bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrence rate for de novo 21q21q translocation Down syndrome: A study of 112 families
Authors: Steinberg Charlotte , Zackai Elaine H. , Eunpu Deborah L. , Mennuti Michael T. , Emanuel Beverly S. , Opitz John M.
Published: June 2005

Recurrence of de novo GqGq Down syndrome (DS) in nine reported families and the low frequency of this chromosome abnormality in the population prompted this multicenter study to examine recurrence rate. Pedigrees and cytogenetic findings were analyzed from 112 families ascertained by a DS child with de novo GqGq translocation. Four of 112 sets of parents had abnormal cytogenetic findings. One mother and two fathers had a low proportion of mosaicism for trisomy 21 in peripheral lymphocytes. In one of these fathers, fibroblast studies confirmed the mosaicism (others not similarly studied). Two of these three families have one additional child each, both being normal. In the fourth family, the mother is heterozygous for a pericentric inversion of chromosome 21.

Ninety of the 112 probands had a total of 130 full sibs and 34 half sibs. None of these 164 sibs was affected; the recurrence rate could still be as high as 2% (with 95% confidence based upon calculation of a one‐tailed confidence interval). Because of the latter, the nine reports of recurrence in the literature, and the abnormal cytogenetic findings in peripheral lymphocytes in 4/112 sets of parents (3.6%), we think that caution should be exercised when counseling that the recurrence risk of this event is remote.
A syndrome of microcephaly and retinal pigmentary abnormalities without mental retardation in a family with coincidental autosomal dominant hyperreflexia
Authors: Parke Julie T. , Riccardi Vincent M. , Lewis Richard Alan , Ferrell Robert E. , Opitz John M.
Published: June 2005

We describe two brothers with severe microcephaly, unusual retinal pigmentary anomalies, intellectual function in the average or low average range, and a strong family history of hyperreflexia. The brothers have a previously undescribed syndrome, while the hyperreflexia appears to represent a coincidental autosomal dominant Mendelian trait, perhaps linked to the Kell blood group system.
Isolated tibial hemimelia in sibs: An autosomal‐recessive disorder?
Authors: McKay Marian , Clarren Sterling K. , Zorn Richard , Opitz John M.
Published: June 2005

Isolated tibial hemimelia is generally considered to occur sporadically. We report on isolated tibial hemimelia in two sibs born to phenotypically normal parents and review a similar case from the literature. These cases suggest autosomal‐recessive inheritance. Whether isolated tibial hemimelia represents a discrete syndrome or an expression of a disorder with wider phenotypic variability remains unclear.
Tandem dup(1p) within the short arm of chromosome 1 in a child with ambiguous genitalia and multiple congenital anomalies
Authors: Elejalde B. Rafael , Opitz John M. , de Elejalde Maria Mercedes , Gilbert Enid F. , Abellera Mario , Meisner Lorraine , Lebel Robert R. , Hartigan J. Michael , Breg W. Roy
Published: June 2005

A newborn infant was found to have multiple congenital anomalies including bilateral cleft of lip and palate, intrauterine growth retardation, microcephaly, tetralogy of Fallot, ambiguous external genitalia, and presence of male and female internal genitalia. Chromosome analysis showed a tandem duplication of part of the short arm of chromosome 1, resulting in a dup(1p31→35). The karyotype designation is 46,XY,dir dup(pter→31::p35→p31::p31→qter). The exact nature of the chromosome anomaly was clarified with use of several banding methods.
Oculopharyngeal and distal myopathy: A case study from papua new guinea
Authors: Scrimgeour Euan M. , Mastaglia Frank L.
Published: June 2005

Distal limb myopathy with onset at 30 years, followed by the development of progressive ptosis, external ophthalmoplegia, and pharyngeal myopathy was observed in a 37‐year‐old Melanesian man from the Gulf Province of Papua New Guinea. Ptosis and external ophthalmoplegia without apparent distal muscle involvement or dysphagia with onset at 35 and 25 years of age, respectively, were noted in the patient's 44‐ and 27‐year‐old sisters. Autosomal recessive inheritance appears to be likely in this family. This myopathic syndrome has not previously been reported in Melanesians.
Cat‐eye syndrome with unusual marker chromosome probably not chromosome 22
Authors: Rosenfeld Warren , Verma Ram S. , Jhaveri Ramesh C. , Opitz John M.
Published: June 2005

