bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of serum hexosaminidase for the presumptive diagnosis of type I Gaucher disease in Tay‐Sachs carrier screening
Authors: Nakagawa Sachiko , Kumin Selma , Sachs Gay , Nitowsky Harold M.
Published: June 2005

Although reduced acid β‐glucosidase activity appears to be the primary enzyme defect in type I Gaucher disease, patients with this disorder also have marked elevation of serum acid phosphatase and β‐hexosaminidase activities but with a normal level of lactic dehydrogenase activity. Moreover, there is a characteristic alteration in the hexosaminidase isozyme distribution with a striking increase in hexosaminidase B. Since these changes appear to be consistent and unlike those associated with other disorders or the hormonally induced alterations associated with pregnancy, routine serum testing for the Tay‐Sachs carrier state may offer a useful approach for the presumptive diagnosis and screening for Gaucher disease. Unlike the changes in affected homozygotes, there are no characterisitic alterations of acid phosphatase or hexosaminidase in heterozygotes for Gaucher disease.
Ullrich‐turner syndrome associated with interstitial deletion of Xp11.4→p22.31
Authors: Wilson Miriam G. , Modebe O. , Towner Joseph W. , Frasier S. Douglas , Lin Ming S. , Opitz John M.
Published: June 2005

The full phenotype of the Ullrich‐Turner syndrome (UTS) is thought to be due to loss of the short arm of X. We report a 16‐year‐old girl with lack of secondary sexual development, amenorrhea, and short stature. She had thyroiditis and numerous other UTS manifestations and was found to have a non‐mosaic 46,X,del(Xp) chromosome abnormality. Breakpoints occurred at p11.4 and p22.31, with a loss of the intervening segment.
Autosomal recessive anophthalmia with multiple congenital abnormalities—type Waardenburg
Authors: Richieri‐Costa A. , Gollop T. R. , Otto P. G. , Opitz John M.
Published: June 2005

We report two Brazilian families with children who had anophthalmia and multiple congenital abnormalities and consanguineous parents. Among the five affected children, four had bilateral and one had unilateral anophthalmia. Autosomal recessive inheritance is demonstrated.
The branchio‐oto‐renal (BOR) syndrome: Report of bilateral renal agenesis in three sibs
Authors: Carmi R. , Binshtock M. , Abeliovich D. , Bar‐Ziv J. , Opitz John M.
Published: June 2005

We report a man who had the branchio‐oto‐renal (BOR) syndrome with crossed renal ectopia. His three children were born with bilateral renal agenesis and the so‐called Potter syndrome.

This case illustrates the potential severity of the renal anomalies in the BOR syndrome and the inadequacy of oligohydramnios and maternal serum alpha‐fetoprotein as screening methods for renal agenesis. This case also implies strongly the necessity for meticulous search for renal anomalies in individuals with the BOR syndrome and proper counseling regarding the possiblity of lethal bilateral renal agenesis.
Familial paracentric inversion of 1p
Authors: Romain Dennis R. , Columbano‐Green Letizia M. , Whyte Sally , Smythe Rosalind H. , Parfitt Richard G. , Gebbie Owen B. , Chapman Cyril J. , Opitz John M.
Published: June 2005

We report a paracentric inversion of 1p in a boy with mild mental retardation. The chromosome aberration was identified by high resolution chromosome banding, and was also present in his phenotypically normal mother and other relatives. The boy's karyotype was considered to be 46,XY,inv(1) (p31,2 p36.22) ISCN (1981).
Duplication 8q syndrome due to familial chromosome ins(10;8)(q21;q212q22)
Authors: Bowen P. , Fitzgerald P. H. , Gardner R. J. M. , Biederman B. , Veale A. M. O.
Published: June 2005

We describe a kindred in which an ins(10;8)(q21;q212q22) chromosome rearrangement has been segregating for at least four generations. The risk for balanced carriers to have offspring with duplication of 8q212→8q22 is about 0.31. Individuals with unbalanced chromosomes are mildly to moderately mentally retarded and have a similar unusual appearance. Other manifestations include highly arched or cleft palate (8/9), micrognathia (6/9), sloped shoulders (4–6/9), convulsions (4/9), camptodactyly (3/9), pectus excavatum (2/9), elbow contractures (1/9), and postaxial polydactyly (1/9). The appearance and habitus resemble the mosaic trisomy 8 syndrome, although other anomalies of mosaic trisomy 8, such as vertebral, patellar, and renal defects, were not demonstrated.
Clinical and genetic aspects of antithrombin III deficiency
Authors: Halal Fahed , Quenneville Guy , Laurin Suzanne , Loulou Ginette , Opitz John M.
Published: June 2005

We have reviewed the clinical data on 120 individuals (from four personally studied families and 14 families from the literature) with inherited symptomatic antithrombin III deficiency in order to obtain information useful for genetic counseling and short‐ and long‐term prophylaxis in heterozygotes of the mutant gene.
HARD (± E) syndrome: Report of a sixth family with support for autosomal‐recessive inheritance
Authors: Aymé Ségolène , Mattei Jean‐François
Published: June 2005

We report on two sibs with hydrocephalus, encephalocele, agyria and ocular anomalies, an association known as the HARD ± E syndrome. This is thought to be the sixth reported family and third instance of familial occurrence of this autosomal‐recessive syndrome which deserves consideration in the nosology of every case of neural tube defect (hydrocephalus).
Autosomal dominant partial lipodystrophy associated with Rieger anomaly, short stature, and insulinopenic diabetes
Authors: Aarskog Dagfinn , Ose Leiv , Pande Helene , Eide Nils , Opitz John M.
Published: June 2005

