bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential diagnosis of Nager acrofacial dysostosis syndrome: Report of four patients with Nager syndrome and discussion of other related syndromes
Authors: Halal Fahed , Herrmann Jürgen , Pallister Philip D. , Opitz John M. , Desgranges Marie‐Françoise , Grenier Gilles , Fraser F. Clarke
Published: June 2005

We report four patients with Nager acrofacial dysostosis (AFD) syndrome and review all previous cases. This leads to an extended characterization of the Nager syndrome—eg, description of lower limb defects—and also to a discussion of the differential diagnosis which includes AFD postaxial defect syndrome, Fontaine syndrome, distal 2q duplication syndrome, hemifacial microsomia/Goldenhar radial defect syndrome, and some others.
Odontoonychodermal dysplasia: A previously apparently undescribed ectodermal dysplasia
Authors: Fadhil Mahmoud , Ghabra Tarek A. , Deeb Mary , Der Kaloustian Vazken M. , Opitz John M.
Published: June 2005

Seven affected individuals in a total of 24 belonging to three inbred Lebanese sibships are presented as having a previously apparently undescribed pure ectodermal dysplasia. For this condition, probably owing to the homozygous state of an autosomal recessive gene, we suggest the name trichoodontodermal dysplasia.
Variability in the Smith‐Lemli‐Opitz syndrome: Overlap with the meckel syndrome
Authors: Lowry R. B. , Opitz John M.
Published: June 2005

The syndromes of Smith‐Lemli‐Opitz (RSH) and of Meckel are usually clinically distinct but have many overlapping manifestations. In rare instances it may be difficult to distinguish them, especially if an autopsy is not done. Attention to detail is essential for accurate delineation. Two other syndromes, the C and Hydrolethalus, should be considered in the differential diagnosis.
Short rib‐polydactyly syndrome, Majewski type
Authors: Walley Virginia M. , Coates Charles F. , Gilbert Joseph J. , Valentine G. Howard , Davies Eleanor M. , Herrmann Jürgen
Published: June 2005

We describe a baby with external and internal anomalies of the Majewski form of the short rib‐polydactyly (SRP) syndromes. Previously unreported abnormal vertebral bodies, delayed ossification of the sternum and fibulae, and a diencephalic hamartoma are noted. These abnormalities and minimal histologic abnormality at the chondro‐osseous junction suggest that this syndrome may be heterogenous or more variable than previously known.
Fryns syndrome: A new variable multiple congenital anomaly (MCA) syndrome
Authors: Lubinsky Mark , Severn Charles , Rapoport Joseph M. , Opitz John M.
Published: June 2005

We report a brother and sister who died neonatally with a distinctive but variable multiple congenital anomaly (MCA) syndrome. Anomalies in both included similar facial changes, cleft palate, distal digital hypoplasia, lung hypoplasia, and urogenital abnormalities. They were discordant for cleft lip, diaphragmatic hernia, and Dandy‐Walker anomaly. These sibs resemble three recently reported stillborn children and support the existence of a “new” autosomal recessive MCA syndrome with variable expressivity.
Autosomal dominant duplication of the renal collecting system, hearing loss, and external ear anomalies: A new syndrome?
Authors: Fraser F. C. , Aymé S. , Halal F. , Sproule J. , Opitz John M.
Published: June 2005

We report two families in which propositi had severe bilateral sensorineural hearing loss, a preauricular pit or tag, and duplication of the ureters or bifid renal pelvices. Other relatives had one or more of these anomalies in a pattern suggesting autosomal dominant inheritance with reduced penetrance and variable expressivity. We suggest the term “branchio‐oto‐ureteral syndrome” to designate this condition.
The search for heterogeneity in insulin‐dependent diabetes mellitus: Evidence for familial and nonfamilial forms
Authors: Greenberg David A. , Anderson Carol E. , Qpitz John M.
Published: June 2005

Using five different published sets of data, we looked at the distribution of HLA‐DR genotypes among diabetic probands. It was possible to reject dominant inheritance at the HLA‐associated locus, but some of the data were compatible with recessive inheritance while some were not. An attempt to reconcile the conflicting data by proposing a three‐allele model apparently failed. It proved possible to resolve some of the conflicting data by proposing that simplex families represent primarily a recessive form of insulin dependent diabetes mellitus (IDDM) while multiplex families represent primarily two other subforms: one showing three‐allele inheritance and one not. We also propose that the HLA locus involved in IDDM mediates the effect of an environmental agent on a second disease locus.
Specific terminal DNA replication sequence of X chromosomes in different tissues of a live‐born triploid infant
Authors: Yu C. W. , Chen H. , Fowler M. , Opitz John M.
Published: June 2005

Using the thymidine pulse method, DNA replication kinetics were studied on cells derived from cartilage, gonad, lymphocytes, and skin of a live‐born triploid (69,XXY) infant with typical clinical findings. Replication studies showed that 3% of the lymphocytes had one early and one late replicating X, and 97% of the lymphocytes, and cartilage, gonad, and skin cells had two early replicating X's. Asynchronous DNA replication between the two early replicating. X's was observed in all tissues (range 25–40%). The predominant terminal replication sequence of X chromosomes from chondrocytes, gonad, and skin fibroblast differed from that of the lymphocytes. Thus, a tissue‐specific DNA replication pattern of the early‐replicating X chromosome may be present. In every tissue, the last band to complete DNA replication was Xq21. Polymorphisms of metaphase chromosomes of parents and the patient were studied by Q‐banding. The possible origin of the extra haploid set of chromosomes is discussed.
Extensions to pedigree analysis. IV. Covariance components models for multivariate traits
Authors: Lange Kenneth , Boehnke Michael , Opitz John M.
Published: June 2005

