bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic causes of chronic musculoskeletal disease in childhood are common
Authors: Gregory Diana , Kaplan Paige , Scriver Charles R.
Published: June 2005

We surveyed admissions to a pediatric orthopedics hospital for calender years 1957 (polio era) and 1982 (post‐polio era). The relative importance of genetic causes of musculoskeletal disease increased after poliomyelitis immunization became universal. Admissions for musculoskeletal disease with a genetic cause (chromosomal, Mendelian, multifactorial, and familial) accounted for 45% of the total in 1957 and 57% in 1982 (p < 0.02); non‐genetic causes were 44% in 1957 and 28% in 1982 (p < 0.001). The high probability of recurrent disease in the families of these patients implies that genetics has an important place in the provision of services and in the education of staff in pediatric orthopedic hospitals.
Clinical and biochemical characteristics of prolidase deficiency in siblings
Authors: Freij Bishara J. , Levy Harvey L. , Dudin Gertrud , Mutasim Diya' , Deeb Mary , Der Kaloustian Vazken M.
Published: June 2005

Two brothers with recurrent skin ulcers of the lower limbs, subnormal intelligence, developmental abnormalities, and poliosis were found to excrete large quantities of several imidodipeptides in their urine. Glycylproline was the most prominent imidodipeptide excreted and was also detected in their blood. Prolidase activity was markedly deficient in red blood cells from both patients (4.1% and 3.7% of control mean) and skin fibroblasts from the one brother so examined (3.7% of control mean). A total of 20 patients with prolidase deficiency, including the two in this report, have been described in the literature. Their manifestations and various attempts at treatment are reviewed.
Genetic linkage analysis of epidermolysis bullosa simplex, Köbner type
Authors: Mulley J. C. , Nicholls C. M. , Propert D. N. , Turner T. , Sutherland G. R.
Published: June 2005

Genetic linkage relationships between a range of marker loci and the locus for epidermolysis bullosa simplex (EBS), Köbner type, were examined in a single kindred. A positive lod score of 1.2 at θ = 0.2 was found for Fy. To test the clinical observation that Köbner and Weber‐Cockayne types may be the same disease determined by different alleles, published lod scores from definite Weber‐Cockayne families were added to those from this study. A lod score of 1.8 was found at θ = 0.2. This value falls to 1.5 at θ = 0.2 when all families other than Ogna type are included. The Köbner variant studied is not closely linked to GPT and is therefore distinct from EBS1 (Ogna type). Linkage analysis is consistent with an hypothesis that Köbner and Weber‐Cockayne types are determined by a single locus; however, further evidence is needed before this locus can be designated EBS2 and assigned to chromosome 1.
An autosomal recessive disorder with glomerular basement membrane abnormalities similar to those seen in the nail patella syndrome: Report of a kindred
Authors: Salcedo Jose R.
Published: June 2005

We present a 9‐year‐old boy, the product of a consanguineous marriage, with proteinuria, edema, and microscopic hematuria with mild renal impairment since age 2 yr. Renal biopsy showed the histopathologic electron microscopic changes seen in hereditary osteo‐onchyodysplasia (HOOD) [Hoyer et al, 1972; Bennet et al, 1973; DelPozo and Lapp 1970; Vernier et al, 1974; Morita et al, 1973] or “nail‐patella syndrome.” Neither the patient nor his relatives had bone or nail abnormalities; however, 2 other sibs had died of complications of end‐state renal disease at age 6 and 9, leading us to suspect autosomal recessive inheritance of a severe nephropathy or glomerulodysplasia.
Biochemical genetics of the Lapland dog model of glycogen storage disease type II (acid α‐glucosidase deficiency)
Authors: Walvoort Hendrik C. , Slee Regina G. , Sluis Koos J. , Koster Johan F. , Reuser Arnold J. J.
Published: June 2005

A recently described canine model (Lapland dog) of glycogen storage disease type II (GSD II, Pompe disease, acid α‐glucosidase deficiency) was identified with several biochemical genetic methods. Complementation studies in which fibroblasts from a GSD II dog were fused with fibroblasts derived from control dogs and from human patients with different clinical forms of the disease did not lead to restoration of acid α‐glucosidase activity in the heterokaryon cell populations. These results indicate that acid α‐glucosidase deficiency is the primary defect in canine GSD II and that there is a close genetic parallelism with human GSD II. Immunotitration analysis of the residual acid α‐glucosidase activity in the canine GSD II fibroblasts and liver demonstrated that this residual activity was not due to acid α‐glucosidase enzyme, in which respect canine GSD II was similar to the infantile form of the human disease. Double immunodiffusion studies showed the presence of catalytically inactive acid α‐glucosidase enzyme protein in canine GSD II. This is consistent with a structural gene mutation. It is concluded that canine GSD II in the Lapland dog is a homologous model of the infantile form of human GSD II, a conclusion in concordance with clinical and pathological studies.
Hypospadias in British Columbia
Authors: Leung T. J. , Baird P. A. , McGillivray B.
Published: June 2005

The British Columbia Health Surveillance Registry (BCHSR) records the frequency, incidence, and distribution of congenital malformations and other disabilities among individuals within the province using multiple sources of ascertainment. The most important sources of ascertainment for this study were Physician's Notice of Birth forms and discharge diagnosis from all hospitals in the province on children 7 years old or younger. These data were used to determine the minimal incidence of hypospadias with and without other congenital anomalies in order to provide information useful in management and to establish baseline prevalence data on a common genital malformation. In addition, incidence over time was evaluated.

