myrianthopoulos Ntinos C.
Published: June 2005

To determine the effects, if any, of chorion type on normal and abnormal developmental variation in monozygous (MZ) twins, we tested the hypothesis that disparate environments that are related to chorion type have no effect on this variation. The parameters studied included congenital anomalies and dermatoglyphics (total ridge count and right‐left asymmetry). With the exception of total ridge count, analyses of these data failed to reject the null hypothesis. Dichorionic MZ twins had a significantly greater within‐pair variation than monochorionic MZ twins for total ridge count. In summary, then, these data could offer little support to prior speculation that monochorial placentas may present less favorable environments for fetal development.
Brachydactyly C, short stature, and hip dysplasia
Authors: Fitch Naomi , Jequier Sigrid , Costom Bruce
Published: June 2005

Short stature may be a component of the brachydactyly C syndrome. A family is presented in which the propositus has brachydactyly C, short stature, and hip dysplasia.
Deletion mapping: Further evidence for the location of acid phosphatase (ACP1) within 2p23
Authors: Emanuel B. S. , Zackai E. H. , Van Dyke D. C. , Swallow D. M. , Allen F. H. , Mellman W. J.
Published: June 2005

The human red cell acid phosphatase (ACP1) locus was assigned to region 2p23→2pter by Ferguson‐Smith et al [3], more specifically to 2p23 by Hamerton et al [5]. We describe two unrelated patients with deletion of chromosome 2, with similar breakpoints in the distal portion of band p23 (del(2) (p23)). ACP1 typing in both patients revealed heterozygous BA phenotypes. Thus, we assign the locus for ACP1 to the distal portion of 2p23.
Neuraminidase in Cultured Fibroblasts and Leucocytes of Homozygotes and Heterozygotes for the Mucolipidosis II Gene (I‐Cell Disease)
Authors: Potier M. , Melancon S. B. , Dallaire L. , Chicoine R. , Mameli L. , Bélisle M.
Published: June 2005

The significance of neuraminidase deficiency reported to be the primary defect in mucolipidosis II has been evaluated by determination of this enzyme activity in cultured fibroblasts, culture medium, and leucocytes from homozygote and heterozygous carriers of the disease. A new and sensitive fluorometric assay of neuraminidase was used with sodium (4‐methylumbelliferyl‐α‐D‐N‐acetylneuraminate) as substrate. We report: 1) nearly total deficiency of neuraminidase in mucolipidosis fibroblasts, 2) partial deficiency of this enzyme in leucocytes of one patient, 3) this decreased activity ceases to exist following Triton X‐100 treatment, and 4) intermediary mean neuraminidase activity in fibroblasts and leucocytes from obligate heterozygotes. Although these results would be consistent with the suggestion that neuraminidase deficiency is the primary defect in this disease, evidence from the work of other authors suggests that the enzyme deficiency results from a secondary effect of the mucolipidosis II mutation.
The questionnaire to parents of children with the Down syndrome: How to inform the parents and psychological responses to counseling
Authors: Shiono Hiroshi , Kadowaki Jun‐Ichi
Published: June 2005

This study determined the experience of 137 sets of parents when they were informed that their child had Down syndrome and how they would have preferred this matter to have been handled. The survey revealed that the majority of parents would have preferred being told as soon as possible, with both of them present, and that they had suspected something wrong at the birth of the child.

This information prompted us to analyze critically the parental experiences and to formulate a positive approach, with sensitive, supportive, and progressive counseling.
The perrault syndrome: Autosomal recessive ovarian dysgenesis with facultative, non‐sex‐limited sensorineural deafness
Authors: Pallister Philip D.
Published: June 2005

We report three sisters with ovarian dysgenesis; all three and two of their otherwise apparently normal brothers also had moderate to severe sensorineural deafness. Three similarly affected sibships are known, and the total of 14 affected patients includes three males with deafness without gonadal defect, one woman with ovarian dysgenesis without deafness, and ten women with ovarian dysgenesis and deafness. In two families parental consanguinity is known. We conclude that this condition, which we propose to designate the Perrault syndrome, is an uncommon autosomal recessive trait with obligatory ovarian dysgenesis in female homozygotes and facultative deafness in male and female homozygotes. Right bundle branch block and mental retardation may possibly be additional, less common pleiotropic manifestations.
Genetics of acheiropodia (“The handless and footless families of Brazil”): XI. Pathologic aspects
Authors: Marçallo F. A. , Pilotto R. F. , Freire‐Maia A.
Published: June 2005

We report another case of acheiropodia, a rare autosomal recessive trait of distal limb deficiency, to date seen only in Brazil in persons of Portuguese ancestry. The patient's parents were first cousins; she had two younger affected sisters. She presented with signs of vascular insufficiency of the lower stumps, which after amputation were found to lack large vessels below the knee.
In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda
Authors: Delvin Edgard E. , Glorieux Francis H. , Lopez Elida
Published: June 2005

Sulfate (35SO4−2) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta “congenita,” six patients with osteogenesis imperfecta “tarda,” three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminoglycans in mutants as seen by the chase experiments was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of 35SO4−2 incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.
Anatomical studies of a boy trisomic for the distal portion of 13q
Authors: Pettersen James C.
Published: June 2005