Often more than one quantitative trait is measured on each person in a set of pedigrees. The present paper suggests a class of covariance components models that will allow investigators to explore the genetic and environmental relationships between two quantitative traits. The theoretical framework for the models is given and criticized. We also discuss specific maximum likelihood methods for parameter estimation and hypothesis testing.
Nonimmune fetal hydrops and down syndrome
Authors: Fujimoto Atsuko , Broom Diane L. , Shinno Nancy W. , Wilson Miriam G. , Opitz John M.
Published: June 2005

Six infants with nonimmune fetal hydrops (NIFH) were found to have trisomy 21 (Down syndrome). A cardiac malformation was present in three of these infants. The manifestations of Down syndrome were obscured by the generalized edema at birth. The association of Down syndrome and NIFH emphasizes the need for chromosome analysis in the workup of infants or fetuses with NIFH.
The syndrome of Yunis and Varón—report of a further case
Authors: Hughes H. E. , Partington M. W.
Published: June 2005

We describe a boy with short stature, mental retardation, microcephaly, micrognathia, sparse hair, hypoplastic fingers and thumbs, distal aphalangia of the toes, and a hypoplastic clavicle. The pattern of anomalies corresponds closely to that found in five other children by Yunis and Varón.
Craniotelencephalic dysplasia in sisters: Further delineation of a possible syndrome
Authors: Hughes H. E. , Harwood‐Nash D. C. , Becker L. E. , Opitz John M.
Published: June 2005

We describe two sisters with a complex of anomalies involving the cranium and brain. The changes in the former are consistent with those previously described as craniotelencephalic dysplasia and those in the latter indicate primary developmental abnormalities of the central nervous system including septo‐optic dysplasia, absent olfactory nerves, agenesis of the corpus callosum, and lissencephaly. Per se, these cerebral malformations are causally heterogeneous, but their occurrence in association with craniotelencephalic dysplasia suggests that this combination is a distinct, probably autosomal recessive, syndrome.
An X;9 translocation, primary amenorrhea, and hypothalamic dysfunction
Authors: Gardner H. A. , McConnon J. K. , Mackenzie M. A. , Opitz John M.
Published: June 2005

A white girl presented at age 16 yr with delayed puberty and primary amenorrhea. She had 46 chromosomes with a de novo reciprocal X;9 translocation. The normal X chromosome was found to be heterochromatic, thus preserving the function of the translocation portion of the 9. Her total estrogen and serum estradiol levels were low and her serum follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) levels were at the lower end of the normal adult range. She had a reasonably good FSH and LH response to GnRH, but an inadequate response to 100 mg of clomiphene daily for 1 wk. This would suggest that the abnormality of function is probably hypothalamic, a hitherto unreported association.

De novo translocations between X chromosomes and autosomes are rare and none identical to this case has been described. The breakpoint of the X chromosome was at p22, well outside the “critical region” for female reproductive function. It seems probable that her chromosome abnormality is responsible for her clinical state.
Familial agnathia‐holoprosencephaly
Authors: Pauli Richard M. , Pettersen James C. , Arya Sunita , Gilbert Enid F. , Opitz John M.
Published: June 2005

Two stillborn sisters had characteristics of both agnathia and holoprosencephaly. Familial occurrence implies that agnathia‐holoprosencephaly may be determined by a single recessive gene, something to be taken into account when counseling such families. Evidence from human experience and various animal models suggests that agnathia‐holoprosencephaly represents a causally heterogeneous single developmental field defect. Anatomical studies of these two stillborn sisters support the view that they shared a developmental field defect which affected structures in the face, cranial cavity, and upper neck. The pathogenesis of these variably expressed defects probably relates to defects in neural crest cells of cranial origin and/or to underlying mesodermal support elements of these cells.
The diagnosis and frequency of X‐linked conditions in a cohort of moderately retarded males with affected brothers
Authors: Fishburn Jane , Turner Gillian , Daniel Art , Brookwell Ross , Opitz John M.
Published: June 2005

An epidemiological study was carried out on the group of moderately retarded brothers (IQ, 30–55) identified by Turner and Turner [1974]. Of the original 58 sets of brothers, 54 sets (now 17 to 32 years old) were traced; another four sets (missed in the earlier survey) were added. Forty‐five of the 58 pairs were diagnosed as having nonspecific X‐linked mental retardation (MR) giving an overall frequency of 5.57 moderately retarded males/10,000 male births. In 12 of the 45 families, affected males had the fragile(X) and macroorchidism; six had macroorchidism alone, giving a frequency of 2.8 moderately retarded males with X‐linked MR and macroorchidism ± the fragile(X) per 10,000 males. Corresponding heterozygote frequencies are 7.34 and 3.65/10,000 females respectively. A new subgrouping of nonspecific X‐linked mental retardation is described in six families: X‐linked MR, macroorchidism without the fragile(X). Three other X‐linked conditions were identified: in one family, the Coffin‐Lowry syndrome, in another, Duchenne muscular dystrophy, and in two families X‐linked MR and muscle atrophy. Half (56%) of the obligatory carriers of fra(X)‐MR in this study were dull to mildly retarded. The mildly retarded heterozygotes had a significantly higher percentage of fra(X) expressing lymphocytes as compared to the intellectually normal heterozygotes. When the three types of nonspecific X‐linked MR for which population frequencies were calculated were considered together, half of the obligatory carriers (46%) were dull or mildly retarded, thus confirming that this condition is a significant cause of mild intellectual handicap in females.
Autosomal dominant inheritance of the Aarskog syndrome
Authors: Grier Robert E. , Farrington Frank H. , Kendig Robert , Mamunes Peter , Opitz John M.
Published: June 2005