The study found the minimal incidence of hypospadias in British Columbia to be 4.44 per 1,000 male live births (1,314 cases out of 295,656 male live births) during 1966–1981. This is in the previously reported range of the incidence of hypospadias (2–8.2 per 1,000 male live births). Hypospadias was the only malformation in almost 80% of all individuals identified.

The most frequent additional anomalies involved the genital and inguinal regions (7.2% of all cases or 36% of cases with additional anomalies). Cardiac lesions were the next most common anomalies, representing 14% of those cases with additional anomalies. Limb malformations and gastrointestinal anomalies were also quite common, representing 12.1% and 9.1% of cases of hypospadias with additional anomalies, respectively.

Thus, 1 in 225 males born in British Columbia has some degree of hypospadias, and 20% of these infants also have at least one other anomaly.
Pulmonary and diaphragmatic agenesis: Report of affected sibs
Authors: Toriello Helga V. , Higgins James V. , Jones Alan S. , Radecki Leonard L.
Published: June 2005

We report on two sibs with pulmonary and diaphragmatic agenesis, a rare combination of malformations. We conclude that this represents a previously undescribed autosomal recessive condition affecting either multiple developmental fields or a single complex polytopic field.
A family study of congenital diaphragmatic defects
Authors: Czeizel Andrew , Kovács Márta , Opitz John M. , Reynolds James F.
Published: June 2005

The occurrence of specific and nonspecific congenital anomalies was determined in first degree relatives of index patients with congenital diaphragmatic defects who were born in Hungary between 1970 and 1979 and were ascertained through a population‐based registry. The cases were grouped into Bochdalek types (N = 156), other types (N = 26), unclassified types (N = 55), and multiple congenital anomalies (MCA) cases including those with congenital diaphragmatic defects (N = 96). The sib occurrence in the Bochdalek type was 0.9% (taking into consideration also the unclassified cases or the total material, it was 0.5% or 0.4%, respectively). Specific familial clusters were not found in other types. Neural tube defects were detected in 1.8% of sibs in the total material and 2.4% in MCA cases.
X‐linked midline defects
Authors: Toriello Helga V. , Higgins James V. , Opitz John M. , Reynolds James F.
Published: June 2005

Opitz and Gilbert [Am J Med Genet 12:443–455, 1982] have postulated that the midline may be a kind of developmental field. Although developmental field defects (primary malformations) usually occur sporadically, in some instances they can be caused by a single gene mutation. We report on a family in which the occurrence of midline defects was consistent with X‐linked inheritance. Anomalies present in the family include hydrocephalus, anencephaly, cleft lip, congenital heart defect, renal agenesis, and hypospadias.
Sisters with polysplenia
Authors: De La Monte Suzanne M. , Hutchins Grover M. , Opitz John M. , Reynolds James F.
Published: June 2005

The pathogenesis of asplenia and polysplenia in humans is unknown. The conditions have been regarded as duplication of sidedness or abnormalities of embryonic curvature. The resemblance of the abnormalities in an autosomal recessive mutation (iv) in mice to those in humans with asplenia or polysplenia suggest the possibility of a genetic basis for asplenia/polysplenia in humans. We have studied a family in which two sisters had polysplenia, one sib pregnancy resulted in abortion, and two sibs and the parents are living and well with no evidence of the condition. Documentation of such families will be of value in determining the variations in expression of the condition and possible relationship between asplenia and polysplenia.
Central nervous system neoplasm in a young man with Martin‐Bell syndrome – fra(X)‐XLMR
Authors: Rodewald Lance , Miller Douglas C. , Sciorra Leonard , Barabas Gabor , Lee Ming‐liang , Opitz John M. , Reynolds James F.
Published: June 2005

A 17‐year‐old retarded male developed unilateral leg weakness with foot drop, pain, and incontinence. Workup disclosed a cauda equina tumor which, on surgical exploration, was demonstrated to merge with the conus medullaris. Pathological examination of the subtotally resected tumor led to a diagnosis of malignant ganglioglioma. Further evaluation of the patient documented marginal macro‐orchidism, and chromosome studies showed fragile X. Since some neoplasms are known to be associated with chromosomal deletions and other abnormalities, we suggest that the occurrence of this tumor in this patient indicates a more than coincidental relationship between the two diagnoses.
Autosomal suppressor gene for fragile‐X: An hypothesis
Authors: Israel Martin H. , Opitz John M. , Reynolds James F.
Published: June 2005

We suggest the existence of an autosomal suppressor gene, S, which is fairly common in the general population and acts to inhibit expression of the fra(X) gene, F. The suppression is effective in males who are hemizygous for F only if they are homozygous for S, while it is effective in females who are heterozygous for F if they are at least heterozygous for S. Thus, the fra(X) phenotype is not expressed in genotypes F‐SS, FfSS, FfSs, while it is expressed in genotypes F‐Ss, F‐ss, Ffss.