An unusual supernumerary chromosome with a single satellite on the long arm was found in a child with manifestations of the cat‐eye syndrome including apparently low‐set and malformed ears, preauricular tags, micrognathia, and imperforate anus. Although G‐banding suggested that this extra material was chromosome 22, this was not confirmed by several other banding techniques. After examination of the parents' chromosomes, the nature and origin of this extra chromosome remains obscure. We conclude that patients previously diagnosed as having “partial trisomy 22” with incomplete cat‐eye syndrome may have a different chromosome constitution when studied by various banding techniques.
Central nervous system malformations in the Kraków region. II. Case control studies on the human leukocyte antigen genotype and haplotype frequenciess
Authors: Pietrzyk Jacek J. , Turowski Gabriel , Róźański Bogdan
Published: June 2005

A case control study of human leukocyte antigen haplotypes was performed on a sample of 44 index families of children with central nervous system (CNS) malformation and 36 families of healthy newborn infants. HLA typing for antigens determined by loci A, B, and C was done on parents and offspring.

The HLA genotypes were inferred from segregation in families and the HLA gene and haplotype frequencies were obtained by direct gene counting. Casecontrol comparison did not uncover significant differences at any HLA allele. The haploytype pattern in the group of index cases did not show association with CNS malformations. The HLA phenotype compatibility among the probands' and controls' parents was within the same range except for locus C where parents of children with neural tube defects (NTD) less frequently shared common HLA‐C antigens. The segregation of paternal haploytypes showed significant deviation in the families of NTD infants.
The dynamics of quantifiable homeostasis. IV: Zero‐order homeostasis
Authors: Murphy Edmond A. , Renie William A. , Opitz John M.
Published: June 2005

A zero‐order homeostatic process is one in which the corrective force a has sign opposite to that of what the displacement from the homing value was one lag (L) time earlier, but is unrelated to magnitude of displacement. The properties of a zero‐order process are considered in some detail. Its stable state is an oscillation with a period of 4L and a maximum amplitude of aL. It is suggested that this property is exploited in evolution for intrinsically rhythmical processes, and several examples (respiration, menstruation, and heart beat) are discussed. The parameters may be modulated by an ancillary cybernetic (retreat) circuit and hence the properties of the oscillation controlled as need be. Zero‐order oscillation has means of conserving information through phase shifts. Also, when it is combined with a linear cybernetic process (with restoration constant b), it prevents information in the latter from dying out, even if Lb is less than π/2 (which in a pure linear process would ensure extinction of all signs of perturbation). A further elaboration is the Dilman process of zero order in which there is a threshold of displacement below which homeostatic responses are not evoked. The merits of the value of the threshold are discussed. The properties of the zero‐order process with a first‐order retreat function furnish a tentative explanation for why hormonal homeostasis does not operate directly through the pituitary but involves the hypothalamus and intermediate hormone‐releasing factors.
Phenotypic variability in Townes‐Brocks syndrome
Authors: de Pina‐Neto João Monteiro , Opitz John M.
Published: June 2005

This is a report on a child with sensorineural deafness, imperforate anus with rectovaginal fistula, hypoplastic thumb, and congenital heart defect. This pattern of congenital anomalies is similar to that described in patients with the Townes‐Brocks syndrome, although the present patient has characteristics that have not been reported previously in this syndrome. It is proposed that the clinical spectrum of the Townes‐Brocks syndrome must be extended to include congenital heart defect, auricular changes differing from those previously described, and anomalies of other internal organs. The syndrome is an autosomal dominant trait. The present case may represent a de novo mutation.
The pathophysiology of neurofibromatosis: IX. Paternal age as a factor in the origin of new mutations
Authors: Riccardi Vincent M. , Dobson Christopher E. , Chakraborty Ranajit , Bontke Catherine , Opitz John M.
Published: June 2005

Von Recklinghausen neurofibromatosis is characterized by a relatively large proportion of apparently nonfamilial cases, presumed spontaneous mutations. This paper analyzes the distribution of paternal and maternal ages for 187 patients with von Recklinghausen disease representing the first definite case in their respective families. Mean paternal age was 32.8 years and mean maternal age was 27.4 years, both being significantly greater than for control populations (P equal to or less than.001). The advanced paternal age was not accounted for by the increase in maternal age. The methodology of controlling the general population paternal ages for each patient's birth year is described.
Cardiovascular findings in congenital contractural arachnodactyly: Report of an affected kindred
Authors: Anderson Richard A. , Koch Sandra , Camerini‐Otero R. Daniel , Opitz John M.
Published: June 2005