We describe the clinical findings and natural history of an autosomal dominant form of partial lipodystrophy found in four affected individuals from three generations in the same family. The lipodystrophy was present from infancy/early childhood, involved primarily the face and local areas on the buttocks, and was nonprogressive. Affected individuals also had the Rieger anomaly, midface hypoplasia, short stature, retarded bone age, and hypotrichosis. An affected woman developed insulinopenic diabetes mellitus at 39 yr and another had glucose intolerance at 55 yr.
Oculogastrointestinal muscular dystrophy
Authors: Ionasescu Victor , Opitz John M.
Published: June 2005

The author reports on four patients (one male, three females) from the same kindred with a newly recognized autosomal recessive condition involving striated and smooth muscle that has been designated oculogastrointestinal muscular dystrophy. It is characterized by ptosis, ophthalmoplegia, and progressive intestinal pseudo‐obstruction leading to malnutrition and death before 30 y. Autopsy studies in two cases showed a severe primary myopathy of smooth muscles of the stomach and intestine with intact myenteric plexus and vagus nerves. The proposita notably had myopathic changes of striated muscles but also involvement of the peripheral nerves and central nervous system characterized by demyelinating and axonal neuropathy and focal spongiform degeneration of the posterior columns.
Brief report: Linkage between G6PD and fragile‐X syndrome
Authors: Filippi Giorgio , Rinaldi Antoniettina , Archidiacono Nicoletta , Rocchi Mariano , Balazs Ivan , Siniscalco Marcello
Published: June 2005

Eighteen Sardinian pedigrees segregating for the X‐fragile site syndrome were studied with respect to the segregation of the fragile site (FS) at Xq28, mental retardation, and macro‐orchidism. No exception was found in the association of this symptomatic triad (MOM‐X) in 41 out of 42 patients examined. The exceptional individual had micro‐ rather than macro‐orchidism and was found to have a 47, XXY sex chromosome complement. In six informative sibships, the MOM‐X syndrome was found to segregate in close linkage association with G6PD‐deficiency or protan colorblindness. The maximum likelihood estimate of recombination is 6% with 90% fiducial limits between 2.5 and 19.5% and an odds ratio in favor of measurable linkage of 428:1. However, no hint of measurable linkage was found in six pedigrees segregating for G6PD and the Renpenning syndrome or other unspecified types of X‐linked mental retardation. These data give strong support to the generally held hypothesis that the FS at Xq28, characteristic of the MOM‐X syndrome, is a direct expression of a genetic change in the same chromosomal region. They also clearly suggest that X‐linked MR without FS may be the result of different allelic mutations at the same locus.
Interstitial deletion 2q31→q33
Authors: Buchanan Philip D. , Rhodes Robin L. , Stevenson C. Edward , Opitz John M.
Published: June 2005

We present an 8‐month‐old female with severe retardation of growth and development, multiple congenital anomalies, and an interstitial deletion del(2)(q31→q33) including results of cytogenetic and gene marker studies. The manifestations of this infant are compared with those of four other known patients with a partial del(2q).
Dominantly inherited syndrome of microcephaly and cleft palate
Authors: Halal Fahed , Opitz John M.
Published: June 2005

Two sisters and their mother had a syndrome of microcephaly, cleft palate, and variable anomalies such as unusual facial appearance, hypotelorism, abnormal retinal pigmentation, maxillary hypoplasia, goiter, camptodactyly, mild mental retardation, and abnormal dermatoglyphics. This is an evidently dominantly inherited trait, either autosomal or X‐linked.
Chondroectodermal dysplasia (Ellis‐van Creveld) with anomalies of CNS and urinary tract
Authors: Rosemberg Sérgio , Carneiro Paulo C. , Zerbini Maria Claudia N. , Gonzalez Claudette H. , Opitz John M.
Published: June 2005

We report on a 19‐month‐old girl with chondroectodermal dysplasia (Ellis‐van Creveld) and other previously undescribed visceral and central nervous system anomalies. These anomalies include cerebral heterotopias, renal agenesis, and congenital megaureter.
Presence of H‐Y antigen in female patients with sex‐chromosome mosaics and absence of testicular tissue
Authors: Müller Ulrich , Mayerova Antonia , Fraccaro Marco , Zuffardi Orsetta , Mikkelsen Margareta , Prader Andrea
Published: June 2005

H‐Y antigen was tested in five women with sex chromosome mosaicism and gonadal streaks. Three patients had a 45,X/46,XY or 46,X,der(Y) and two a 45,X/46,X,der(X) chromosome constitution. All patients were H‐Y antigen positive. Lack of testis differentiation in these women may be explained by subthreshold expression of H‐Y antigen, different H‐Y antigen molecules, and/or different tissue distribution of the chromosome mosaicism.
Postzygotic D/D translocation homozygosity associated with recurrent abortions
Authors: Maeda Tohru , Ohno Michiko , Takada Masumi , Matsunobu Akira , Arai Masao
Published: June 2005

A Robertsonian translocation involving homologous D chromosomes was found in two cases with a history of recurrent abortions. In the first case the propositus was a 37‐year‐old phenotypically normal man who had a balanced t(14q14q) translocation. In the second case, a 27‐year‐old phenotypically normal woman was found to be a balanced t(15q15q) translocation carrier. The recurrent abortions in both cases were probably owing to this translocation.
Consanguinity studies in Wisconsin I: Secular trends in consanguineous marriage, 1843–1981
Authors: Lebel Robert Roger , Opitz John M.
Published: June 2005