With a frequency of SS in the general population of approximately 20%, this hypothesis can explain the observed penetrance of about 80% in F‐ males and about 30% in Ff females. It can also explain the very low frequency of fra(X) expression in Ff females who are daughters or mothers of non‐penetrant F‐ males, and a lower penetrance in siblings of non‐penetrant F‐ males than in grandsons of these males. The model is in good quantitative agreement with other unique characteristics of fra(X) inheritance.
Dominant inheritance of a syndrome similar to Rubinstein‐Taybi
Authors: Cotsirilos Patricia , Taylor JoEllyn C. , Matalon Reuben , Opitz John M. , Reynolds James F.
Published: June 2005

Two sibs and their mother were affected with a syndrome like the Rubinslein‐Taybi syndrome. All three individuals had broad terminal phalanges of the thumbs and great toes, antimongoloid slant of the palpebral fissures, and characteristic facial appearance with beaked noses. Four sibs of the mother had broad thumbs, suggesting a familial pattern. So far there has been no report of dominant transmission of the Rubinstein‐Taybi syndrome. This family bears close resemblance to the Rubinstein‐Taybi syndrome, which is transmitted as an autosomal or X‐linked dominant trait. Inasmuch as the expressivity of the syndrome may be variable, we propose that a thorough family investigation is indicated in all apparently sporadic cases of Rubinstein‐Taybi syndrome. Familial cases may be more common than realized and require appropriate genetic counseling.
Dermatoglyphic traits as possible markers of developmental processes in humans
Authors: Livshits G. , Kobyliansky E. , Opitz John M. , Reynolds James F.
Published: June 2005

Here we provide data on the relationship in variability between common anthro‐pumetric characters (stature, interocular diameter, mesosternal chest circumference, bi‐trochanteric diameter, and palm length) and dermatoglyphic traits in groups of young healthy individuals.

Our working hypothesis was that quantitative variables of fluctuating asymmetry, diversity, and variability involving dermatoglyphic traits, will be higher in more homozygous groups than in heterozygous ones. It was found that individuals who were in the center (average ± 0.67 SD) of the morphological trait distribution (and therefore perhaps more heterozygous at loci determining the aforementioned morphological traits), have reduced fluctuating asymmetry in their ridge counts (RC). These heterozygous individuals tended to have lower values of the RC‐diversity‐indices and the Shanon information‐measures of discrete digital patterns.

On the basis of the present results and a large body of literature data, the use of dermatoglyphic traits as “markers” of developmental processes are discussed.
Juvenile hyaline fibromatosis: Two new patients and review of the literature
Authors: Fayad Michel N. , Yacoub Antoine , Salman Salah , Khudr Adele , Der Kaloustian Vazken M. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a sister and a brother (born to normal consanguineous parents) with joint contractures and osteolytic lesions of bones. The sister had also gingival hyperplasia and skin lesions consisting of multiple tumors of the face, nose, palate, cars, and neck. Histologic examination showed findings of juvenile hyaline fibromatosis. The literature is reviewed, and 15 cases already reported arc summarized.
Ring chromosome 6: Report of a patient and literature review
Authors: Chitayat D. , Hahm S. Y. E. , Iqbal M. A. , Nitowsky H. M. , Opitz John M. , Reynolds James F.
Published: June 2005

A patient with ring chromosome 6 had most of the manifestations previously reported in this syndrome and also had albinoid fundi and unilateral aniridia, findings not previously described. In most peripheral leukocyte metaphases analyzed, one chromosome 6 was replaced by a monocentric ring chromosome with deletion of the 6p and 6q. Fifteen other patients with a ring chromosome 6 have been reported. The most frequent findings were mental retardation, prenatal and postnatal failure, epicanthal folds, fiat nasal bridge, short neck, apparently low‐set and/or malformed ears, microphthalmia, and micrognathia. Studies of coagulation Factors XII and XIII and of the P blood group for possible assignment on distal 6p and 6q did not provide evidence for localization of the genes for these factors on the pter → p24 part of chromosome 6.
Pilodentoungulardysplasia with microcephaly: A new ectodermal dysplasia/malformation syndrome
Authors: Tajara Eloiza Helena , Pinheiro Marta , Freire‐Maia Newton , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 6‐year‐old Brazilian girl with hypotrichosis, dental alterations, onychodysplasia, microcephaly, mental retardation, precocious puberty, abnormal palmar creases, and other findings. This appears to be the first report of this multiple congenital anomalies/mental retardation (MCA/MR) syndrome which is probably due to an autosomal recessive gene.
Paternity testing 3: Exclusion probabilities
Authors: Brown Constance M. , Seber G. A. F. , Opitz John M. , Reynolds James F.
Published: June 2005

Blood typing with several blood systems is used in many countries to determine paternity or nonpaternity with respect to an alleged father. Various probabilities are usually presented, in particular: (1) the conditional probability of excluding a random man as father given a particular mother‐child phenotype combination, and (2) the expected (unconditional) exclusion probability for all mother‐child combinations can be calculated for a given blood system. Because these probabilities are of general interest in paternity studies, explicit formulae for the unconditional probabilities have been derived for some of the systems. Algorithms suitable for a microcomputer are given here for finding the exclusion probabilities for any system. These algorithms avoid the need for developing new formulae whenever a new system is introduced or a current system is extended through the addition of further alleles.
Familial situs inversus and congenital heart defects
Authors: Zlotogora J. , Schimmel M. S. , Glaser Y. , Reynolds James F.
Published: June 2005

The midline is a major determinant in the lateral symmetry of the embryo and represents a developmental field which, if defective, may lead to an abnormal situs determination. A family in which four out of seven children had situs inversus and/or congenital heart defects is presented. This report confirms the autosomal recessive inheritance of this developmental field defect.
Autosomal dominant painful plantar callosities
Authors: Rachid Acir , Freire‐Maia N. , Pinheiro Marta , Opitz John M. , Reynolds James F.
Published: June 2005