Individuals with the Aarskog syndrome have shortness of stature, round face, hypertelorism, short fingers and hands, and flat feet; males have a shawl scrotum. Pedigrees have consistently suggested X‐linked inheritance, although the possibility of autosomal dominant inheritance was not excluded. We present a father and two sons affected with the Aarskog syndrome. Thus, the Aarskog phenotype either is genetically heterogeneous or a sex‐influenced autosomal dominant trait as shown by the deficiency of affected females. An ascertainment bias for males could be owing to the shawl scrotum. We have reviewed the literature and tabulated findings in 82 previously reported cases.
Inheritance of Bartter syndrome
Authors: Pereira R. Rodrigues , van Wersch J. , Opitz John M.
Published: June 2005

The Bartter syndrome is regarded as an autosomal recessive trait because of sib occurrence, equal sex ratio, and normal parents. Recently, obligatory carriers were shown to have the same pattern of platelet aggregation inhibition as their affected children, possibly a reflection of altered prostaglandin action. We investigated eight patients, and their parents and sibs, and found that all persons included in the study had impaired thrombocyte aggregation. These aggregation studies support the hypothesis that the Bartter syndrome is an autosomal recessive trait.
Intracranial aneurysms: A report of a large pedigree
Authors: Halal Fahed , Mohr Gérard , Toussi Tahmouresse , Martinez S. Napoléon
Published: June 2005

We report on the occurrence of intracranial aneurysms in several individuals of a large French‐Canadian family. Recurrence risk from 22 previously reported families (each with at least two affected first degree relatives) and the present family does not allow any firm conclusion about the mode of inheritance of the trait.
Paternity testing: I. Calculation of paternity indexes
Authors: Kaiser L. , Seber G. A. F. , Opitz John M.
Published: June 2005

An algorithm, readily adaptable to microcomputers, is given for computing paternity indexes. A closed‐form expression based only on gene frequencies and phenotype structures is derived for the paternity index for a given mother/child/alleged father trio and any blood group system. This above work is applied to the problem of estimating gene frequencies from sample data.
Prenatal diagnosis in two pregnancies of an achondroplastic woman
Authors: Elejalde B. Rafael , de Elejalde Maria Mercedes , Hamilton Phillip R. , Lombardi Joseph M. , Opitz John M.
Published: June 2005

We present the results of the ultrasonographic examination of two successive pregnancies of an achondroplastic woman. The limb bones were measured and shown to be normal in length. Other pertinent literature reports are discussed.
The origin of inverted tandem duplications, and phenotypic effects of tandem duplication of the X chromosome long arm
Authors: Van Dyke Daniel L. , Miller Michael J. , Weiss Lester , Opitz John M.
Published: June 2005

Tandem repeats of chromosome material can arise as inverted or as direct duplications. Such duplications of the X chromosome are instructive regarding X‐linked genetic determinants of phenotype. We describe a 40‐year‐old woman with a direct duplication Xq13.3 to Xq27.2, short stature, gonadal dysgenesis, and secondary amenorrhea. Comparison of her phenotype with that of two other women with a direct duplication of part of Xq confirms the existence of statural determinants within the region X13 to Xq21, determinants of ovarian function within X22 to X27, and the X inactivation center within or proximal to band Xq13.3.

In humans, direct duplications are more frequent than inverted, but both forms are rare. The mean age of parents is normal in subjects with direct duplications, but is advanced in subjects with inverted duplications. An inverted duplication can arise from a three‐break rearrangement that includes a U‐type exchange; a similar origin (two breaks and a U‐type exchange) and a parental age association can be postulated for dicentric inverted duplications including dicentric isochromosome X.
A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism
Authors: Johnson Virginia P. , McMillin J. Michael , Aceto Thomas , Bruins George , John M.
Published: June 2005

We describe a large, three generation kindred in which 16 individuals were affected with alopecia, hyposmia or anosmia, conductive deafness associated with protruding ears, microtia, and/or atresia of the external auditory canal, hypogonadotropic hypogonadism due to LH/FSH deficiency, and a greater than normal tendency to dental caries. Variable manifestations include mild facial asymmetry, mental retardation, congenital heart defect, and cleft palate. This seems to be a previously undescribed pleiotropic autosomal dominant trait with variable expressivity.

The manifestations can be explained on the basis of involvement of the ectoderm and neuroectoderm of the first and second branchial arches, of Rathke's pouch, and of the diencephalon.
Part I. Amyoplasia: A common, sporadic condition with congenital contractures
Authors: Hall J. G. , Reed S. D. , Driscoll E. P. , Opitz John M.
Published: June 2005

A specific congenital contracture (arthrogryposis) syndrome has been recognized in 135 out of 350 patients with various kinds of congenital contractures. This sporadic syndrome, designated amyoplasia is characterized by absence of limb muscles that are replaced by fibrous and fatty tissue. At birth there is characteristic positioning of the limbs with internal rotation at shoulders, extension at elbows, and flexion of the hands at the wrists. Severe equinovarus deformities of the feet are usually present. Contractures at knees and hips occur in a variety of positions. Typically, the face is round with a frontal midline capillary hemangioma and slightly small jaw. Intelligence is normal.