Over 920,000 Roman Catholic marriages have taken place since the Archdiocese of Milwaukee was established in 1843. Most of these records are extant, and all have been examined to ascertain consanguineous marriages. The changing average population coefficient of consanguinity has been calculated, by year and by decade, showing a clear downward trend since the turn of the century. The data are compared with reports of consanguineous marriage incidence from around the world, and in particular with all available previous reports from the United States.
Study of nucleolar organizer in women with galactorrhea, or polycystic ovaries, or using oral contraceptive
Authors: Li Xinzhi , Zhou Xianting , Opitz John M.
Published: June 2005

In this paper we report on changes of the Ag‐stained NOR (Ag‐NOR) and Ag‐stained acrocentric association (Ag‐AA) frequencies in lymphocytes of women with polycystic ovaries, galactorrhea, or taking oral contraceptives. The results showed that Ag‐AA frequencies were increased significantly in all three study groups while the Ag‐NOR frequencies apparently did not increase.

We assume that a difference in average Ag‐NOR frequency between the two groups may be a measure of the change in the number of active rRNA genes, and that differences of Ag‐AA frequency among populations reflect the change in transcriptional rate of the active rRNA genes.
Part II. Amyoplasia: Twinning in amyoplasia—a specific type of arthrogryposis with an apparent excess of discordantly affected identical twins
Authors: Hall J. G. , Reed S. D. , McGillivray B. C. , Herrmann J. , Partington M. W. , Schinzel A. , Shapiro J. , Weaver D. D. , Opitz John M.
Published: June 2005

We report on 11 cases of amyoplasia in one of identical twins. In total, 135 patients with amyoplasia were ascertained from a study of 350 patients with multiple congenital joint contractures (arthrogryposis). These 11 cases of identical twins with amyoplasia represent 8% of our patients with amyoplasia.

At least 18 sets of twins with congenital contractures have been reported previously. However, only four of these appear to involve identical twins discordant for amyoplasia. Thus, 15 cases in which only one of identical twins are affected with amyoplasia have been identified.
Possible introduction of Huntington's chorea into Pacific islands by New England whalemen
Authors: Scrimgeour Euan M. , Opitz John M.
Published: June 2005

Huntington's disease (HD) has been reported in two isolated South Pacific islands, New Britain in Papua New Guinea, and Malaita in the Solomon Islands. The earliest presumptive choreics in these foci were born in the latter part of the 19th century, prior to the colonial period. It is known that these islands were visited by certain New England whalers in the precolonial era, and inspection of the crew lists of these whalers shows many men with surnames common to families in New England known to have produced HD individuals. In some instances, the name, age, and origin of whalemen correspond with those of known choreic individuals. It is suggested that New England whalemen carrying the trait for HD introduced the disease to these islands.
Two lethal chondrodysplasias with giant chondrocytes
Authors: Yang S. S. , Roskamp J. , Liu C. T. , Frates R. , Singer D. B. , Opitz John M.
Published: June 2005

Two infants, each with a different form of sporadic lethal chondrodysplasia, had multinucleated giant chondrocytes in resting cartilage. Both patients also had severe laryngeal stenosis and normal chromosomes. The radiographic abnormalities in one patient conformed to the recently delineated entity, atelosteogenesis (spondylohumerofemoral hypoplasia or giant cell chondrodysplasia); the other patient had an unclassified type of spondyloepiphyseal dysplasia. The findings in these two patients and the previously reported observations in spondylohumerofemoral dysplasia confirm that chondrocytic giant cells are a causally nonspecific phenomenon.
Repeated pregnancy loss
Authors: FitzSimmons Jack , Wapner Ronald J. , Jackson Laird G. , Opitz John M.
Published: June 2005

Debate persists over the value of chromosome analysis of couples with repeated pregnancy loss. Therefore, we studied the records of all patients referred to the Genetics Division at Thomas Jefferson University for repeated pregnancy loss. Couples were divided into three groups according to the reason for evaluation. In group I (two consecutive abortions) significant chromosome abnormalities were found in 1.8% of individuals; in group II (three or more consecutive abortions) 2.3% of individuals had a chromosome abnormality; and in group III (50% fetal loss) 1.8% of persons had abnormal chromosomes. These rates are lower than those reported by others, but are still ten times higher than those expected in the general population and affirm the value of doing a chromosome study in such couples.

In addition, we found increased incidence of liveborn offspring with congenital abnormalities in couples evaluated for the above indications, and found a high incidence of a family history of repeated suboptimal pregnancy outcome. The significance of these findings is discussed.
AREDYLD: A syndrome combining an acrorenal field defect, ectodermal dysplasia, lipoatrophic diabetes, and other manifestations
Authors: Pinheiro Marta , Freire‐Maia Newton , Chautard‐Freire‐Maia Eleidi A. , Araujo Leila M. B. , Liberman Bernardo , Opitz John M.
Published: June 2005

A daughter of second cousins is described as having lipoatrophic diabetes, unusual facial appearance, generalized hypotrichosis, two natal teeth with enamel dysplasia, eruption of four dysplastic deciduous teeth, absence of permanent dentition, low birth weight, short stature, lumbar scoliosis, renal alterations, aplasia of a breast and hypoplasia of the other, hypoplastic and hypopigmented areolae with diffuse limits, hyperostosis of the cranial vault, metacarpal hypoplasias, difficulty of grasping with the left hand, exertional dyspnea, absence of DIP extension and flexion creases, dermatoglyphic alterations, and other anomalies. Her sister, dead at 1 1/2 years, had had some manifestations of the condition; seven sibs are normal. It is more likely that the whole clinical picture represents a single syndrome rather than homozygosity of different autosomal‐recessive genes.
Absence of dermal ridge patterns: Genetic heterogeneity
Authors: Reed Terry , Schreiner Richard L.
Published: June 2005