A boy trisomic for the distal portion of 13q was dissected in detail and compared to 8 cases of complete trisomy 13 previously studied in our laboratory. The comparison shows that the partial trisomy 13q case did not correspond well to a muscle phenotype based on 6 variations common in trisomy 13, but rather to a larger muscle phenotype that included variations less frequently observed in complete trisomy 13. Additional cases of partial trisomy 13 must be studied before these findings can be related to specific portions of chromosome 13.
Complete androgen insensitivity with a normal amount of 5α‐dihydrotestosterone‐binding activity in labium majus skin fibroblasts
Authors: Kaufman Morris , Pinsky Leonard , Baird Patricia A. , McGillivray Barbara C.
Published: June 2005

We have studied labium majus skin fibroblast strains from six unrelated, previously unreported, patients with complete androgen insensitivity (CAI). Four have markedly reduced specific 5α‐dihydrotestosterone‐binding (DHT‐binding) activity (receptor‐negative). The other two (receptor‐positive) have normal activities in whole‐cell homogenates, the 100,000g supernatant of cell sonicates prepared in 0.4 M KCl, purified whole nuclei, and the nuclear fraction that resists extraction with 0.4 M KCl. In one of the two, the DHT‐binding macromolecules in the cytosol and 0.4 M KCl‐extractable nuclear fraction have normal molecular sieving profiles and binding activities. One of the receptor‐positive patients has maternally related affected relatives in three successive generations. Appreciable unexplained interexperimental variation of the DHT‐binding activities in genital skin fibroblast strains demands that multiple assays be performed on a strain before its receptor status is classified quantitatively. In our experience to date with genital skin fibroblasts, four of 13 propositi with CAI have been receptor‐positive.
Autosomal recessive craniometaphyseal dysplasia
Authors: Penchaszadeh Victor B. , Gutierrez Estatio R. , Figueroa P. Ernesto
Published: June 2005

The autosomal recessive form of craniometaphyseal dysplasia was ascertained in two sibships with two affected individuals each. All four parents were normal and in one case they were consanguineous; both families were living in Caracas but had their origins in Tenerife Island (Canary Islands), although no genealogic link between them could be established. The age of the patients ranged from 6 to 14 years and the main clinical alterations were a thick bony wedge over the bridge of the nose, dystopia canthorum, ocular hypertelorism, enlarged malar prominences and mandible, wide alveolar ridges, dental abnormalities, and genu valgum; narrowing of the nasal passages led to mouth breathing. A slight, mixed hypoacusia was present in two patients; no other signs of cranial nerve involvement were detected. The cardinal radiographic features were hyperostosis and sclerosis of the calvarium, the base of the skull, and the facial bones and mandible; increased bone deposition on the walls of the paranasal sinuses; under‐pneumatization of mastoid cells; cortical hyperostosis of the diaphyses of the short and long tubular bones, and gradual, club‐shaped widening of the metaphyses, which had thin cortex and undermineralized medullary bone. The clinical and radiologic alterations had an increasing gradient of severity with age. The phenotype of recessive craniometaphyseal dysplasia is not clearly differentiated from the dominant form but easily so from two other recessive conditions with which it was formerly confused: Pyle disease and craniodiaphyseal dysplasia.
Frontometaphyseal dysplasia—evidence for X‐linked inheritance
Authors: Gorlin Robert J. , Winter Robert B.
Published: June 2005

Fewer than two dozen cases of frontometaphyseal dysplasia have been reported, some doubly or erroneously. In most reports, no information is available on possible variable manifestations in female relatives. Statements that the disorder is inherited as a dominant trait, and as an X‐linked recessive have caused us to consider genetic heterogeneity. A recent large kindred prompted us to survey all published examples. We asked authors to reexamine the families they studied for any expression in relatives. In some cases, no further information could be elicited, but some additional information was gathered and pedigrees modified. This evidence was sufficient to indicate X‐linked inheritance, with severe manifestations in males and extremely variable manifestations in females.
Malformation syndrome associated with small extra chromosome
Authors: Carmi Rivka , Abeliovich Dvorah , Bar‐Ziv Jacob , Karplus Michael , Cohen Maimon M. , Opitz John M.
Published: June 2005

We report an infant with a previously apparently unreported lethal malformation syndrome concentrated primarily on the left half of the body, but including midline defects such as meningomyelocele, cleft lip and cleft palate, and imperforate anus. The infant also had a small extra metacentric chromosome in 60% of lymphocytes. It is postulated that the small extra chromosome (whose origin remains unknown) caused the infant's condition, and that its asymmetry is compatible with an uneven distribution of the normal and aneuploid cell lines in the two halves of the body during critical phases of prenatal development.
Genetic counseling for adoptees at risk for specific inherited disorders
Authors: Omenn Gilbert S. , Hall Judith G. , Hansen Kenneth D.
Published: June 2005

We present 5 cases in which family history showed that a child given up for adoption some years earlier was at 50% risk for inheritance of Huntington disease, myotonic dystrophy, Fabry disease, von Willebrand disease, and Waardenburg syndrome, respectively. In all cases, the biological mothers (the probands) requested that the genetic counseling provided for them and their children be shared with the adoptive family. The decision whether or not to seek out the adoptee was based upon explicit assessment of the potential benefits and potential difficulties involved in contacting the adoptive family and attempting to provide genetic counseling. We have formulated some recommendations for dealing with other families with similar separation of relatives by adoption on the basis of these experiences.
Beta‐galactosidase deficiency: Studies of two patients with prolonged survival
Authors: Taylor Harold A. , Stevenson Roger E. , Parks Stephen E. , Kelly T. E.
Published: June 2005