Approximately 63% of our patients had involvement of four limbs (almost always symmetrically), 24% mainly of lower limbs, and 13% mainly upper limbs. Typically, no other malformations are present. However, minor anomalies are seen often, and include hypoplastic digits and hypoplasia of scrotum or labia, the umbilical cord may be wrapped about a limb at birth. In utero fetal activity is decreased and breech delivery is increased in amyoplasia. All cases were sporadic; identical twins are discordantly affected.
Neural tube defects in the Sikhs
Authors: Baird P. A.
Published: June 2005

Background information on the incidence of neural tube defects (NTD) in Sikhs in India and elsewhere is given. The incidence of NTD in the Sikh population of British Columbia is estimated for 4 years and found to be 2.86 per 1,000 births. The overall rate for NTD in all B.C. births for these same years is 1.26 per 1,000 births. This difference is statistically significant. Analysis of cases showed that a greater proportion of Sikh cases are stillborn, and these account for much of the excess over expected. It appears that the incidence of NTD in Sikhs is increased compared to the general population incidence of these birth defects in B.C.
Familial supernumerary microchromosome mosaicism: Phenotypic effects and an attempt at characterization
Authors: Chudley Albert E. , Zheng Huui‐Zu , Pabello Paulino D. , Shia George , Wang Hsi‐Chang , Opitz John M.
Published: June 2005

A healthy normally intelligent man and his two daughters who had mild developmental delay and different malformations were determined to have an acrocentric supernumerary microchromosome (MC). The father and both daughters were noted to be mosaic for the MC, perhaps suggesting mitotic instability of the MC cell line with loss over time. The MC was negative staining on G‐banding and showed absence of centromeric heterochromatin on C‐banding. A centromere was identified with silver staining; no NORs were identified. The MC approximated the size of the short arm of the Y chromosome and showed cytologic behavior similar to that of a Y chromosome. H‐Y antigen and Y‐DNA gene probe studies failed to confirm a Yp origin.
Conductive deafness, symphalangism, and facial abnormalities: The WL syndrome in a Japanese family
Authors: Higashi Koichiro , Inoue Shuichi
Published: June 2005

We report on a family in which four relatives were affected with an autosomal dominant syndrome of unusual facial appearance, nasal abnormality, conductive deafness, pectus carinatum, and symphalangism. This appears to be only the second report of the WL symphalangism syndrome of Herrmann and the first studied in a Japanese family.
Assessment of variance components models on pedigrees using cholesterol, low‐density, and high‐density lipoprotein measurements
Authors: Beaty T. H. , Self S. G. , Chase G. A. , Kwiterovich P. O. , Opitz John M.
Published: June 2005

Plasma total cholesterol, low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) measurements on 402 individuals in 62 randomly selected families from the Columbia Medical Plan population were used to select the “best” model among a series of multifactorial models using the maximum likelihood method described by Lange et al [1976]. These models included both genetic and non‐genetic components of variance. The most parsimonious model for each trait was selected and examined using a goodness‐of‐fit statistic designed by Hopper and Mathews [1982] to test the assumptions of this technique.

A simple additive genetic model was the most plausible for all three measurements, suggesting a strong role for genetic factors in determining lipid and lipoprotein levels in these data. Goodness‐of‐fit statistics for these models were examined and showed little evidence of deviation from the assumption of multivariate normality within pedigrees. This approach of selecting the most parsimonious model among a series of competing models and then assesing its goodness‐of‐fit has many applications in studying familial aggregation of quantitative traits.
A large kindred with X‐linked mental retardation, marker X and macroorchidism
Authors: Lubs Herbert , Travers Helen , Lujan Enrique , Carroll Andrew , Opitz John M.
Published: June 2005

Thirty‐eight members of a black kindred with mental retardation and the Marker X were studied. Ten of 14 affected males, 6 of 6 affected females, 18 carriers or possible carriers, and 7 normal males were examined. Eight of 9 affected males who could be measured had macroorchidism, but their ears and mandibles were not prominent. No distinct facies were evident, although minor anomalies, such as a slight pectus, were present in some. Clinical diagnosis in the absence of a strongly positive family history may be even more difficult among prepubertal black children than in whites. The risk of retardation among children of carriers was estimated at 20–40%.
An anthropometric study of males with the Fragile‐X syndrome
Authors: Meryash David L. , Cronk Christine E. , Sachs Benjamin , Gerald Park S. , Opitz John M.
Published: June 2005

Anthropometric methods were used to examine 18 males 18 to 69 years old with the Fragile‐X syndrome. Thirteen of 15 subjects had macroorchidism. The average height of the individuals with the Fragile‐X was less than that of published standards. Seventeen of the 18 subjects had absolute or relative macrocephaly, and two‐thirds of the subjects were dolichocephalic. For the group as a whole, facial and ear lengths were increased, and facial breadth, hand length, and foot length were decreased. It is suggested that relationships between various measurements of an individual may be more important than any single measurements for conveying the characteristic appearance of an individual with the Fragile‐X syndrome.
Fragile‐X syndrome III: Dermatoglyphic studies in males
Authors: Simpson Nancy E. , Newman B. J. , Partington M. W. , Opitz John M.
Published: June 2005