We describe large kindred with an autosomal dominant condition characterized by painful callosities that develop over the pressure points of the soles. These callosities are not congenital; they arise with upright ambulation.
Autosomal dominant cerebro‐costo‐mandibular syndrome: Ultrasonographic and clinical findings
Authors: Merlob Paul , Schonfeld Alex , Grunebaum Michael , Mor Naomi , Reisner Salomon H. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe two patients, a father and his daughter, with the cerebro‐costo‐mandibular syndrome. New manifestations not previously described include mi‐crostomia, long philtrum, posterior cervical skin fold, short internipple distance, and depressed sacral region. The presence of hydrocephaly in the proposita and spina bifida in the father may be other manifestations of neuraxial involvement in this syndrome. The first intrauterine ultrasonographic documentation of this syn‐drome showed polyhydramnios and, especially, the very unusual shape of the ribs, which were short and defective. Most characteristics of the pedigree point to autosomal dominant inheritance. The great variability of inheritance and expres‐sivity of the very few documented familial cases described in the literature, together with the great frequency of sporadic cases, indicates genetic heterogeneity of this syndrome.
Partial duplication 16p resulting from a 3:1 segregation of a maternal reciprocal translocation
Authors: Mori Maria A. , Gomar Juan L. , de Bustamante Aranzazu Diaz , Ananias Abraham , Pinel Ismael , Martinez‐Frias Maria L. , Reynolds James F.
Published: June 2005

We report on a male infant with a duplication 9p (pter → q13) and duplication 16p (p13 → pter) resulting from a 3:1 meiotic disjunction of a maternal reciprocal translocation. In this case, the mode of segregation fits to the Pachytene‐Diagram Model of Jalbert el al [1980]. The infant showed clinical features that have been described both in dup(16p) and in dup(9p). To our knowledge, this is the first time that this unbalanced karyotype has been reported.
Presymptomatic testing for Huntington chorea: Guidelines for moral and social accountability
Authors: Smurl James F. , Weaver David D. , Opitz John M. , Reynolds James F.
Published: June 2005

Clinical trials of a presymptomatic test for Huntington chorea (HC) are beginning, and the test may set precedents in screening for other genetic disorders in this way. Therefore, it seems an opportune time to consider the moral and social implications of such testing. The strategy proposed here takes the form of guidelines for research, development, and clinical application of the HC test and any future similar tests. The guidelines cover four stages (preliminary research, verification, refinement, and clinical application). They draw on past experience, on existing guidelines for research involving human subjects, and on some ueneral moral and legal principles. In addition to traditional concerns about relationships between counselors and consultands, they emphasize more contemporary concerns about the interests of third parties and social institutions in what occurs in modern methods of genetic screening. In all cases, however, the guidelines are provisional and are offered here mainly for purposes of discussion and to encourage similar efforts at policymaking by those who become involved with these forms of testing.
Attitudes of persons at risk for Huntington disease toward predictive testing
Authors: Kessler Seymour , Field Tracy , Worth Laura , Mosbarger Heidi , Opitz John M. , Reynolds James F.
Published: June 2005

Attitudes of 69 persons at risk for Huntington disease (HD) were obtained by means of semistructured interviews and questionnaires. About 79% of the individuals said that they would use a presymptornatic predictive test if it were available. All believed that the test should be made available even though there was no cure for HD. Nearly 2/3 of subjects would use the test for prenatal diagnosis, and of these 71% would terminate a pregnancy if the fetus was found to carry the HD gene. Most subjects believed that pretest counseling should be mandatory and many said that testing should be withheld from persons who were psychologically unstable or were threatening self‐harm. The data suggest that about 2–6% of persons at risk for HD may have severe psychiatric or suicidal responses to a positive outcome of predictive testing. This underscores the need for adequate pretest counseling and the availability of professional and community resources tó deal with the impact of predictive testing on individuals and their relatives.
Attitudes toward presymptomatic testing in Huntington disease
Authors: Mastromauro Carol , Myers Richard H. , Berkman Barbara , Opitz John M. , Reynolds James F.
Published: June 2005

One hundred thirty‐one individuals at 50% risk of inheriting Huntington disease (HD) responded to a survey to study their attitudes toward taking a genetic test based on the identification of a genetically linked DNA polymorphism. Ninety‐six percent of the respondents believe that presymptomatic testing should be available, and 66% say they will use it themselves. Fewer married individuals, in comparison to those single, separated, and divorced, intend to take the test. Many respondents (40%) said their primary reason for wanting to be tested is to end the uncertainty in their lives. Results suggest that there will be self‐selection in test use, with many individuals who believe they will be depressed or possibly suicidal with a positive test result deciding not to be tested or unsure about testing. However, 15% of those who want to be tested acknowledge that they may be at risk for suicide if they are probable gene carriers. Only 12% of all respondents say they will be likely to use prenatal testing, suggesting that initial demand may be low in New England. Implementation of presymptomatic testing challenges health care providers to develop strategies to care for otherwise healthy persons who will be given a diagnosis years before the onset of illness.
At‐risk Persons' attitudes toward presymptomatic and prenatal testing of Huntington disease in Michigan
Authors: Markel Dorene S. , Young Anne B. , Penney John B. , Opitz John M. , Reynolds James F.
Published: June 2005