An apparently new form of complete absence of dermal ridge patterns was transmitted as an autosomal dominant trait through five generations in an Irish‐American family. Affected individuals lacked dermatoglyphic patterns, sweat pores, and ability to sweat in the volar areas of the fingertips, palms, and soles. They also had congenital milia and blisters on the fingertips and soles at birth, abnormal nails, single transverse palmar creases, increased heat tolerance, and painful fissures in adult life around the fingernails in cold weather.
Origin of nondisjunction in trisomy 21 syndrome: All studies compiled, parental age analysis, and international comparisons
Authors: Juberg Richard C. , Mowrey Philip N.
Published: June 2005

The Q‐band polymorphism of chromosome 21 permits assignment of the origin of meiotic nondisjunction by parent and meiotic division in a certain proportion of cases. We have compiled all reports through 1982 (including earlier studies using structural abnormality) and have shown that maternal origin accounts for 80% and paternal origin for 20% of trisomic cases. The ratio of first:second meiotic errors among the maternal cases was 80:20 and 60:40 among the paternal cases. Considering maternal and paternal first and second meiotic errors, we showed no differences of either mean maternal or paternal age, though mean maternal age is about 5 yr higher than that of the general population. Comparison of results of six studies from five countries showed similar frequencies by parent and meiotic division with the possible exception of one study from the northeastern United States. The causative role of simply advancing maternal age in nondisjunction is questioned.
Hirschsprung disease: Etiologic implications of unsuccessful prenatal diagnosis
Authors: Jarmas Audre L. , Weaver David D. , Padilla Lillie Mae , Stecker Ellyn , Bender Harvey A. , Opitz John M.
Published: June 2005

We describe an infant with Hirschsprung disease (congenital aganglionosis of the intestine) involving the colon and terminal ileum. Midtririmester prenatal diagnosis of this disorder in this infant was attempted utilizing amniotic fluid disaccharidase analyses, ultrasound, and amniography. Decreased disaccharidase activities in amniotic fluid have been reported previously in association with other forms of intestinal obstruction. At 15 weeks' gestation, normal amniotic fluid disaccharidase levels were obtained. Serial ultrasound evaluations did not indicate any pathology, and the results from amniography were inconclusive. The implication of the normal disaccharidase values is that Hirschsprung disease may in some cases result from degeneration of intestinal ganglia after 16 weeks' gestation rather than from faulty migration of neural crest cells.

The inheritance of Hirschsprung disease is generally consistent with sex‐modified multifactorial inheritance with a lower threshold of expression in males. The case we report has a family history of three affected first‐ and second‐degree relatives. Autosomal dominance with variable expressivity is a possible explanation in this family.
Morquio B syndrome: A primary defect in β‐galactosidase
Authors: van der Horst Gijsbertus T. J. , Kleijer Wim J. , Hoogeveen André T. , Huijmans Jan G. M. , Blom Wim , van Diggelen Otto P.
Published: June 2005

Fibroblasts from patients with Morquio B syndrome contain normal numbers of β‐galactosidase molecules with normal turnover but strongly reduced activity per enzyme molecule. Various substrate affinities are abnormal: the KM for methylum belliferyl (MU)‐β‐galactoside is 4–10‐fold elevated and affinity for keratan sulphate and oligosaccharides, isolated from Morquio B urine, was not detectable. In contrast, these substrate affinities are normal for β‐galactosidase in adult type GM1‐gangliosidosis fibroblasts. Cell hybridization studies demonstrate that Morquio B syndrome and infantile and adult type GM1‐gangliosidosis belong to the same complementation group. From these results we conclude that Morquio B syndrome is caused by a mutation in the structural gene for β‐galactosidase, which is allelic to the mutations in infantile and adult type GM1‐gangliosidosis. Urinary excretion of keratan sulphate and oligosaccharides is abnormal in Morquio B syndrome but normal in adult type GM1‐gangliosidosis. The catalytic properties of β‐galactosidase in Morquio B syndrome and GM1‐gangliosidosis provide a possible explanation for the distinct clinical manifestations in these disorders.
Definition and diagnosis of the Brachmann–De Lange syndrome
Authors: Preus M. , Rex A. P.
Published: June 2005

We have classified patients referred for suspicion of the Brachmann–De Lange syndrome (BDLS) into two groups using techniques of numerical taxonomy. Patients with the syndrome share an array of abnormal characteristics, and those without it have different abnormal characteristics. A group of 30 characters that best distinguish the two groups of patients was used to construct a diagnostic index. The index score is expected to divide 99% of patients into those with and without the syndrome, leaving 1% in a “zone of doubt.” All 46 patients used to construct the index and 16 new patients had scores in either the BDLS or non‐BDLS range and none were in the zone of doubt. A previously published index using metacarpal‐phalangeal measurements, although less discriminatory, confirmed our findings in 84% of 25 patients tested, the remainder having scores in the zone of doubt for that index.
The fragile X syndrome II: Preliminary data on growth and development in males
Authors: Partington M. W. , Opitz John M.
Published: June 2005

Growth data–stature, body weight, occipito‐frontal circumference (OFC), ear length and mean testicular volume (MTV)—in 61 males with the fragile X syndrome are presented. Small increases in the mean OFC and ear length and large increases in the MTV were found. The overgrowth of the head was evident in childhood. The characteristic facial appearance was deemed to be present in 60% of the subjects and was recognizable in childhood. Macro‐orchidism (MTV of ≥ 30 ml) was present in 80% of the adults but none of the children.