Three generations of a kindred had a history and physical findings consistent with congenital contractural arachnodactyly (CCA) segregating in an autosomal‐dominant manner. Six of the seven affected patients we examined had mitral valve prolapse (MVP) diagnosed clinically or by echocardiography. The family members without CCA did not have MVP. This association of cardiac involvement with CCA further lessens the distinction between CCA and the Marfan syndrome. The indication for ophthamologic and echocardiographic follow‐up of patients carrying the diagnosis of CCA is stressed.
Analysis of gross anatomical variations in human triploidy
Authors: Moen David W. , Werner Joan K. , Bersu Edward T. , Opitz John M.
Published: June 2005

Three cases of human triploidy were dissected in detail to determine whether or not there are any specific patterns of morphologic variation associated with this form of polyploidy. No specific constellations of anatomic variation were observed. However, each body did have a greater than normal number of variations among muscles that tend to be variable in the normal population. Two bodies showed a marked increase in the size of the thigh muscles, two bodies had eyeballs that were larger than normal, and two bodies had anomalous attachments of the extraocular muscles. The sample size is not large enough to draw any specific conclusions concerning the pathogenesis of these variations. However, the findings do suggest that careful examination of additional specimens will be of value in providing further information about the genotype/phenotype relationships in human triploidy.
Syndromes with lissencephaly. I: Millerdieker and Norman‐Roberts syndromes and isolated lissencephaly
Authors: Dobyns William B. , Stratton Robert F. , Greenberg Frank
Published: June 2005

Lissencephaly (smooth‐brain) is an abnormality of brain development characterized by incomplete neuronal migration and a smooth cerebral surface. At least 2, and possibly more, distinct pathological types occur, each associated with several distinct syndromes. In this paper, the manifestations of 3 disorders associated with type I (classical) lissencephaly are discussed, including the Miller‐Dieker syndrome with or without deficiency of 17p13, Norman‐Roberts syndrome, and isolated lissencephaly sequence.
Johann Friedrich Meckel the Younger (1781–1833)
Authors: Seidler Eduard , Mullen Pierce , Opitz John M.
Published: June 2005

On the occasion of the 200th anniversary of the birthday of Johann Friedrich Meckel the Younger (1781–1833) it is appropriate to examine his contributions to the field of clinical genetics. Special emphasis is given to his laws of “diversity” and “reduction.” These deal respectively with the evolutionary and developmental differences between organisms and the reasons for similarities in development of parts of an organism and the parts of different organisms. Meckel is an important pioneer of modern clinical teratology because he did not restrict his studies to normal development, but rather concentrated on its aberrations in his reflections on the history of development.
Response to the first Meckel oration by Sewall Wright
Authors: Opitz John M.
Published: June 2005

It is a pleasure for me to thank Sewall Wright for preparing and delivering the first Meckel oration, and I deeply appreciate the privilege of commenting on Dr. Wright's paper. The implications of Wright's work for clinical developmental genetics might not be completely clear to a nonclinical geneticist and I have therefore taken the liberty of distilling the following three major concepts out of Sewall Wright's writings on developmental genetics from 1923–1960.
Contributions of mammalian embryo transfer to developmental genetics
Authors: Kraemer Duane C. , Opitz John M. , Renolds James F.
Published: June 2005

The process of transferring preimplantation embryos from the reproductive tract of one female to that of another, commonly referred to as embryo transfer(ET), has been used extensively for exploration of basic mechanisms of developmental genetics. ET has also permitted practical application of such basic knowledge to selective breeding of livestock and treatment of infertility. Contributions of mammalian embryo transfer are presented as they pertain to studies of heredity vs environment, gamete maturation, fertilization, differentiation, and genetic transformation. Future applications of embryo transfer to the study of developmental genetics are likely to include extensive use of microsurgical techniques on a wide variety of mammalian embryos.
The Meckel syndrome in Finland: Epidemiologic and genetic aspects
Authors: Salonen Riitta , Norio Reijo , Opitz John M. , Reynolds James F.
Published: June 2005

Estimates of the incidence of the Meckel syndrome (MS) from different parts of the world vary from 1:140,000 to 1:13,250 births. In this nationwide study performed in Finland, the incidence of 1:14,400 births was found by retrospective ascertainment during the period 1970–1979, while the incidence was 1:8,500 births when prospective monitoring was performed in 1980–1981. The most probable incidence in Finland is about 1:9,000 births.