Two adults with β‐galactosidase deficiency were studied. Differences in a number of β‐galactosidase parameters (pH optima, heat denaturation, NaCl kinetics) were noted between the patients. Differences were also noted in β‐galactosidase electrophoretic mobilities and urinary oligosaccharides; however, there was no complementation in cell fusion studies. It is suggested that these two patients have different primary mutations at the β‐galactosidase locus which are probably structural in nature.
Femoral hypoplasia—unusual facies syndrome
Authors: Hurst Daniel , Johnson Donald F.
Published: June 2005

A patient with femoral hypoplasia – unusual facies syndrome is presented; this is the eleventh reported patient with this syndrome. In reviewing the literature, three other patients were discovered to have the syndrome.
Congenital macular colobomas and short‐limb skeletal dysplasia
Authors: Smith Richard D. , Fineman Robert M. , Sillence David O. , Lester Patric D. , Nixon G. William , Rimoin David L. , Lachman Ralph S. , Opitz John M.
Published: June 2005

We report a previously undescribed association of severe short‐limbed dwarfism and macular colobomas with histological changes of cartilage resembling to some extent those of diastrophic dysplasia.

Chance occurrence of two rare disorders due to different causes is considered unlikely and the patient is presumed to have a syndrome of, as yet, unknown cause.
Possible X‐linked anencephaly and spina bifida—report of a kindred
Authors: Toriello Helga V. , Warren Stephen T. , Lindstrom Janice A. , Opitz John M.
Published: June 2005

Causal heterogeneity of anencephaly and spina bifida has been demonstrated; in rare families the neural tube defect may be caused by a single gene. We report a family in which four cases of anencephaly or spina bifida may represent X‐linked inheritance.
A new genetic concept: Uniparental disomy and its potential effect, isodisomy
Authors: Engel Eric
Published: June 2005

In recent years, cytogenetic studies of spontaneous abortion products have disclosed a relatively high frequency of aneuploid embryos. These karyotypic anomalies chiefly stem from meiotic errors affecting the distribution of the chromosomes in one of the two gametes. This information not only implies the remarkable frequency of gonocyte aneuploidy but also reveals the prevalence of certain types of errors. It follows that gametal haploidy is often altered by the loss (nullisomy) or the addition (disomy) of certain members, in particular the X, the Y, and chromosomes 15, 16, 21, and 22.

Therefore, it is to be expected that, in some exceptional zygotes, euploidy could result from the random union of a disomic gamete with a gamete nullisomic for the homologue. To this hypothetical phenomenon ‐ which is, however, statistically likely and foreseeable ‐ we have ascribed the name of uniparental disomy, owing to the fact that both members of such a pair arise from only one parent. Furthermore, such a mechanism implies the probability of introducing into the genome pairs of chromosomes with whole sequences of identical alleles, a consequence which we describe by the neologism of isodisomy. Such homozygosity for a series of colinear alleles implies, from the genetic stand‐point, risks and advantages akin to those of parental consanguinity.

An analogous mechanism could also modulate and modify the consequences of trisomies in which entire segments of two of the three implicated chromosomes, including the supernumerary one, could as well be isoallelic (isodisomic trisomy or di‐isotrisomy). This article briefly states some other predictions stemming from the concept of uniparental disomy, whose confirmation should serve as a test of the proposed hypothesis.
The importance of A′‐d ridge count in dermatoglyphic diagnosis of the Ullrich‐Turner syndrome
Authors: Otto P. A. , Otto Priscila Guimarães , Opitz John M.
Published: June 2005

The dermatoglyphic characteristics of 52 women with the Ullrich‐Turner syndrome were studied and compared to those of a control group of 50 normal women. Through the use of discriminant analysis, it is shown that the use of the A'‐d ridge count alone has the same efficiency in separating Ullrich‐Turner syndrome patients from normal female subjects as discriminant functions here derived and other methods already published in the literature.
Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly—a new syndrome? Part II: Neuropathological considerations
Authors: Clarren Sterling K. , Alvord Ellsworth C. , Hall Judith G. , Optiz John M.
Published: June 2005

Unusual and virtually identical hypothalamic tumors were recently studied in three unrelated neonates with a similar complex malformation syndrome. Previous reports of either the hypothalamic tumors or the syndrome as a whole have not been found. Each tumor was apparent on the inferior surface of the cerebrum and extended from the optic chiasma to the interpeduncular fossa. The tumor replaced the hypothalamus and other nuclei which originate in the embryonic hypothalamic plate; it was principally composed of cells resembling primitive, undifferentiated germinal cells. The term “hamartoblastoma” is used to designate these tumors in order to emphasize the malformational and neoplastic aspects. In addition, short olfactory tracts suggest a relation to the arrhinencephaly field defect.
GENFILES: A computerized medical genetics information network. II. MEDGEN: The clinical genetics system
Authors: Mitchell Joyce A. , Loughman William D. , Epstein Charles J.
Published: June 2005

MEDGEN, a clinical genetics information storage and retrieval system, facilitates the handling of medical records for the central genetics clinic and satellite clinics conducted by the University of California, San Francisco. The system is part of the GENFILES genetics network, which handles all of the genetics data generated by a comprehensive medical genetics center.