Five subjects had a cleft palate, 11 serious eye disorders (3 with congenital nystagmus), and 4 had torticollis and/or kyphosis.

Limited information on development suggested that mental retardation was present from early life and was not progressive. Although 3 subjects were autistic (2 with self abuse) most were pleasant, even tempered and cooperative men and boys.
The fragile X syndrome I: Familial variation in the proportion of lymphocytes with the fragile site in males
Authors: Soudek D. , Partington M. W. , Lawson J. S. , Opitz John M.
Published: June 2005

A review of 61 males with the fragile X positive form of the Martin Bell syndrome from 30 families seen in the past 4 years suggests that the number of lymphocytes with the fragile site on the X chromosome (fra(X)) in retarded males tends to be characteristic for the individual and similar to that found in other retarded males in the same family. The number of lymphocytes with fra(X) was not correlated with height, weight, occipitofrontal circumference, ear length or mean testicular volume in adults nor with age over the whole series.
Folic acid therapy in the fragile X syndrome
Authors: Brown W. T. , Jenkins E. C. , Friedman E. , Brooks J. , Cohen I. L. , Duncan C. , Hill A. L. , Malik M. N. , Morris V. , Wolf E. , Wisniewski K. , French J. H. , Opitz John M.
Published: June 2005

Two brothers with fra(X) positive X‐linked mental retardation (XLMR) were treated with folic acid. Initially a double blind cross‐over design was employed followed by a long‐term high dose trial. A decrease in the frequency of fra(X) positive cells was observed when low folic acid culture medium was used but not when an FUdR induction system was employed. Selected behavioral characteristics improved in both while receiving folic acid. Decreased hyperactivity, greater attention span, increased motor coordination, increased quantity and quality of speech were noted. Improvement in Leiter mental age and regression after cessation of treatment was seen in one subject but not in the other. Further controlled trials with larger numbers of subjects using high doses of folic acid over longer periods of time are needed to assess the possible benefits of this experimental form of treatment.
X‐linked mental retardation associated with bilateral clasp thumb anomaly
Authors: Gareis Frank J. , Mason Jon D. , Opitz John M.
Published: June 2005

We report on a family in which mental retardation is associated with a bilateral clasp‐thumb anomaly (absent extensor pollicis brevis tendons). Males over 3 generations were documented to have this combination of findings and pedigree analysis strongly suggests X‐linked inheritance. We are not aware of previous reports of X‐linked mental retardation (XLMR) associated with this anomaly. There was no evidence of a fragile X in the 2 brothers who were studied for this abnormality.
The Golabi‐Rosen syndrome ‐ report of a second family
Authors: Opitz John M. , Opitz John M.
Published: June 2005

Golabi and Rosen (1984) have reported on a new X‐linked mental retardation/multiple congenital anomalies (XLMR/MCA) syndrome of pre‐ and postnatal overgrowth, characteristic “coarse” facial appearance with macrostomia, midline groove of tongue, lower alveolar ridge and lip, submucous cleft of palate, supernumerary nipples, intestinal anomalies, supernumerary pair of ribs, anomalies of sacrum and tailbone, hypoplastic index fingernails, postaxial polydactyly and other digital anomalies. This was an incompletely recessive trait with some manifestations evident in an obligatory carrier.

Here we report on a second family (studied at the University of Wisconsin for over 9 years) in which 3 males born to half‐sisters and their mother were affected with the Golabi‐Rosen syndrome (GRS) Overgrowth was not a prominent manifestation in these affected males. Presence of cystic kidneys, peculiar skin changes and hepatomegaly make it likely that the Golabi‐Rosen syndrome is an X‐linked MCA/dysplasia/MR syndrome. Its metabolic basis remains unknown. It seems to be an incompletely recessive trait.
An X‐linked mental retardation syndrome with craniofacial abnormalities, microcephaly and club foot
Authors: Holmes Lewis B. , Gang David L. , Opitz John M.
Published: June 2005

A male infant, who died of renal insufficiency at 6 months, had 2 similarly affected maternal uncles who died at 16 and 6 months respectively. Their manifestations include microcephaly, a large anterior fontanel, short nose with anteverted nostrils, club foot deformity, retarded psychomotor development and, in the index case only, kidney hypoplasia and dysplasia. The 2 obligatory carriers of this evidently X‐linked recessive syndrome had no physical abnormalities.
Terminal and interstitial deletions of the long arm of chromosome 7: A review with five new cases
Authors: Young R. S. , Weaver D. D. , Kukolich M. K. , Heerema N. A. , Palmer C. G. , Kawira E. L. , Bender H. A. , Opitz John M.
Published: June 2005

Sixteen cases of terminal deletions and 17 cases of interstitial deletions of the long arm of chromosome 7 have been reported to date. We present two new cases of the former and three of the latter. The somatic changes in these patients are tabulated and an update on the anomalies associated with the various cytogenetic entities is presented. Changes found in over one‐third of patients with 7q terminal deletion syndrome include: developmental delay, pre‐ and postnatal growth retardation, generalized hypotonia, abnormal electroencephalograms with or without seizures, feeding problems in infancy, microcephaly, prominent forehead, ocular hypertelorism, eye defects, broad nasal bridge, bulbous nasal tip, auricular malformations, micrognathia, chest abnormalities, genital malformations in males, and abnormal palmar and plantar creases. Evidence for the localization of the Kidd blood group gene on chromosome 7 distal to band q32, as suggested by previous reports, is reviewed; we conclude that the evidence does not warrant placement of the gene in this region of the genome.
Deletion of chromosome 15 (q11 – 13) in a Prader‐Labhart‐Willi syndrome clinic population
Authors: Cassidy Suzanne B. , Thuline Horace C. , Holm Vanja A. , Opitz John M.
Published: June 2005