Dermatoglyphics of 39 males with the fragile‐X syndrome were compared with those of 3 groups of control subjects; 497 school boys, 15 males with non‐specific mental retardation, and 15 with Down syndrome. Compared with the control males, there was an increased frequency of radial loops, whorls, and arches on the fingers and of third interdigital patterns and abnormal creases on the hands, and a decreased frequency of ulnar loops and fourth interdigital patterns in the patients with the fragile‐X syndrome. The mean a‐b ridge count was lower than in controls and there were more patients than controls with an a‐b ridge count < 70. All of these differences were significant at p < 0.01. There was no difference between patients and controls with respect to total ridge count on the fingers and the dermatoglyphics in other areas of the hands or feet.

From this small study a preliminary index was developed that attempts to distinguish male patients with the fragile‐X syndrome from normal male controls and males with nonfragile‐X forms of mental retardation. The patterns on the left and right third fingers, the a‐b ridge count, and the palmar creases were used in the index. Sixty‐four % of patients with the fragile‐X syndrome would be selected out if ≥ + 0.5 was used as the criterion and 90% of these males would be expected to have the fragile‐X chromosome.
Folate metabolism in cells from fragile X syndrome patients and carriers
Authors: Wang Jin‐Chen C. , Erbe Richard W. , Opitz John M.
Published: June 2005

The in vitro folate sensitivity of the fragile site at Xq27 and the claims of a beneficial response of patients given folic acid prompted us to examine the folate metabolism in cells cultured from fragile X syndrome patients and carriers. Using Epstein‐Barr virus we established permanent lymphoblastoid lines from 4 fragile X syndrome males and 3 carriers from 7 families. All these lines expressed the fragile site when 0.1 μ M 5‐fluorodeoxyuridine(FUdR) was added to the cultures 24 hr prior to harvest; thus, the lines seemed suitable for seeking an intrinsic defect. Fragile X syndrome patient and carrier lines and normal control cell lines did not differ in regard to folate requirement for growth, the ability to use homocysteine in place of methionine, the ability to utilize reduced folates as the sole folate source, or methotrexate sensitivity. These results suggest that no intrinsic defect in folate metabolism is present in fragile X syndrome cells.
Neural tube defects as an X‐linked condition
Authors: Baraitser Michael , Burn John , Opitz John M.
Published: June 2005

We present a family in which a woman had 3 brothers and 3 sons with neural tube defects.
Dominant inheritance of bifid nose
Authors: Anyane‐Yeboa K. , Raifman M. A. , Berant M. , Frogel M. P. , Travers H. , Opitz John M.
Published: June 2005

To our knowledge, median cleft of nose without apparent hypertelorism (bifid nose) has been reported only twice [Esser, 1939; Boo‐chai, 1965]. We report five individuals in 3 generations of a family who had a bifid nose without apparent hypertelorism or mental retardation. In this family bifid nose was most likely an autosomal dominant trait.
Genetic analysis of sodium‐lithium countertransport in 10 hypertension‐prone kindreds
Authors: Dadone Mary M. , Hasstedt Sandra J. , Hunt Steven C. , Smith Jean B. , Ash K. Owen , Williams Roger R. , Opitz John M.
Published: June 2005

The rate of sodium‐lithium countertransport (SLC flux) across red cell membranes has been reported to be elevated in hypertensive persons and their relatives as compared to normotensive individuals without family histories of hypertension. We have investigated the inheritance of this trait in 434 persons from 10 kindreds. Relatives show positive correlation of SLC flux values, but there is no spouse‐spouse correlation. Pedigree analysis favors a model of polygenic inheritance over models of major‐gene inheritance. Major‐gene index statistics and offspring‐between‐parent statistics provide similar results. The proportion of total pheno‐typic variance that is attributable to polygenic differences between persons is estimated at 71%. The SLC flux values of hypertensive persons in this study population are lower than those reported from Boston, but are similar to those reported from Europe. We found a broad overlap of SLC flux values for hypertensive and normotensive persons. We conclude that SLC flux probably is not useful as a preclinical marker for essential hypertension.
Curry‐Hall syndrome
Authors: Shapiro S. D. , Jorgenson R. J. , Salinas C. F. , Opitz John M.
Published: June 2005

Curry and Hall [1979] described a large Spanish‐Mexican family with a pleiotropic autosomal dominant disorder of polydactyly, conical teeth, nail dysplasia, and short limbs. We describe a patient with similar manifestations, but from a different geographic and ethnic background. We propose that the disorder be called the Curry‐Hall syndrome.
Syndrome of multiple pterygia, camptodactyly, facial anomalies, hypoplastic lungs and heart, cystic hygroma, and skeletal anomalies: Delineation of a new entity and review of lethal forms of multiple pterygium syndrome
Authors: Chen H. , Immken L. , Lachman R. , Yang S. , Rimoin D. L. , Rightmire D. , Eteson D. , Stewart F. , Beemer F. A. , Opitz J. M. , Gilbert E. F. , Langer L. O. , Shapiro L. R. , Duncan P. A.
Published: June 2005

Three unrelated stillborn infants (cases 1–3) are presented here with a distinct constellation of multiple anomalies: namely, multiple pterygia involving chin‐to‐sternum, cervical, axillary, antecubital, crural and/or popliteal areas, flexion contractures of multiple joints, small chest, hydrops, characteristic abnormal facial appearance with hypertelorism, markedly flattened nasal bridge with hypoplastic nasal alae, cleft palate, micrognathia, apparently low‐set malformed ears, short neck with a cystic hygroma at the back of the neck and head, and pulmonary and cardiac hypoplasia.