One hundred fifty‐five individuals at 50% risk of inheriting Huntington disease (HD) were given a questionnaire surveying their sociodemographic characteris‐tics, experience with HD, and attitudes toward presymptomatic and prenatal testing in HD. About two‐thirds (63.2%) of the persons indicated they would take a presymptomatic test even if no specific treatment was available. Although one‐half (49%) of the respondents stated they would make use of a prenatal test, only 43% of these individuals would decide to terminate a heterozygous fetus. Presym‐patomatic test results indicating carrier status would influence some of the respondents' decisions about marriage and childbearing. This strong interest of at‐risk persons to make use of both presymptomatic and prenatal diagnosis in HD indicates the need for well‐organized testing programs. These programs must be designed to address the genetic, psychosocial, and ethical issues that may arise in the use of this type of genetic test.
Congenital corneal anesthesia with retinal abnormalities, deafness, unusual facies, persistent ductus arteriosus, and mental retardation: A new syndrome?
Authors: Ramos‐Arroyo Maria A. , Clark G. Gregory , Saksena Sudha S. , Modes M. E. , Opitz John M. , Reynolds James F.
Published: June 2005

Two sibs who had hypesthetic corneas, absence of the peripapillary choriocapillaris and retinal pigment epithelium, sensorineural hearing loss bilaterally, persistent ductus arteriosus, moderate mental retardation, and unusual facial appearance are described. Their mother had mild to moderate sensorineural hearing loss, retinal changes and similar facial features. The differential diagnosis is discussed. We believe this is a clinically distinct syndrome with autosomal dominant inheritance.
Autosomal recessive nonsyndromal microcephaly with normal intelligence
Authors: Teebi Ahmad S. , Al‐Awadi Sadika A. , White Arthur G. , Reynolds James F.
Published: June 2005

Autosomal recessive microcephaly is usually associated with moderate to severe mental retardation. An apparently new autosomal recessive disorder comprising a characteristic facial appearance associated with microcephaly and normal intelligence, immunodeficiency, and increased risk for lymphoreticular malignancies has been described recently. We report on a large Arab kindred with frequent consanguineous marriages and eight cases in five sibships with microcephaly, peculiar facies, and normal intelligence. Of these cases, two died of an acute lymphoreticular malignancy or bronchopneumonia. Immunological and chromosomal studies carried out for the three affected living sibs were normal. The existence of an autosomal recessive nonsyndromal variant of microcephaly with normal intelligence is proposed and discussed.
Oculoauriculovertebral dysplasia and variants: Phenotypic characteristics of 294 patients
Authors: Rollnick Beverly R. , Kaye Celia I. , Nagatoshi Konrad , Hauck Walter , Martin Alice O. , Reynolds James F.
Published: June 2005

Here we describe the phenotypic characteristics of a single craniofacial clinic population of 294 individuals affected with Oculoauriculovertebral dysplasia (OAV) and variants. To our knowledge, this is the largest population so described in the literature.

The study population was divided into five subgroups based on the presence of combinations of minimal diagnostic criteria: microtia, mandibular hypoplasia, anomalies of the cervical spine and/or epibulbar or lipodermoids. The following data were recorded: (1) sex (M:F 191:103); (2) race (78% Caucasian); (3) the presence of unilateral or bilateral microtia (193 unilateral, 98 bilateral); (4) the presence of symmetric microtia in bilateral cases (34/98); (5) the presence of mandibular hypoplasia ipsilateral or contralateral to the microtic ear or most severely microtic ear in bilateral cases (135/137 were ipsilateral in unilateral cases, 55/62 were ipsilateral in bilateral cases); (6) the number of individuals with no Other congenital anomaly in addition to the minimal diagnostic criteria (154/294), with only one other congenital anomaly (51/294), and with two or more other congenital anomalies (89/294); and 7) the type of other congenital anomalies. Finally, we compared our results with other studies.

Findings from our study include: (1) mandibular asymmetry should be expected in patients with unilateral or bilateral microtial; (2) bilateral involvement is frequent in patients with microtia; (3) other malformations are seen frequently in all subgroups; (4) anomalies of the cervical spine are more likely to be associated with other anomalies; and (5) other malformations are seen in all systems and should be searched for to provide optimal management.
Vitamin B12 responsive homocystinuria and megaloblastic anemia: Heterogeneity in methylcobalamin deficiency
Authors: Rosenblatt D. S. , Thomas I. T. , Watkins D. , Cooper B. A. , Erbe R. W. , Reynolds James F.
Published: June 2005

A male infant with methyl‐B12 deficiency (cblE) presented at age 6 weeks with lethargy, staring spells, and vomiting. He later became hypotonic and unrespon sive to stimuli and required intubation and ventilation. He had homocystinuria and hypomethioninemia with megaloblastic anemia but normal serum folate and vitamin B12 concentrations. No methylmalonic aciduria was detected. Fibroblasts, cultured from the patient, were unable to grow in medium in which homocysteine replaced methionine and incorporated abnormally small amounts of [14C]‐methyl‐tetrahydrofolate but normal amounts of [14C]‐propionate into protein. Methyl‐B12 content of fibroblasts was low, while the adenosyl‐B12 content was normal. Methionine synthase activity was decreased when the assay was performed under both optimal and suboptimal reducing conditions, suggesting heterogeneity in the cblE disease. The patient responded dramatically to hydroxocobalamin treatment. Homocystinuria disappeared after 10 days of therapy, and methionine was normalized after 3 weeks. Psychometric testing at age 15 months showed a developmental age of 9 months.
Menkes syndrome in a girl with X‐autosome translocation
Authors: Kapur Saroj , Higgins James V. , Delp Kathleen , Rogers Brian , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a girl with Menkes syndrome (M.S.) and X‐2 reciprocal translocation. We conclude that the probable locus for M.S. gene is at band Xql3. This case and other previous case reports of X‐linked disorders in females suggest that chromosome analysis is indicated in all females who present with manifestations of a known X‐linked lethal condition in order to detect a possible associated balanced X‐autosome translocation.
Consumer costs for genetic services
Authors: Myers Terry L. , Prouty Leonard A. , Opitz John M. , Reynolds James F.
Published: June 2005