Deletion of the long arm of chromosome 15 has recently been reported in a number of patients with the Prader‐Labhart‐Willi syndrome who were studied with prometaphase banding. We performed cytogenetic analysis on 12 patients with this disorder in whom the clinical diagnosis was certain. A specific cytogenetic anomaly, del(15q11 – 13) was found in all of the 12 patients. In nine of the 12, the deletion was noted in all cells examined; in two, there was mosaicism, some cells having the deletion and others being normal; one patient had a 7;15 translocation. No clinical differences were evident between individuals with mosaicism for the translocation and those with the typical deletion in all cells examined. The finding that all of our patients with Prader‐Labhart‐Willi syndrome have a cytogenetic anomaly, with some patients having mosaicism, distinguishes the results of this study from those of previous reports. Prometaphase chromosome analysis is recommended in all individuals clinically suspected of having Prader‐Labhart‐Willi syndrome and should be considered in hypotonic infants without a specific diagnosis.
Utilizing automated methods to improve estimates of recurrence risk with linked genetic markers
Authors: Price R. Arlen , Kidd Kenneth K. , Opitz John M.
Published: June 2005

Information on linked markers can greatly improve estimates of recurrence risk for genetic disorders. However, when linkage is incomplete, utilizing the information in genetic counseling requires complex, repetitive calculations to estimate correct risks whenever the parental linkage phase is not precisely known. This paper demonstrates with examples how the computer program LIPED can be used for any pedigree to estimate risk precisely within bounds determined only by confidence limits on the recombination fraction.
Acrofacial dysostosis with severe facial clefting and limb reduction
Authors: Kawira E. L. , Weaver D. D. , Bender H. A. , Opitz John M.
Published: June 2005

We describe two unrelated patients with a severe form of acrofacial dysostosis. Facial defects in both include coloboma of the lids, micrognathia, lateral oral clefting, palatal clefting, and severe auricular anomalies, with one showing bilateral cleft lip and right oblique facial clefting as well. Both have absent forearms and thumbs. Lower limbs were severely reduced in both infants with the feet attached either to the femur or directly to the trunk. Parental consanguinity was present in one case. The condition in these two infants appears to represent either a severe form of Nager acrofacial dysostosis or a new type of acrofacial dysostosis.
Mosaic inversion duplication of chromosome 15 without phenotypic effect: Occurrence in a father and daughter
Authors: Knight Louise A. , Lipson Mark , Mann John , Bachiman Ronald , Opitz John M.
Published: June 2005

A mosaic marker chromosome was observed in 2 generations. Multiple staining techniques identified it as an inverted duplication of chromosome 15 (inv dup 15) derived from the paternal grandmother. Although this inv dup 15 included a central R band, there was no noticeable phenotypic effect.
Prenatal diagnosis of chronic granulomatous disease
Authors: Matthay Katherine K. , Golbus Mitchell S. , Wara Diane W. , Mentzer William C. , Karp Laurence E.
Published: June 2005

A luminol enhanced chemiluminescence micromethod has been adapted for use in prenatal diagnosis of chronic granulomatous disease (CGD). After validation of the assay in normal adults, newborns, fetuses, CGD carriers, and CGD patients, the fetuses of two pregnant CGD carriers were tested after fetoscopic aspiration of fetal blood. Normal neutrophil chemiluminescence and nitroblue tetrazolium slide tests were followed by delivery of two healthy infants whose normality was confirmed. Amniocytes proved useless for the prenatal diagnosis of CGD. They were found to have negligible nitroblue tetrazolium reduction, oxygen metabolism, and oxygen dependence.
The consumers' views of genetic counseling of hemophilia
Authors: Markova Ivana , Forbes C. D. , Inwood M. , Optiz John M.
Published: June 2005

Twenty‐five Scottish and 22 Canadian patients with hemophilia, and 15 Scottish and 14 Canadian carriers of hemophilia participated in the study. They were interviewed with respect to their experience of and attitudes to genetic counseling, perceptions of the counselor's role, and satisfaction with existing care for families with hemophilia. Most patients and carriers favor genetic counseling as part of general counseling offered to them by the hemophilia center and think that such counseling should include dealing with such issues as schooling, employment, emotions, and psychological problems. Prenatal testing and termination of pregnancy is at present unacceptable to most of the participants, although they do not object to the use of these methods in cases of illnesses more severe than hemophilia.
Acro‐renal‐ocular syndrome: Autosomal dominant thumb hypoplasia, renal ectopia, and eye defect
Authors: Halal Fahed , Homsy Magda , Perreault Giiles
Published: June 2005

Seven individuals from 3 generations of a French‐Canadian family had various combinations of acral, renal, and ocular defects. Acral anomalies varied from mild hypoplastic distal portion of the thumbs, with limited motion at IP joint, to severe thumb hypoplasia and preaxial polydactyly. Renal anomalies varied from mild malrotation to crossed renal ectopia without fusion; other urinary tract anomalies were vesicoureteral reflux and bladder diverticula. Ocular manifestations varied from complete eye coloboma, coloboma of the optic nerve, ptosis, and Duane anomaly. The syndrome seems to be an autosomal dominant trait with high penetrance and variable expressivity. Dermatoglyphics were abnormal; in addition to a triradius t' present in all, some also had various combinations of high TRC, thenar exit of A line, and rare patterns in interdigital area IV.
The bingo model of survivorship. II: Statistical aspects of the bingo model of multiplicity 1 with application to hereditary polyposis of the colon
Authors: Morales Arlene Joan , Murphy Edmond A. , Krush A. J. , Optiz John M.
Published: June 2005