Radiographic studies, in addition, showed scalp edema, microbrachycephaly, flattened mandibular angle, lack of normal curvature at the cervico‐thoracic junction, marked bony fusion of posterior spinous processes of older fetuses (cases 1, 2), thin crowded ribs, markedly hypoplastic scapulae, hypoplastic iliac wings, ischia and pubic bones, undermodeling of tubular bones, and radio‐ulnar synostosis.

Histologic studies of the skeletal system showed cartilaginous and bony fusion of the spinous processes (cases 1, 2), fusion of epiphyseal cartilages of distal humerus and proximal ulna, a poorly developed joint space, an abnormal growth plate, and weak safranin staining ofthe resting cartilages (cases 1, 2).

To the best of our knowledge, this pattern of anomalies constitutes a previously undescribed syndrome. Prenatal diagnosis of this entity is possible by ultrasonographic studies on the basis of nonimmune fetal hydrops, a cystic hygroma at the back of the head and neck, diminished fetal activity, short and fixed limbs, and/or maternal hydramnios. Three additional cases (cases 4–6) are also presented to show a possible heterogeneity of this syndrome.
Lethal multiple pterygium syndrome
Authors: Van Regemorter N. , Wilkin P. , Englert Y. , El Khazen N. , Alexander S. , Rodesch F. , Milaire J.
Published: June 2005

We report on two fetuses with a lethal form of multiple‐pterygium syndrome born to first cousins. The two pregnancies aborted spontaneously in the 2nd trimester, the fetuses, 10–11 weeks of embryonic age, showing multiple pterygia and multiple cartilaginous fusions. One had cleft lip and palate. In both cases the microscopic anatomy of the placenta showed villi with scalloped border and intravillous trophoblastic invaginations.
Prenatal diagnosis of thanatophoric dysplasia at 24 weeks
Authors: Camera Gianni , Dodero Danilo , De Pascale Sergio
Published: June 2005

We report making the prenatal diagnosis of thanatophoric dysplasia at 24 weeks gestation. The ultrasound examination showed short limbs. By in utero radiological study, we could see the typical changes of this skeletal dysplasia. Radiological and histological studies confirmed the aborted fetus to be affected with thanatophoric dysplasia.
Duplication of part of chromosome 1q: Clinical report and review of literature
Authors: Michels Virginia V. , Berseth Carol Lynn , O'Brien John F. , Dewald Gordon , Opitz John M.
Published: June 2005

We report a male infant with a 47,XY,+der(22),t(1;22)(q32;q11)pat karyotype. Thus, he has duplication of chromosomes 1(q32→qter) and 22(pter→q11). Six patients with dup 1(q32→qter) and eight with dup 1(q42→qter) have been described. These two groups of patients share several manifestations, including postnatal growth retardation; relative macrocephaly with widely separated sutures or large fontanelles; prominent forehead; highly arched palate; micrognathia; downward slant of the palpebral fissures; broad, flat nasal bridge; and apparently low‐set, malformed ears. Although many of these abnormalities are nonspecific, partial duplication of 1q should be considered in infants with relative macrocephaly, large fontanelles, and downward slant of the palpebral fissures. Our patient had duplication of the part of chromosome 22 that may be associated with the clinically variable cat‐eye syndrome. Patients with dup 22(pter→q11) may also have downward slant of the palpebral fissures, micrognathia, and apparently low‐set, malformed ears. The structural gene locus for β‐glucosidase has been mapped to chromosome 1. β‐Glucosidase activity in fibroblasts from our patient was normal, and his parents' activities were not significantly different from those of control individuals. Therefore, either the locus for this enzyme is not present on 1(q32→qter) or the enzyme does not consistently show a substantial gene‐dose effect.
Multiple synostosis syndrome: Study of a large Brazilian kindred
Authors: da‐Silva Elias O. , Filho Sílvio M. , de Albuquerque Sílvio C.
Published: June 2005

We report a large Brazilian kindred with 28 cases of the autosomal dominant multiple synostosis syndrome. The main anomalies were symphalangism and carpal and tarsal synostoses. Other common findings included synostosis involving other bones, absence of phalanges and nails, short metacarpals, pes planovalgus with prominent lateral border, hypoplastic alae of nose, short upper lip, and dermatoglyphic abnormalities. This may be a variant of the WL syndrome.
Genetic heterogeneity in spondyloepiphyseal dysplasia congenita
Authors: Harrod Mary Jo E. , Friedman Jan M. , Currarino Guido , Pauli Richard M. , Langer Leonard O. , Opitz John M.
Published: June 2005