Since the mid‐1970's, inflation and changing patterns of subsidies for genetic service centers in the United States have increased the costs of these services for patients and insurers. We have monitored this trend by periodically surveying the providers of these services to determine their current billing rates. We report here recent rates for cytogenetic laboratory services as well as for clinical in‐ and outpatient genetic consultations. Prices for the main laboratory and consultation services are approximately twice their 1976 level, but these increases parallel those of medical care. The inflationary trend is slowing. Geographic variations in pricing differences in charges between M.D.'s and Ph.D.'s, and certain personnel trends in genetic centers are apparent in our data.
Metaphase chromosome folds and X‐inactivation
Authors: Butler Merlin G. , Joseph Geeta M. , Dev V. G. , Reynolds James F.
Published: June 2005

To evaluate the suggested nonrandom folding of Xql3‐q21 (center of Barr body condensation) of the inactivated X chromosomes, metaphases from nine subjects with or without X chromosome abnormalities (eight females and one male) were investigated with RBG‐staining. A significant increase (p < .05) in the number of arm folds (Xq13‐q21) of the late‐replicating X chromosome, particularly in early to mid‐metaphase, was observed in four of eight females. Therefore, the stage of chromosome contraction was an important factor with more folds observed at the centromeres and in longer chromosomes in early metaphase compared with mid‐ to late metaphase. X chromosome folds were present in cells of subjects treated with or without bromodeoxyuridine. While our study agrees with the relationship of Xql3‐q21 fold with the X‐inactivation center, the correlation of extended chromosomes and folding limits this method as a sole indicator of X‐inactivation in routine mid‐metaphase, but is useful in the analysis of early metaphase chromosomes.
Familial CHARGE syndrome: Clinical report with autopsy findings
Authors: Metlay Leon A. , Smythe Peter S. , Miller Marvin E. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a patient with CHARGE syndrome, as manifested by a coloboma of the optic nerve head, congenital heart defect (ASD, VSD, and parachute mitral valve), choanal atresia, severe growth retardation, genital hypoplasia, abnormal ears, cleft lip and palate, and pectus carinatum. His chromosomes were normal. He died at 19 months. His mother was short and had hearing impairment, choanal atresia, and a coloboma. We suggest that this represents evidence for dominant transmission of this disorder in this family. Other familial cases from the literature are reviewed.
Sedaghatian congenital lethal metaphyseal chondrodysplasia—observations in a second Iranian family and histopathological studies
Authors: Opitz John M. , Spranger Jürgen W. , Stöss Hartmut R. , Pesch Hans‐Jürgen , Azadeh B. , Reynolds James F.
Published: June 2005

In 1980, Sedaghatian described in two brothers and one sister a neonatally lethal disorder associated with slight rhizomelic limb shortness, mild platyspondyly, and severe metaphyseal dysplasia. Here data are presented on another Iranian infant with the Sedaghatian syndrome who died on day 4 and was found to have histologic evidence of severe epimetaphyseal dysplasia. The occurrence in chil‐dren of both sexes in one instance, born to normal parents who were first cousins, and currently apparent confinement of the disorder to Iranians suggests that the Sedaghatian syndrome is an autosomal recessive trait with high gene frequency in Iranians. This may be a more complexly pleiotropic syndrome than suggested by the roentgenograms, since one of Secaghatian's patients also had “microphthal‐mia, asymmetry of ears, depressed nasal bridge, broad nose, short neck, promi nent sternum, and short lower extremities”.
Reproductive choices in hemophilic men and carriers
Authors: Miller Connie H. , Hilgartner Margaret W. , Aledort Louis M. , Opitz John M. , Reynolds James F.
Published: June 2005

We have examined reproduction patterns in hemophilic men and carrier women seen at a hemophilia treatment center. The study group included 309 patients with hemophilia A or B: 194 adults and 115 children from 246 pedigrees; 93% of affected men and 96% of parents of affected children had received genetic counseling. In the collected pedigrees, 65 % of affected males were born to women with family history of hemophilia. An additional 23% of mothers were later shown to be carriers. Fewer than 12% of cases could be due to a new mutation in the child. Among 209 hemophilia A carrier tests, 95% of obligate carriers were detectable, 87% of mothers of sporadic cases, 53% of sisters of hemophiliacs, and 24% of other relatives had a high risk of carriership. Of 49 high‐risk women seen during or prior to pregnancy, one‐half elected prenatal diagnosis. Amniocen‐tesis was performed in 24 cases and 8 were referred for fetoscopy, resulting in 18, normal offspring. Among 25 pregnancies not tested, 14 continued and produced 3 affected males and 11 normal offspring. Of hemophilic men over age 25, 66% have married and 41% (62% of those married) have had children. These obser‐vations will serve as a baseline for assessing any change in reproductive patterns occurring with the introduction of new genetic techniques.
New marfanoid syndrome with craniosynostosis
Authors: Furlong Judith , Kurczynski Thaddeus W. , Hennessy James R. , Reynolds James F.
Published: June 2005