Autosomal recessive inheritance of MS is confirmed in this study. The ratio of affected sibs, corrected for truncate complete ascertainment, was 0.261. No consanguinity between parents was found, as marriages between close relatives are rare in Finland and the ancestors were not traced back far enough to find remote consanguinities.
A “new” lethal multiple congenital anomaly syndrome: Joint contractures, cerebellar hypoplasia, renal hypoplasia, urogenital anomalies, tongue cysts, shortness of limbs, eye abnormalities, defects of the heart, gallbladder agenesis, and ear malformations
Authors: Rutledge Joe C. , Friedman J. M. , Harrod M. J. E. , Currarino G. , Wright C. G. , Pinckney L. , Chen H.
Published: June 2005

Three cases of a lethal malformation syndrome with severe visceral anomalies were seen in two families and include one pair of sibs. The predominating external manifestations are mesomelic dwarfism, micrognathia, V‐shaped upper lip, microglossia, thick alveolar ridges, ambiguous genitalia, webbed neck, highly arched palate, clubfeet, fused fontanelles, inclusion cysts of the tongue, four‐finger creases, digital anomalies, apparently low‐set ears, widely spaced nipples, and dislocated thighs and forearms. The internal findings include oligopapillary renal hypoplasia, severe congenital heart defect, cerebellar hypoplasia, pulmonary hypoplasia, hypoplastic larynx, and hypoplastic gallbladder. Other findings from the two autopsies and one clinical investigation not documented in all three patients include unilobar lungs, hydrocephalus, cataracts, microphthalmia, polydactyly, islet cell hyperplasia, suprapubic skin crease, urethral anomalies, and a decreased number of turns of the cochlea. The hypoplasia seen in the several affected organs is similar to the disordered development seen in experimental models of branching epithelial morphogenesis in which mesenchymal‐epithelial interaction has been disrupted.
Arteriohepatic dysplasia (Alagille syndrome): Extreme variability among affected family members
Authors: Shulman Sally A. , Hyams Jeffrey S. , Gunta Radiskrishna , Greenstein Robert M. , Cassidy Suzanne B.
Published: June 2005

We describe a three‐generation family in which five individuals have arteriohepatic dysplasia (Alagille syndrome) with striking differences in the degree of severity. Two sisters presented with neonatal jaundice, peripheral pulmonic stenosis, and characteristic facial appearance including a broad forehead, deep‐set eyes, prominent nose, and pointed chin. One died at 5 years of cirrhosis with portal hypertension and the other at 18 months of congestive heart failure. Their asymptomatic 32‐year‐old mother and 35‐year‐old maternal aunt have a similar facial appearance, pulmonic stenosis, skeletal anomalies, and bilateral posterior embryotoxon. Neither has evidence of clinical liver disease. The maternal grandfather, who refused evaluation, has a similar appearance, a history of liver disease, and a heart murmur.

Extreme intrafamilial variability has not been reported previously and most affected individuals described in the past have followed a benign course. The pattern of severity in this family suggests the possibility of a maternal factor augmenting the clinical expression in affected offspring. The skeletal anomalies and posterior embryotoxon are valuable signs in detecting asymptomatic but affected individuals who are at risk for having offspring with this potentially lethal condition.
Genetic polymorphisms among Bukharan and Georgian Jews in Israel
Authors: Levene C. , Steinberg A. G. , Friedlander Y. , Brautbar C. , Cohen T.
Published: June 2005