Some Mendelian disorders (Huntington chorea, hereditary polyposis coli) are not manifest at birth show a distribution in the age of onset. Patients at risk fall into three groups. In type I, they are affected when first examined. In type II, they are not affected at one visit, but are at a later visit. Those of type III (who comprise an indistinguishable mixture of those who have, and those who have not, inherited the gene) are never found to be affected. This paper posits a model that the age of onset is logistic. (It is a degenerate bingo model in which competing causes of death may be ignored.) The statistical properties of maximum likelihood estimation (MLE) are explored by Monte Carlo simulation of this logistic function with known arbitrary parameters. Two schemes are used: point‐prevalence (or synchronic) data of types I and III, and piecewise longitudinal (diachronic) data; this allows all three types to be included. Samples of various sizes between 25 and 100 are used. While estimates of the parameters are positively biased (especially with small samples), the estimate of the mean appears to be consistent, almost unbiased, and fairly precise, though somewhat larger than the estimates from the lower bound (a fact that calls for some caution in interpreting actual data). The MLE was applied to 109 patients with the Gardner syndrome (GS); measures of variability found by applying MLE to four random subsets of 25 each were compared against the asymptotic estimates. The analysis was also applied to 36 persons with familial polyposis coli (FPC). The mean age of onset in GS and FPC was similar, and since they are rather earlier than is currently believed, it is recommended that regular supervision be started at not later than 10 years of age.
Lethal multiple pterygium syndrome in an 18‐week fetus with hydrops
Authors: Isaacson Glenn , Gargus J. Jay , Mahoney Maurice J. , Optiz John M.
Published: June 2005

We present the case of an 18‐week abortus with lethal multiple pterygium syndrome and hydrops. Radiographic and anatomic study showed none of the bony abnormalities reported in live‐born children with multiple pterygium syndrome. The pathogenesis of the hydrops was not apparent. The findings of cleft palate, pulmonary hypoplasia, muscular atrophy, gracile thoracic bones, and fetal death are typical of the lethal variant.
The Bartsocas‐Papas syndrome: Autosomal recessive form of popliteal pterygium syndrome in a male infant
Authors: Papadia Francesco , Zimbalatti F. , La Rosa C. Gentile
Published: June 2005

We report on an additional patient with the severe autosomal recessive form of the popliteal pterygium syndrome. The patient was diagnosed at birth and had all of the phenotypic manifestations of this rare syndrome. Clinical findings and natural history suggest this is a distinct genetic entity.
A Genetic Study of red cell osmotic fragility in Huntington's disease
Authors: McCormack Michael K. , Lazzarini Alice , Toke David , Lepore Frederick
Published: June 2005

The erythrocyte osmotic fragility was evaluated on 19 unmedicated subjects with Huntington's disease and 42 individuals at 50% risk, 27 children at 25% risk, and a group of 60 hematologically normal control persons. Five older subjects at 50% risk for Huntington's disease as well as 6 Alzheimer's disease individuals were also evaluated for comparison.

The osmotic fragility of fresh and 24‐hour incubated red cells was analyzed and a fragility index calculated for each individual. The fragility index for the Huntington's disease group was statistically lower than that of the control group (P < .001) suggesting that the Huntington's disease erythrocytes had a reduced osmotic fragility. In the 50% risk group, 45% of the subjects demonstrated decreased osmotic fragility and 55% had normal fragility. For those subjects in the 25% risk group, 22.2% had decreased fragility and 77.8% had normal fragility. Twenty‐seven offspring were evaluated of the 14 persons at 50% risk for Huntington's disease with children; eight of the 14 individuals at 50% risk showed normal fragility and all 16 of their children showed fragility indices with the normal range. The remaining six persons at 50% risk for Huntington's disease had increased erythrocyte fragility and out of their 11 children, five showed normal fragility and six had decreased fragility.

These data support the hypothesis of reduced erythrocyte osmotic fragility in individuals affected with and at risk for Huntington disease, and demonstrate the need of further study of the erythrocyte in this complex behavioral genetic disease.
A second family with autosomal dominant osteosclerosis—type Stanescu
Authors: Dipierri J. E. , Guzman J. D.
Published: June 2005

We report the clinical, radiological and dermatoglyphic findings in a woman and her daughter affected with the autosomal dominant osteosclerosis type Stanescu.
Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: Data for genetic counselling
Authors: Bear J. C. , McManamon P. , Morgan J. , Payne R. H. , Lewis H. , Gault M. H. , Churchill D. N. , Opitz John M.
Published: June 2005

Few reports are available on the age‐related risk of relatives of affected persons to manifest adult polycystic kidney disease (APKD). For 371 persons in 17 kindreds, at risk for APKD by virtue of having an affected first degree relative, we calculated the estimated probability of clinical diagnosis of APKD to be 0.011 by age 20, 0.041 by age 30, 0.115 by age 40, 0.299 by age 50, and 0.404 by age 60 years (expected = 0.50). Ultrasonographic examination of 172 asymptomatic persons at risk showed definite APKD is 60. The probability of ultrasonographic detection of asymptomatic APKD is estimated as 0.222, 0.657, and 0.855 at age 5, 15, and 25 years, respectively. The probability of having APKD following normal ultrasonogram results (conservatively assuming 90% specificity) is estimated as 0.46, 0.28, and 0.14 for persons at 50% risk in their first, second, or third decade. The marginal benefit of ultrasound as a diagnostic test for APKD for persons in the second or third decade is estimated as 0.37 and 0.41, respectively for a “positive” test and 0.22 and 0.37 for a “negative” test.
Corneal changes, hyperkeratosis, short stature, brachydactyly, and premature birth: A new autosomal dominant syndrome
Authors: Stern Judith K. , Lubinsky Mark S. , Durrie Daniel S. , Luckasen John R. , Opitz John M.
Published: June 2005