We report on a patient with various connective tissue abnormalities suggesting a distinctive disorder combining some features of the Marfan syndrome with cranio‐synostosis and other anomalies. A comparison is made with the Marfan syndrome and other phenotypically similar conditions.
Male excess among anatomically normal fetuses in spontaneous abortions
Authors: Byrne Julianne , Warburton Dorothy , Opitz John M. , Reynolds James F.
Published: June 2005

Estimates of the sex ratio in miscarriages, obtained mainly by cytogenetic or nuclear sexing methods, have yielded conflicting results. We report the results of a study of the anatomic sex ratio among embryos and fetuses derived from a consecutive series of 3,469 miscarriages. The overall sex ratio (M:F) was 1.25. The male excess was confined to normally formed specimens (1.30) and was present at all gestational ages up to 23 weeks and all sizes over 5 cm. Among malformed specimens the sex ratio was close to unity (0.92). Agreement between chromosomal and anatomic sexing was excellent, and the cytogenetic sex ratio among anatomically normal abortuses showed a similar excess of males. We hypothesize that an excess of anatomic males among fetal deaths suggests the presence of a discrete cause or causes that operate on normally formed embryos and fetuses, whereas loss of malformed embryos and fetuses may be due to other mechanisms that affect females as often as males.
Vertical transmission of the neurofibromatosis/Noonan syndrome
Authors: Quattrin Teresa , McPherson Elspeth , Putnam Theodore , Opitz John M. , Reynolds James F.
Published: June 2005

We are reporting on a boy and his mother with neurofibromatosis and manifestations of Noonan syndrome, including short stature, ptosis, midface hypoplasia, and short neck. Developmental delay was noted in the son, and the mother was noted to have a heart murmur. There was a family history of café‐au‐lait spots, and photographs of several of these relatives showed a facial appearance suggesting Noonan syndrome. The presence of neurofibromatosis associated with Noonan syndrome manifestations in our related patients suggests presence of a unique disorder sharing characteristics of both conditions.
Neural tube defects and sex ratios
Authors: Seller Mary J. , Opitz John M. , Reynolds James F.
Published: June 2005

The sex ratio of 147 fetuses with presumed multifactorial neural tube defect (NTD) was studied. Overall, the ratio (males:females) was 0.73 with expected female excess. However, when the NTDs were subdivided according to the site of the lesion, the sex ratios varied. Total craniorachischisis, anencephaly with cervical spina bifida, holoacrania, and thoracic spina bifida showed a greater female excess than that overall; the sex ratio for meroacrania was close to unity, while that for low spinal lesions, particularly those involving the sacrum, showed an extreme bias towards males. These findings are related to the mode of formation of the neural tube. Females seem prone to defects of neurulation and males to defects in canalisation. An explanation for these findings is suggested in possible sex differences in rate of early embryonic development.
H‐Y typing by ELISA in a 46,X,dic(Y)(q11.2101) male: Effects of a nonmosaic Yp duplication
Authors: Moreira‐Filho Carlos A. , Wachtel Stephen S. , Daniel Art , Priest Jean H. , Opitz John M. , Reynolds James F.
Published: June 2005

A new ELISA was used to measure H‐Y antigen in cultured fibroblasts from a male with 46,X,dic(Y)(qll.2101) involving duplication of Yp. Aliquots of mono‐clonal H‐Y antibody were absorbed with 1, 2, 4, or 8 × 106 cells from the 46,X,dic(Y) male, or with corresponding numbers of cells from a normal XY male and a normal XX female, and then were tested for residual activity against a soluble antigen source. Portions of the antibody absorbed with cells of the 46,X,dic(Y) male were found to be less reactive than portions absorbed with cells of the normal XY male, for all numbers of cells and both dilutions of plated antigen. The results, quantified in an electronic optical density reader, imply presence of excessive H‐Y in cells of the 46,X,dic(Y) male, and suggest presence of a genetic determinant of H‐Y on Yp or proximal Yq near the centromere.
Duplication of distal 15q: Report of five new cases from two different translocation kindreds
Authors: Lacro Ronald V. , Jones Kenneth Lyons , Mascarello J. T. , Jones Oliver W. , Wilson Nevin , Jones Marilyn C. , Reynolds James F.
Published: June 2005

Four children and one spontaneously aborted fetus from 2 separate families have a similar pattern of malformation secondary to duplication of distal 15q. In both families, the abnormal chromosomes were derived from balanced reciprocal translocations carried by the mothers. Clinical features common to the 4 liveborn children include appropriate birth weight, length, and head circumference for gestational age; similar craniofacial anomalies, including sloping forehead, bulbous nose, prominent nasal bridge and septum, midline crease in the lower lip, and micrognathia; arachnodactyly; joint contractures involving hands and feet; cardiac defects; and genital anomalies. The 2 infants with duplication 15q22.1‐ → qter and deletion 13q32.3‐ → qter died in the immediate neonatal period. The abortus, who shared the same chromosome constitution, had an omphalocele and a cephalic defect in neural tube closure. The 2 children with duplication 15q22‐ → qter and deletion 11q25‐ → qter survived but have severe psychomotor retardation and postnatal onset growth deficiency, at 48 and 30 months, respectively. The findings in these 5 cases plus review of the literature permit further delineation of a recognizable pattern of malformation secondary to duplication of distal 15q.
Studies in neural tube defects I. Epidemiologic and etiologic aspects
Authors: Myrianthopoulos Ntinos C. , Melnick Michael , Opitz John M. , Reynolds James F.
Published: June 2005