The clinical data stored on each patient include 1) diagnoses, which utilize McKusick catalog numbers as well as our own diagnostic codes; 2) relevant medical, gestational, and pregnancy history; 3) clinical manifestations (functional and structural); 4) karyotype information through a crosslink to the cytogenetics file; 5) ethnic origin of the patients; 6) physical status and sex of the patient; 7) laboratory studies, including results of metabolic tests; and 8) any additional remarks deemed necessary for complete understanding. The date, staff member attending, and physical location of each visit also are recorded.
Virilism as a late manifestation in the Bardet‐Biedl syndrome
Authors: Haning Ray V. , Carlson Ian H. , Gilbert Enid F. , Shapiro Sander S. , Opitz John M. , Karp Laurence E.
Published: June 2005

The second case of virilism as a late manifestation of Bardet‐Biedl syndrome (BBS) is described, with endocrine and histological evaluation. Both cases manifested ovulatory cycles and developed virilism in adulthood. Elevated plasma testosterone and 17‐OH‐progesterone were not suppressed by dexamethasone but were suppressed by medroxyprogesterone acetate. Peripheral and ovarian venous blood obtained at the time of surgery demonstrated a marked gradient for testosterone in both ovaries and for progesterone in the ovary bearing the corpus luteum. Histological evaluation of the ovaries demonstrated bilateral ovarian stromal hyperplasia with focal hyperthecosis. Bilateral ovariectomy resulted in complete correction of the endocrine abnormality, although the established hirsutism remains a mark of previous androgen excess.
Autosomal recessive microcephaly and micromelia in Cree Indians
Authors: Ives Elizabeth J. , Houston C. Stuart , Optiz John M.
Published: June 2005

In a highly consanguineous, predominantly Cree Indian community in northern Saskatchewan, Canada, 14 similarly malformed babies have been born to eight different mothers since 1953. Six of these infants are reported to assist delineation of the syndrome.

The major manifestations of the condition are: Intrauterine growth retardation, perinatal death, marked microcephaly, and severe malformations of the limbs, especially the arms. Elbows are fused, forearms are greatly shortened and usually contain only a single bone, and the hands are very abnormal with only two to four malformed digits.

Parental consanguinity, a sex ratio close to one, and a 25% segregation ratio all support autosomal recessive inheritance of this syndrome.
X‐linked mental retardation: Renpenning revisited
Authors: Fox Patricia , Fox Dale , Gerrard John W. , Optiz John M.
Published: June 2005

Nine men with X‐linked mental retardation (MR) belonging to the family originally described by Renpenning and his colleagues have been reexamined and restudied. None of these men have the fragile X chromosome, and none have macro‐orchidism; their testes range in size from small to average. All but one are severely retarded; one has an IQ of 70, the mean IQ of the remainder is 30 with a range of 18 to 45. They are short in stature, have small or normal‐size ears and lower jaws, and a moderate degree of microcephaly, the mean skull circumference being just below two standard deviations from the normal.
Lower limb anomalies in the thrombocytopenia absent‐radius (TAR) syndrome
Authors: Ray Robin , Zorn Elinor , Kelly Thaddeus , Hall Judith G. , Sommer Annemarie , Holmes Louis B.
Published: June 2005

We report a case of the TAR syndrome with severe abnormalities of the lower limbs. The syndrome of thrombocytopenia and radial deformities occasionally presents diagnostic difficulties when severe limb anomalies are present. Based on this case and 2 additional cases from the literature, reduction anomalies of the lower limbs should be considered part of the TAR syndrome.
The genetic dynamics of disease
Authors: Murphy Edmond A. , Opitz John M.
Published: June 2005

The notional principles of the genetics of disease are broadly discussed. Disease is an intrinsically vague term that represents the incongruity between the inner milieu of the organism and the environment. Its dynamics, then, cannot be reduced to naive statements about selection which may operate, and operate conflictingly, on several different levels of organization. Evolutionary selection results from the advantage of complexity, and the fundamental theorem of genetic dynamics — that mutational debts must eventually be paid in full — may be false or, at best, approximate. The traditional models (mendelian, galtonian, and threshold) are set in a context that identifies certain features of disease that hitherto have been totally ignored. Neither invention nor traditional analysis has been adequate. Models should be made individually adequate for the study of diseases; the diseases should not be trimmed to fit the models.
Familial cushing disease
Authors: Salti Ibrahim S. , Mufarrij Imad S. , Opitz John M.
Published: June 2005

A 28‐year‐old woman and her niece presented with manifestations of the Cushing syndrome. Endocrine studies, including small‐ and large‐dose dexamethasone‐suppression tests confirmed the diagnosis of pituitary ACTH excess. The first patient had a sella of normal size and went into clinical and hormonal remission after external pituitary irradiation, and she has remained well on follow‐up for 9 years. The niece had an enlarged sella turcica on tomography and is receiving a course of external pituitary irradiation.
Prenatal diagnosis of exstrophy of the cloaca
Authors: Gosden Christine , Brock D. J. H. , Opitz John M.
Published: June 2005