We report on an autosomal dominant syndrome consisting of unique corneal epithelial changes, diffuse palmoplantar hyperkeratosis, distal onycholysis, brachydactyly, short stature, premature birth, and dental problems. This condition has been present in seven persons in three generations of one family. Corneal biopsies demonstrate mild dysplastic changes in the epithelium. Skin biopsies show hyper‐keratosis and acanthosis. In both eye and skin specimens, results of stains for polysaccharides, amyloid, and tyrosine were unremarkable.

Roentgenograms of the hands show short distal phalanges, short 4th metacarpals, and constriction of the heads of some of the metacarpals. In three of four affected relatives, a variable medullary narrowness is seen. In mode of inheritance, clinical appearance, and/or assoicated defects. This syndrome appears to differ from previously reported conditions that include palmoplantar hyperkeratosis and/or corneal changes.
Forearm fullness in Coffin‐Lowry syndrome: A misleading yet possible early diagnostic clue
Authors: Hersh Joseph H. , Weisskopf Bernard , DeCoster Crystal , Opitz John M.
Published: June 2005

Two unrelated infants with delayed development and suspected abnormalities of the upper limbs were found to have the Coffin‐Lowry syndrome. Both had marked fullness of the forearms in the presence of normal skeletal structures which resulted from increased subcutaneous fat. Although initially misleading, the forearm changes may serve as an early diagnostic clue in this disorder.
Prenatal diagnosis of asphyxiating thoracic dysplasia
Authors: Lipson M. H. , Waskey J. , Rice J. , Adomian G. , Lachman R. , Filly R. , Rimoin D. , Opitz John M.
Published: June 2005

A fetus at risk for asphyxiating thoracic dysplasia was studied with ultrasound examination at 16, 18, and 23 weeks of pregnancy. Definite shortness of fetal femora was observed. Radiographic and histologic examinations after pregnancy termination confirmed the diagnosis. Asphyxiating thoracic dysplasia appears to be one of an increasing number of skeletal dysplasias that can be diagnosed prenatally with ultrasound.
Serum myoglobin in Duchenne muscular dystrophy carrier detection: A comparison with creatine kinase and hemopexin using logistic discrimination
Authors: Percy Maire E. , Pichora Geoffrey A. , Chang Lebe S. , Manchester Kathryn E. , Andrews David F. , Opitz John M.
Published: June 2005

Logistic discrimination was used to assess the effectiveness of serum myoglobin (Mb), creatine kinase (CK), and hemopexin (H) measurements in identifying Duchenne muscular dystrophy (DMD) carriers. Subjects included 36 obligate carriers, 46 age‐matched control women, 30 mothers of isolated cases, and 14 DMD patients. The percentages of obligate carriers with logistic carrier probabilities exceeding the upper normal 95th centile (or 97.5th centile) were: CK alone, 63% (50%); Mb alone, 65% (62%); CK and Mb, 66% (62%); CK and H, 78% (65%); CK H and Mb, 72% (65%). In this study, Mb identified more carriers than CK at the 97.5% level, but there was no advantage in using Mb measurements with CK. CK provided slightly better overall separation of the control and carrier groups than Mb. CK, Mb, and H in combination provided significantly better separation than CK and H, or CK alone.
A molecular method for detecting the presence of the human Y chromosome
Authors: Friesen Helena , Nishioka Yutaka , Opitz John M.
Published: June 2005

The presence of the human Y chromosome can be inferred from the detection of a male‐specific 3,4‐Kb band generated by digestion with the restriction enzyme Hae III. However, direct visualization of this band is sometimes difficult owing to high background of DNA fragments common to both sexes, and Y chromosome length polymorphism. We have shown that the 3.4‐Kb band can be detected by filter hybridization to a large DNA fragment (> 20 Kb) also generated by Hae III digestion. Since this large DNA fragment is easily isolated from either sex, it should prove useful to determine sex when chromosome analysis is impractical.
Inherited metabolic myopathy with storage of glycoproteins and glycosaminoglycans
Authors: Ionasescu Victor , Pedrini Victor , Aschenbrener Carol , Ionasescu Rebeca , Searby Charles
Published: June 2005

Two related patients (mother and daughter, ages 28 and 5 years) showed mild to moderate weakness and atrophy of facial and shoulder muscles with congenital onset and minimal progression. Serum creatine kinase was elevated in the child. Muscle biopsy showed normal light‐microscopic and histochemical findings, but scattered sarcoplasmic vacuoles with storage of granular material were evident on electron microscopy. Storage of granular material was also identified in fibroblasts which were weakly PAS‐positive, stained metachromatically with toluidine blue and orthochromatically with alcian blue. Muscle glycogen values were lownormal. Repeated biochemical studies of cultured fibroblasts identified excessive storage of glycosaminoglycans and glycoproteins. The uptake of 3H‐glucosamine in cultured fibroblasts was 1.7–3.4 times greater in the patients than in control individuals, while the rate of turnover of the radioisotope was normal. These findings suggest that the genetic defect in this inherited metabolic myopathy is related to excessive synthesis of glycosaminoglycans and glycoproteins.