Two unrelated infants seen for evaluation of short stature at 14 and 27 months, respectively, had clinical and radiographic findings consistent with the diagnosis of spondyloepiphyseal dysplasia congenita (SED congenita). No other anomalies were noted. Both sets of parents were normal, both family histories were unremarkable, and neither couple was consanguineous. Both families were counseled that SED congenita is an autosomal dominant disorder and that sporadic cases proably result from new mutations; a low recurrence risk was given. Both families subsequently produced a second affected child. Our experiences suggest that genocopies of autosomal dominant SED congenita exist that are clinically and radiographically indistinguishable, at least within the first 3 years. Autosomal recessive inheritance seems most likely, although alternative explanations are possible. Genetic heterogeneity should be considered when providing genetic counseling for sporadic SED congenita in young children.
The Jansen type of metaphyseal chondrodysplasia: Confirmation of dominant inheritance and review of radiographic manifestations in the newborn and adult
Authors: Charrow Joel , Poznanski Andrew K. , Opitz John M.
Published: June 2005

We describe a mother and infant girl with the Jansen type of metaphyseal chondrodysplasia. The transmission of the syndrome from mother to daughter in this family establishes this as a dominant condition. Characteristic radiographic manifestations of the disorder were obvious at birth. The mother and infant illustrate the two extremes of age where the radiographic manifestations are less characteristic than in middle childhood, since the marked metaphyseal calcifications are absent.
A possible explanation for the low incidence of gonosomal aneuploidy among the offspring of triplo‐X individuals
Authors: Neri Giovanni , Opitz John M.
Published: June 2005

A review of the reproductive performance of 47,XXX individuals showed that the incidence of gonosomal aneuploidy among the offspring is low. To explain this unexpected phenomenon it is hypothesized that fertile triplo‐X individuals have chromosomally normal oogonia due to mitotic nondisjunction in a cell from which the primordial germ line took origin. Mosaic 46,XX/47,XXX individuals have a somewhat higher risk of bearing aneuploid offspring, possibly due to a constitutional tendency toward gonosomal nondisjunction.
Inbreeding effect on morbidity: I. Three Analyses (one with cousin and sib controls) of two surveys among Brazilian whites and Negroes
Authors: Ruas P. M. , Freire‐Maia N.
Published: June 2005

Data from two surveys performed in Brazil and involving 5,719 persons have been subdivided into three subsamples (one with cousin and sib controls). The totals led to estimates of B (abnormal equivalents per gamete) around 0.5, of A (the damage in a noninbred population) around 0.01–0.02, and of B/A from 14 to 77. No statistically significant difference was found between whites and nonwhites (mulattoes and Negroes). Inbreeding seems to disclose a predominantly mutational load.
Stability over time of hematological variables in 197 children with sickle cell anemia
Authors: Odenheimer Daniel J. , Whitten Charles F. , Rucknagel Donald A. , Sarnaik Sharada A. , Sing Charles F.
Published: June 2005

One hundred ninety‐seven children with sickle cell anemia were followed for 4 years at the Wayne State Comprehensive Sickle Cell Center to evaluate the stability of the hematological variables (Hb, Hct, RBC count, MCV, %HbF and %HBA2) over time. The mean values of the hematological measurements taken during three separate 16‐month intervals were used to represent an individual's values. The correlations of the hematological variables between intervals ranged from a low of 0.46 for %HBA2 to a high of 0.91 for %HbF. Correlations that spanned two intervals (an average of 32 months) were of the same magnitude as those that spanned only one interval (an average of 16 months), suggesting that there was no decrease in the degree of stability of these variables as the time between measurements increased. The stability of the correlations between variables within intervals, and the stability of the coefficients of the first two principal components of the six hematological variables over time suggested that the relationships among variables were also stable.

In a recent report [Odenheimer et al, 1983], we used the values of the six hematological variables collected at an individual's first visit to the sickle cell center to identify four hematologically distinct subgroups of children. In the current report, we found that as many as 83% of the individuals remained in the same subgroup in at least two of the three follow‐up intervals, suggesting that the factors that contributed to this classification were the result of stable, rather than transient phenomena.
The commemoration of the Meckel bicentennial: Bozeman 1982
Authors: Mullen Pierce C.
Published: June 2005

Under close scrutiny the perogative of self‐intelligibility thus attributed to present time is found to be based upon a set of strange postulates. In the first place, it supposes that, within a generation or two, human affairs have undergone a change which is not merely rapid, but total, so that no institution of long standing, no traditional form of conduct, could have escaped the revolutions of the laboratory and the factory. It overlooks the force of inertia peculiar to so many social creations.
Meckel syndrome in different populations
Authors: Lurie Iosif W. , Prytkov Alexander N. , Meldere Lyudmila V. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on 18 infants from 13 families where the infant was affected with the Meckel syndrome. The parents belong to various national groups—Russians, Byelorussians, Poles, Ukrainians, Letts, and Tatars. One child was from an incestuous union (half‐sister and half‐brother), in 4 families the parents were natives of the same or neighboring villages; other parents apparently were not related. Excluding 3 couples from Central Russia, the Ukraine, and Tatary, the other 10 families were the inhabitants of the Moscow region, Byelorussia, and Latvia. In 3 of these families at least one grandparent was of Tatar descent. At the same time the frequency of Tatars in these regions is less than 1%. Using the Newton binomial distribution it was shown that the hypothesis about equal frequency of the Meckel syndrome gene among Tatars and other national groups under study may be excluded completely, and therefore the alternative hypothesis about an unusually high frequency of this gene among Tatars must be accepted. Such analysis may be useful for comparative evaluation of gene frequencies in populations which cannot be studied directly.
Genetic counseling in Becker type X‐linked muscular dystrophy. I. Theoretical considerations
Authors: Grimm T. , Opitz John M. , Reynolds James F.
Published: June 2005