While screening for neural tube defects, three cases of exstrophy of the cloaca were found through elevated second‐trimester maternal serum alphafetoprotein levels. Measurement of amniotic fluid alphafetoprotein and examination of the structure of rapidly adhering cells confirmed the abnormalities, and the pregnancies were terminated. Subsequent studies of cholinesterase isozymes by acrylamide electrophoresis showed an abnormal acetylcholinesterase band in each of the three amniotic fluids. During the same period, two more cases of exstrophy of the cloaca were identified in spontaneous abortions and another one in a stillbirth. It is suggested that the condition is more common than has been previously suspected and is often misclassified as omphalocele.
Prenatal diagnosis of Maroteaux‐Lamy syndrome
Authors: Dyke Daniel L. Van , Fluharty Arvan L. , Schafer Irwin A. , Shapiro Larry J. , Kihara Hayato , Weiss Lester , Opitz John M.
Published: June 2005

Maroteaux‐Lamy syndrome exhibits deficient activity of the enzyme arylsulfatase‐B in cultured skin fibroblasts. Prenatal diagnosis was successfully attempted in two pregnancies of a consanguineous Chaldean couple whose first child is affected with Maroteaux‐Lamy syndrome. In both instances, deficient arylsulfatase‐B activity was observed in amniotic fluid cell cultures, and the diagnosis was confirmed by 35S‐sulfate studies and postmortem enzymology and electron microscopy. The prenatal diagnosis of Maroteaux‐Lamy syndrome remains problematic. Residual activity of arylsulfatase‐B in the affected homozygote can make interpretation difficult, and the behavior of many lysosomal enzymes varies greatly in response to tissue culture conditions and enzyme extraction processes.
Psychotherapeutic considerations in genetic counseling
Authors: Targum Steven D. , Opitz John M.
Published: June 2005

It is essential to consider the psychodynamic aspects of genetic counseling to attain the best outcome for the family. Narcissistic injury (reduced selfesteem), excessive defensiveness, and depressive reactions may impede an effective resolution of feelings and preclude the necessary adaptation to genetic diseases and the new realitities that have developed. Most parents of genetically affected children are capable of dealing with these conflicts. However, some individuals need help during the adaptation process by assisting them to grive for their disappointments and to help them develop new goals for themselves and for the baby that was born.

This paper describes psychodynamic concepts that might be explored to facilitate conflict‐resolution resulting from the occurrence of genetic disease.
The centralized prenatal genetics screening program of New York City: II. Establishment of prenatal diagnosis laboratory
Authors: Hsu Lillian Y. F. , Benn Peter A. , Karp Lawrence E.
Published: June 2005

Prenatal diagnosis of genetic disorders is now being made available to an increasing number of New York City women through the establishment of a large centralized laboratory. This laboratory contracts to provide genetic diagnostic services to municipal and private hospitals throughout the New York City area. It is the first project of such magnitude in the United States. Prior to the receipt of samples for diagnostic purposes, the laboratory was required to meet the highest technical standards, as established by a Cytogenetics Advisory Committee. A set of guidelines was drawn up detailing the procedure and protocols for all the analyses and the reporting of results, including a timetable according to which results were to be obtained. The Cytogenetics Advisory Committee continues to review cases on a regular schedule. One of the unique aspects of the laboratory has been the development of back‐up agreements with other area laboratories to assist in dealing with any problem that might disrupt the routine diagnostic service. The first year of operation of the laboratory has shown that financial, legal, and physical problems associated with designing and instituting a megacenter can be overcome. Similar programs should be encouraged.
Osteomesopyknosis: An autosomal dominant osteosclerosis
Authors: Stoll Claude G. , Collin Dominique , Dreyfus Jean , Opitz John M.
Published: June 2005

Radiographs of a 27‐year‐old sterile woman showed increased bone density. The lesions were localized to the spine and pelvis. The condition is inherited as an autosomal dominant trait and has been designated osteomesopyknosis.
A goodness‐of‐fit test for the polygenic threshold model: Application to multiple sclerosis
Authors: Sadovnick Adele D. , Spence M. Anne , Tideman Susan
Published: June 2005

Recently it has been suggested that multiple sclerosis may be a multifactorial disorder. We found in British Columbia 364 families (sibship size ⩾ 2) in which at least one sibling was diagnosed as having “clinically definite” multiple sclerosis. The data were tested for goodness‐of‐fit to the multifactorial model using an analysis that considers various parameters including ascertainment probability, heritability, and sex‐dependent prevalence rates. The results suggest that multiple sclerosis does not fit the multifactorial model. As an alternative genetic model we propose that a major gene could be responsible for at least a portion of the cases of multiple sclerosis.
Autosomal dominant cone‐rod dystrophy: A linkage study with 17 biochemical and serological markers
Authors: Ferrell Robert E. , Hittner Helen Mintz , Chakravarti Aravinda , Opitz John M.
Published: June 2005

Five generations of a family with autosomal‐dominant cone‐rod dystrophy (CRD) with complete penetrance have been previously studied extensively clinically. The young members of this family were reevaluated, and blood from 73 available family members was studied with 17 biochemical and serological markers. A total of 25 relatives was found to be affected. Linkage between the gene for CRD in this family and the markers studied could not be established by maximum likelihood analysis.
Duchenne muscular dystrophy carrier detection using logistic discrimination: Serum creatine kinase and hemopexin in combination
Authors: Percy Maire E. , Andrews David F. , Thompson Margaret W. , Opitz John M.
Published: June 2005

Creatine kinase (CK) activity and hemopexin concentration were measured in 208 serum samples from 104 normal females and 22 obligate carriers of Duchenne muscular dystrophy (DMD) 20–40 years old. Logistic discrimination was used to assess the effectiveness of the parameters alone or in combination in identifying DMD carriers. In this approach, a serum sample with particular CK, hemopexin, or a combination of CK and hemopexin values is given a probability that if drawn at random from a defined mixture of controls and carriers, it comes from a carrier. The carrier probability based on the biochemical tests can be directly combined with the carrier probability determined from a woman's pedigree to yield a final posterior probability that she is a carrier.