In the NIH Collaborative Perinatal Project, a prospective study of over 53,000 pregnant women and their offspring, 71 single‐born children (13.33/10,000) were found to have a non‐syndromal neural tube defect (NTD). A family history was present in only one case. The group of individuals with NTD was compared to a group of 400 randomly selected non‐malformed control infants. Of over 50 maternal factors studied the following showed significant association with NTD in the offspring: diabetes mellitus; organic heart disease; lung disease; and diuretic, antihistamine, and sulfonamide use. The interval between the termination of the immediately previous pregnancy and the start of the proband pregnancy was significantly shorter in mothers of NTD children than in mothers of control infants. The risk for NTD was also significantly increased if the immediately previous pregnancy was a spontaneous abortion. There was no increased risk for NTDs among sibs of children with major malformations such as tracheo‐esopha‐geal “dysraphism,” cleft lip/palate, or renal agenesis. NTDs are apparently etiologically heterogeneous.
Studies in neural tube defects II. Pathologic findings in a prospectively collected series of anencephalics
Authors: Melnick Michael , Myrianthopoulos Ntinos C. , Opitz John M. , Reynolds James F.
Published: June 2005

This report presents the pathologic anatomy of a prospectively collected series of 36 anencephalic infants. This series provides an opportunity to investigate the epidemiology of organ system pathology in anencephaly (AN) as well as other facets of its natural history. AN infants had a mean gestational age 2.5 weeks younger than normal controls, though birthweight was normal for gestational age. Nearly 1/3 of the liveborn infants with AN died within 15 minutes, 2/3 within 3 hours; 3 AN infants survived to 48 hours. Details and discussions of the pathologic findings and their physiologic significance are presented. Regarding those AN infants who received detailed neurologic examinations, correlations are made between the brain pathology and neurologic function prior to death.
A new case of the osteodysplastic primordial dwarfism type II
Authors: Willems Patrick J. , Rouwé Catrienus , Smit G. Peter A. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a girl with extreme growth retardation of prenatal onset, short limbs, and somewhat unusual facial appearance. She represents the 6th patient with osteodysplastic primordial dwarfism type II. The distant consanguinity of the parents of this patient suggests possible autosomal recessive inheritance.
A syndrome of microcephaly, eye anomalies, short stature, and mental deficiency
Authors: Bavinck Jan N. Bouwes , Weaver David D. , Ellis Forrest D. , Ward Richard E. , Opitz John M. , Reynolds James F.
Published: June 2005

We have studied a mother and son with a previously apparently undescribed syndrome of microcephaly, eye defects, small ears, mild mental deficiency, and short stature. The syndrome appears to be an autosomal or X‐linked dominant trait. The cat eye syndrome, blepharophimosis or Kohn‐Romano syndrome, Rieger syndrome, and other disorders are discussed in relationship to this entity.
Phenotype heterogeneity among hemizygotes in a family biochemically screened for adrenoleukodystrophy
Authors: Cotrufo R. , Melone M. A. B. , Monsurro M. R. , Di Iorio G. , Carella C. , Moser H. W. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on two clinically, neurologically normal relatives of a boy affected by adrenoleukodystrophy (ALD); they were found repeatedly to have the biochemical defect of an ALD hemizygote. The assay consisted in the determination of very‐long‐chain fatty acids in lyophilized and reconstituted plasma.

While no evidence of neurologic disease (leukodystrophy or myeloneuropathy) was present in these hemizygotes, adrenocortical insufficiency provoking compensatory high ACTH release was found in both. These findings should be taken into consideration when counseling families in which cases with clinically expressed ALD are represented in several generations.
Idiopathic multicentric osteolysis with facial anomalies and nephropathy
Authors: Carnevale Alessandra , Canún Sonia , Mendoza Luciano , del Castillo Victoria , Reynolds James F.
Published: June 2005

Idiopathic osteolysis denotes a group of ran; bone disorders differentiated on the basis of clinical, radiological, and geneti; criteria. Idiopathic multiccniric ostco‐lysis (IMO) is one form of osteoiysis that can occur as an autosomal dominant condition.

In childhood, affected individuals have arthritic‐like episodes, followed by progressive deformities, radiological osteolytic changes, and variable degrees of disability. A peculiar face and variable renal involvement have been described as associated manifestations.

We report on a family with three members affected by IMO in two generations showing variable bone changes and persistent proteinuria. A sporadic case with severe renal damage is also described in which a de novo dominant mutation is suggested.

All patients had peculiar facial manifestations including triangular shape, protruding eyes, and micrognathia. These manifestations may be part of the syndrome of IMO.
Familial congenital funnel chest
Authors: Leung Alexander K. C. , Hoo Joe J. , Reynolds James F.
Published: June 2005

We observed three Chinese families in which congenital isolated funnel chest was segregating. This report confirms that funnel chest (pectus excavatum) can be transmitted as an autosomal dominant trait.