The prior probability of any woman being a carrier for Becker muscular dystrophy (BMD) has been calculated. If μ is the mutation rate in female germ cells and n̈ the mutation rate in male germ cells, this probability is 34/3μ + 20/3v. For all X‐linked diseases with a fitness f the prior probability (H) is:
Familial t (4;21)(q2.4;q2.2) leading to unbalanced offspring with partial duplication of 4q and of 21q without manifestations of the down syndrome
Authors: Kitsiou‐Tzeli Sophia , Hallett Joseph J. , Atkins Leonard , Latt Samuel A. , Holmes Lewis B. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on an infant with a malformation syndrome who had a combination of partial duplication of 4q and 21q as the result of a maternal unbalanced translocation. She has duplication of the proximal portion of chromosome 21, without manifestation of the Down syndrome.
Manifestations of pseudoxanthoma elasticum during pregnancy: A case report and review of the literature
Authors: Elejalde B. Rafael , de Elejalde Maria Mercedes , Samter Thomas , Burgess John , Lombardi Joseph , Gilbert Enid F. , Opitz John M. , Reynolds James F.
Published: June 2005

A 30‐year‐old white woman with pseudoxanthoma elasticum (PXE) was followed throughout her pregnancy with several fetal ultrasonographic examinations and other diagnostic studies; these showed normal development up to the 26th wk and then a marked deceleration of fetal growth. The ultrasonographic appearance of the placenta was abnormal at all times probably related to the microscopic changes. The baby, born at 36 wk, showed severe intrauterine growth retardation as a probable consequence of the abnormal placenta detected by ultrasound and corroborated at birth. The cotyledons were small and more numerous than normal. One third of the placenta was hypoplastic or atrophic, with focal calcification in septa, stroma, villi, and decidua, and increased deposition of fibrin around villi. The most striking change was the increased number of septa and the abnormal elastic tissue.
Genetic analysis of cleft lip with or without cleft palate in Danish kindreds
Authors: Marazita Mary L. , Spence M. Anne , Melnick Michael
Published: June 2005

The present study population consist of 2,532 families ascertained through nonsyndromic cleft lip with or without cleft palate (CL ± P) surgical probands born in Denmark between 1941 and 1971. Three samples were derived for analyses of the trait “Clefted (CL ± P) or not.” Sample 1 consists of the4 26 largest multigenerational families with four or more affected members. Both samples 2‐MG and 2‐N consist of nuclear families with at least two children and at least one proband among the children. Sample 2‐mG contains 846 nuclear families derived from the kindreds with three or more generations. Sample 2‐N contains a further 1,181 kindreds with only two generations, nuclear family information available.

Four methods of analysis were used: (1) Pedigree analysis was performed on each of the multigenerational kindreds of Sample 1. Results were consistent with autosomal recessive inheritance in eight families and codominant inheritance in three families. These simple genetic hypotheses could not be distinguished in the remaining 15 families. (2) The Goodness‐of‐fit of the multifactorial threshold (MF/T) model was tested in Samples 2‐MG, and 2‐N. The MF/T model was rejected in both samples. (3) Classical segregation analysis was performed on Samples 2‐MG and 2‐N. Results were consistent with a possible recessive major gene for CL ± P in Sample 2‐MG, but not in Sample 2‐N, and with significant admixture of sporadic cases in both samples. (4) Complex segregation analysis under the mixed model was performed on Samples 2‐MG and 2‐N, In sample 2‐MG, results were consistent with either the general mixed model or with an hypothesis of no major gene. In Sample 2‐N, four hypotheses were equally likely: the mixed model with no polygenic component, the mixed model with the major gene component, the mixed model with no sib environmental correlation, and major gene alone.

Three conclusions may be drawn: (1) The data provide no support for the MF/T model. (2) The data are consistent with the possibility of a major gene in a portion of the kindreds. (3) The data provide evidence for genetic heterogeneity for CL ± P.
Opsismodysplasia: A new type of chondrodysplasia with predominant involvement of the bones of the hand and the vertebrae
Authors: Maroteaux Pierre , Stanescu Victor , Stanescu Ritta , Le Marec Bernard , Moraine Claude , Lejarraga Horacio
Published: June 2005

The name opsismodysplasia is proposed for a new chondrodysplasia, which was studied in three patients. Clinically, the condition is recognized at birth on the basis of shortness, short hands, and facial abnormalities with a short nose and a depressed bridge of nose. The most characteristic radiographic signs are: very retarded bone maturation; marked shortness of the bones of the hands and of the feet with concave metaphyses; and thin, lamellar vertebral bodies. The growth cartilage studied in one case showed a wide hypertrophic area containing thick connective tissue septa, irregular provisional calcification, and vascular invasion. Type I collagen was detected in the hypertrophic area by immunohistochemical and microchemical tests. The transmission of opsismodysplasia is probably autosomal recessive.
GAPO syndrome: Report of three affected brothers
Authors: Gagliardi Antonio Ricardo T. , Gonzalez Claudette Hajaj , Pratesi Riccardo
Published: June 2005

We present a sibship of three brothers affected with the GAPO syndrome. This is a rare and very characteristic autosomal‐recessive trait whose main manifestations are growth retardation, alopecia, pseudo anodontia, and optic atrophy. So far nine affected individuals are known (4 males and 5 females). Two of them, the patient of Andersen and Pindborg cited in Tipton and Gorlin [1983] and one of the cases of Wajntal et al [1982], died at 39 and 37 years respectively.