When CK and hemopexin were considered individually, 65 and 27% of the carriers, respectively, could be distinguished from 95% of the controls. When the two tests were used in combination, 82% of the carriers could be distinguished from 95% of the controls. When the two‐test method was applied to 93 possible carriers, 35 women were classified as carriers, whereas only 29 were identified using CK alone. This method can be extended to include other variables in order to further improve the identification of DMD carriers. It can also be applied to carrier detection in other genetic disorders.
Historical note: The extraordinary handless and footless families of Brazil – 50 years of acheiropodia
Authors: Freire‐Maia Ademar , Opitz John M.
Published: June 2005

The history of acheiropodia is divided into 4 phases: discovery, exploration, modern studies, and contemporary knowledge. The discovery phase (1929–1930) is represented by the publication of the 1st family. For about 30 years, it remained the only family referred to in a number of textbooks of medicine, biology, and others. In the exploration phase (1956–1966), the first family was reanalyzed, other families were ascertained and analysed, and some radiologic aspects of the anomaly were published. The modern phase (1968–1972) is characterized by a large series of studies on the clinical aspects of acheiropodia, including laboratory and radiological examinations, psychological tests, status of vision, electrocardiograms, etc. In the contemporary phase (since 1974), genetic aspects prevailed, and studies were published on segregation analysis, selection pressure, genetic load, mutation rate, etc. Each one of these 4 phases is analyzed in detail.
Familial insertional translocation of a portion of 3q into 11q resulting in duplication and deletion of region 3q22.1→q24 in different offspring
Authors: Williamson Roger A. , Donlan Michael A. , Dolan Cynthia R. , Thuline Horace C. , Harrison Mary T. , Hall Judith G. , Opitz John M.
Published: June 2005

The use of elongated prophase and prometaphase chromosome preparations has allowed detection of an insertion of a small segment of 3q into 11q in a kindred with 4 balanced carriers and 8 unbalanced offspring. Those with partial 3q deletion have a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome with an appearance suggestive of the Schwartz‐Jampel syndrome.
The del(4) (q31) syndrome‐A recognizable disorder with atypical Robin malformation Sequence
Authors: Davis Jeffrey M. , Clarren Sterling K. , Salk Darrell J. , Opitz John M.
Published: June 2005

Deletions of the terminal region of the long arm of chromosome 4 have been reported previously in 6 patients. With the addition of our patient with 46,XX,del(4) (pter→q31:), it becomes clearer that this is a recognizable syndrome. None of the 7 patients has had prenatal growth deficiency, while postnatal growth deficiency has been variable. The syndrome is typified by a Robin malformation sequence without apparent catch‐up growth of the mandible, anomalous auricles, a short nasal septum with a depressed nasal bridge, absent 5th finger creases, clinodactyly, and displacement of the toes. Mental retardation has been found consistently.
Meiotic consequences of pericentric inversions of chromosome 13
Authors: Wenger S. L. , Steele M. W. , Opitz John M.
Published: June 2005

A case is presented demonstrating meiotic consequences of inheritance of a pericentric inversion, inv(13)(p13q21), and suggesting, together with other similar reports reviewed, that certain manifestations (highly arched palate, long philtrum, polydactyly, microphthalmia, and capillary hemangiomata) result from duplication of the distal 13q while others (cleft lip/palate, scalp defects, congenital heart disease) result from duplication of the proximal 13q.
Ring 14 chromosome: Association with seizures
Authors: Lippe Barbara M. , Sparkes Robert S. , Opitz John M.
Published: June 2005

A one‐year‐old male with seizures and developmental delay was found to have a ring 14 chromosome without a major band deletion. This brings the number of documented r(14) cases to seven. These patients have focal cerebral atrophy with seizures as their dominant manifestation, together with few minor facial anomalies. This combination suggests that abnormalities in the 14 chromosome may result in rather nonspecific central nervous system maldevelopment and dysfunction and raises the possibility that unexplained seizures with minor anomalies and mental retardation may warrant chromosome investigation.
Dermo‐distortive urticaria: An autosomal dominant dermatologic disorder
Authors: Epstein Paul A. , Kidd Kenneth K. , Opitz John M.
Published: June 2005

A new hereditary physical urticaria, dermo‐distortive urticaria (DDU), is described in a Christian Lebanese family. DDU is characterized by the appearance of pruritic, erythematous, edematous, cutaneous swelling confined to the stimulated area in response to stimuli that vibrate or stretch the skin in a repetitive manner. The lesions appear within several minutes after stimulation and disappear within an hour. Extensive stimulation causes not only local urticaria but also a systemic response of faintness, headache, and facial erythema. Other than these annoying reactions, no other morbidity is associated with this disorder. While this disorder is certainly uncommon and its manifestations are more annoying than life threatening, it may be an important example of a heritable defect of inflammation control mechanisms. Although the mediator for the urticaria and systemic response was not isolated, a likely candidate is histamine. Computer analysis of the phenotype of 219 relatives in 6 generations shows that DDU is transmitted as an autosomal dominant trait with high penetrance. DDU is clinically distinct from hereditary angioneurotic edema, pressure urticaria, and dermographia. It is similar to vibratory angioedema (VA), but sufficient evidence to prove that DDU and VA are identical is not available.
Dysgerminoma in a patient with the syndrome of gonadal dysgenesis with a 45,X karyotype
Authors: Lindsay Alan N. , Sills Irene N. , MacGillivray Margaret H. , Fisher John E. , Voorhess Mary L. , Opitz John M.
Published: June 2005

A 19‐year‐old woman with the Ullrich‐Turner syndrome presented with a mass filling her entire pelvis. The tumor was a dysgerminoma. Only one other patient with a 45,X chromosome constitution has been reported with this form of malignancy.
Cytogenetic studies of familial and sporadic Alzheimer disease
Authors: White Beverly J. , Crandall Clare , Goudsmit Jaap , Morrow Chuck H. , Alling David W. , Gajdusek D. Carleton , Tijio J ‐H. , Opitz John M.
Published: June 2005

We present cytogenetic findings in 7 familial and 5 sporadic Alzheimer disease (AD) patients and 34 unaffected relatives, spouses, and normal controls. Our study was prompted by reports of increased chromosome abnormalities in patients and family members at risk for AD. Coded peripheral blood chromosome preparations were evaluated for aneuploidy, aberration rates, and banding patterns. Statistical analyses of our results showed no increase in aneuploidy or aberrations in AD patients, their relatives, or normals. Chromosome loss or gain in aneuploid cells was not specific except in two individuals. These two older persons studied, one with AD and one unaffected, were observed to have increased sex chromosome aneuploidy. This finding was attributed to aging and was not considered to be an effect of AD.
Congenital androgen insensitivity due to a qualitatively abnormal androgen receptor
Authors: Pinsky Leonard , Kaufman Morris , Summitt Robert L. , Opitz John M.
Published: June 2005

Complete or incomplete androgen insensitivity (AI) not associated with deficient specific 5α‐dihydrotestosterone (DHT)‐receptor activity in cultured genital skin fibroblasts may result from a qualitative receptor abnormality or a postreceptor defect in target cell sensitivity to DHT. We have studied a sporadic patient with complete AI whose mean receptor capacity (Bmax) is 34 fmol/mg protein and a second with incomplete AI, multiple affected maternal relatives, and a mean Bmax of 40 (normal: 15 – 50). Each has normal 5α‐reductase activity. The following qualities of the receptor activity are normal in each: Equilibrium dissociation constant (Kd), elution profile on gel chromatography, nuclear translocation of the DHT‐receptor complex, and 0.4 M KCl extractability of the nuclear complex. When preincubated at 37°C and assayed at 42°C (compared with the usual 37°C) the receptor activity in cells of the “complete AI” patient decreased much more (60%) than that of any of 7 control cell lines (± 20%); the activity in cells of the “incomplete AI” patient, in contrast, decreased to a variable, questionably abnormal extent. When preincubated, assayed, and chased at 37°C with excess radioinert DHT, the androgen‐receptor complexes in both patients dissociated with a rate constant (k−1) about 18 × 10−3 min−1 compared with a normal of 5.9 ± 0.32 × 10−3 min−1 (± SEM; n = 15). We have thus defined novel qualitative defects of the androgen receptor activity in two patients who have different clinical degrees of congenital AI despite normal levels of androgen binding. These defects will be useful as markers for genetic studies and as molecular models for steroid‐resistant cancer in man.
Prometaphase chromosomes in five patients with the Brachmann‐de Lange syndrome
Authors: Breslau Elizabeth J. , Disteche Christine , Hall Judith G. , Thuline Horace , Cooper Pat , Opitz John M.
Published: June 2005

We analyzed the prometaphase chromosomes of 5 patients (including one pair of sibs) with the Brachmann‐de Lange syndrome (BDLS), and did not find a significant chromosome abnormality in any of them. It appears that two distinct entities can be distinguished on clinical and chromosomal bases: the BDLS and the dup(3q) syndrome. We still recommend chromosome studies in any patients with BDLS and BDLS‐like manifestations.
An autosomal recessive ectodermal dysplasia syndrome of hypotrichosis, onychodysplasia, hyperkeratosis, kyphoscoliosis, cataract, and other manifestations
Authors: Alves A. F. P. , dos Santos P. A. B. , Castelo‐Branco‐neto E. , Freire‐Maia N. , Opitz John M.
Published: June 2005

We describe a 20‐year‐old woman with generalized trichodysplasia, dry skin with scaling, hyperchromic spots on limbs, hyperkeratosis (particularly intense on soles), dermatoglyphic abnormalities, onychodysplasia, shortness of stature, kyphoscoliosis, unusual facial appearance, minor malformations of limbs, bilateral nuclear cataract, narrow palpebral fissures, entropion, trichiasis, etc. The condition is probably due to an autosomal recessive gene. The patient is the only affected member in a sibship of four whose parents are second cousins.
Some epidemiological aspects of pyloric stenosis in British Columbia
Authors: Walpole Ian R. , Opitz John M.
Published: June 2005

The records of an ongoing Health Surveillance Registry that utilizes multiple sources of ascertainment were used to study the incidence rate of infantile hypertrophic pyloric stenosis (IHPS) in liveborn children in British Columbia during the period 1966–1977 inclusive. The incidence was 4.6 males/1,000 livebirths and 1.2 females/1,000 livebirths, giving a male to female ratio of 3.1 to 1. No significant overall incidence variations with time could be shown during the study period. There was suggestive evidence of independent sex‐incidence variation in different geographical regions, which clearly warrants further investigation.
Symphalangism with multiple anomalies of the hands and feet: A new genetic trait
Authors: Learman Yaffa , Katznelson Mariassa Bat‐Miriam , Bonné‐Tamir BatSheva , Engel Joel , Hertz Marjorie , Goodman Richard M. , Opitz John M.
Published: June 2005

We report a new autosomal dominant condition involving hands and feet of an Arabic father and 5 of his 11 children. This trait is characterized by symphalangism, syndactyly, brachydactyly type D, clinodactyly, and hypoplasia of the thenar and hypothenar eminences. Affected persons had symphalangism and syndactyly plus some or all or part of the other anomalies. Symphalangism, the main defect in this syndrome, showed variable expressivity. A distinct dermatoglyphic pattern was observed in all affected relatives. Linkage studies were done; however, no linkage was demonstrated.
The bingo model of survivorship: 1. Probabilistic aspects
Authors: Murphy Edmond A. , Trojak Joseph E. , Hou William , Rohde C. A. , Opitz John M.
Published: June 2005

A “bingo” model is one in which the pattern of survival of a system is determined by whichever of several components, each with its own particular distribution for survival, fails first. The model is motivated by the study of lifespan in animals. A number of properties of such systems are discussed in general. They include the use of a special criterion of skewness that probably corresponds more closely than traditional measures to what the eye observes in casually inspecting data. This criterion is the ratio, r(h), of the probability density at a point an arbitrary distance, h, above the mode to that an equal distance below the mode. If this ratio is positive for all positive arguments, the distribution is considered positively asymmetrical and conversely.

Details of the bingo model are worked out for several types of base distributions: the rectangular, the triangular, the logistic, and by numerical methods, the normal, lognormal, and gamma.
Analysis of banding patterns in a case of ring chromosome 21
Authors: Richer Claude‐Lise , Fitch Naomi , Sitahal Sharon , Murer‐Orlando Manuela , Jean Pierre , Opitz John M.
Published: June 2005

An infant with psychomotor retardation, hypertonia, microphthalmia, buphthalmos, cleft palate, nail dysplasia, and hypospadias had the karyotype 46,XY, r(21)/45,XY,‐21. Cytogenetic analysis of prophase and prometaphase chromosomes showed the breakpoints of chromosome 21 were at p12 and q22.2.
Malformation syndrome of duplication 12q24.1→qter
Authors: Melnyk Andrew R. , Weiss Lester , Van Dyke Daniel L. , Jarvi Paul , Opitz John M.
Published: June 2005

While duplication and deletion of the short arm of chromosome 12 cause well‐recognized syndromes, duplication of the long arm of chromosome 12 is rarely observed. We are reporting a duplication of chromosome 12 distal to band q24.1 in a five‐month‐old child. His chromosome constitution is 46,XY,‐4, + der(4),t(4:12)(p16;q24.1)mat. The balanced translocation is also carried by his maternal grandmother and two of the mother's brothers.

The malformation syndrome consisted of unusual facial appearance and anomalies of the musculoskeletal, cardiovascular, genitourinary, and central nervous systems.

Four previously reported patients had similar break points on chromosome 12 with similar malformations; therefore, phenotype‐karyotype correlation suggests a definitive malformation syndrome associated with duplication of chromosome region 12q24.1→qter.
A cost‐benefit analysis of prenatal detection of down syndrome and neural tube defects in older mothers
Authors: Sadovnick A. D. , Baird P. A. , Opitz John M.
Published: June 2005

Infants of older mothers have an increased risk of Down syndrome. As public awareness of this disorder increases, so does the number of women requesting prenatal diagnosis for advanced maternal age. A cost‐benefit analysis was done to determine the maternal age for which screening for Down syndrome is costbeneficial. The analysis took into account the cases of neural tube defects which would be detected “incidentally” on amniocentesis, as all amniotic fluid samples have alpha fetoprotein levels measured. British Columbia (B.C.) provides a unique opportunity for such a study: single‐year maternal age risk figures for Down syndrome based on virtually complete ascertainment are available; the Department of Medical Genetics Prenatal Diagnosis Clinic is the main referral centre for the province; B.C. has a universal medicare system which facilitates the calculation of medical costs and gives all women financially equal access to prenatal diagnosis. The study concludes that prenatal screening for Down syndrome is cost beneficial for women 34 years old or older at conception. A discount rate of 14% was chosen for this analysis and the effect of such a rate on the results is discussed.