Bukharan and Georgian Jews have lived in central Asia for many centuries. Approximately 30,000 Bukharan and 37,000 Georgian Jews lived in their respective countries within the USSR between 1920 and 1960. Genetic markers of blood—blood groups, isoenzymes, HLA antigens, and gamma and kappa chain allotypes—were tested in blood samples from 113 Bukharan and 134 Georgian Jews living in Israel. Estimates of inbreeding were low: α = 0.0088 for Bukharan and α = 0.0011 for Georgian Jews. G6PD deficiency was relatively rare in Bukharan (2.2%) and in Georgian Jews (6.0%), when compared to other Jews in the area. Both populations showed frequencies of some markers similar to that of other Jewish populations, but frequencies of several markers were extremely high or low. Bukharan Jews showed very high frequencies of B(0.243), cDe (0.122), JkA (0.705), HLA‐A29(0.167), A30 (0.116) and B7 (0.124), and AcPA (0.451) and very low ones of O(0.518), CDe(0.422), AcPB (0.513) and GLO1 (0.140). Very high frequencies in Georgian Jews were observed for cDE (0.189), HLA‐A3 (0.194), Bw35 (0.300) and GLO1 (0.367). Yet the greatest difference between both populations was in African characters. While in Bukharan Jews Fy was very frequent (0.146) and cDe was the highest observed among Jews (0.122), neither of these markers was detected among the Georgian Jews tested. Yet, another African character, the Gm1,5,10,11,13,14,17,26 haplotype, occurred in both populations (0.028 and 0.042 in Bukharan and Georgian Jews, respectively).

Distance measures for Bukharan, Georgian, Iranian, Cochin, and Libyan Jews based on 13 polymorphic loci showed the greatest distance between Cochin Jews and the other populations and the smallest distance between the Georgian and Iranian Jews.
Elevated alpha‐fetoprotein and acetylcholinesterase associated with hydrocele
Authors: Verp Marion S. , Milunsky Aubrey , Simpson Joe Leigh , Graham Annie , Sabbagha Ruby
Published: June 2005

Elevated amniotic fluid alpha‐fetoprotein and presence of acetylcholinesterase were detected in a pregnancy that resulted in an infant whose only abnormality was a hydrocele. Although these amniotic fluid findings are usually indicative of a serious fetal anomaly, our report indicates that this is not always the case.
Prospective management of exstrophy of the cloaca and myelocystocele following prenatal ultrasound recognition of neural tube defects in identical twins
Authors: McLaughlin John F. , Marks William M. , Jones Gary
Published: June 2005

We describe identical twins concordant for exstrophy of the cloaca and myelocystocele. Their management and subsequent course was strongly influenced by prenatal ultrasound recognition of neural tube defects in both twins and severe renal dysplasia in one of the fetuses. The genetic aspects of this case are consistent with existing causal theories of exstrophy of the cloaca.
Ruvalcaba syndrome: Autosomal dominant inheritance
Authors: Sugio Yoshitsugu , Kajii Tadashi
Published: June 2005

A kinship is described in which nine individuals in four generations were affected with the Ruvalcaba syndrome including postnatal growth retardation, an oval face with a high forehead, antimongoloid slant of palpebral fissures, small beaked nose with hypoplastic nasal alae, small downturned mouth with thin vermilion borders, pointed chin, and short fingers and toes. Less frequently seen were osteochondritis of the lumbar vertebral bodies, cone‐shaped epiphyses of the phalanges, and narrow diaphyses of the metacarpals and metatarsals. None of the affected individuals was mentally retarded. The propositus, a 3‐year‐old boy, and his mother were typically affected, while his 8‐month‐old sister, the 55‐year‐old maternal grandfather, and his 46‐year‐old younger sister had several of these manifestations. Information on the remaining four affected relatives was incomplete. The syndrome was transmitted in a dominant fashion with variable expressivity. There were two instances of male‐to‐male transmission. This effectively ruled out X‐linked inheritance. The transmission of the syndrome in three other reported pedigrees was also compatible with autosomal dominant inheritance with variable expressivity and incomplete penetrance.
HLA typing in Bartter syndrome
Authors: Delaney Vera , Watson A. J. , Pollack Marilyn , Dupont Bo , Bourke E.
Published: June 2005

The mode of inheritance of Bartter syndrome is unclear; however, autosomal recessive inheritance seems likely. A consistent genetic marker of the carrier state likewise remains elusive. HLA typing was done in a family in whom six of 12 sibs have the syndrome. No significant HLA‐syndrome linkage was found. This is in contrast to another familial hypokalemic syndrome in which a significant HLA association was found.
Balanced rearrangement of chromosomes 2, 5, and 13 in a family with duplication 5q and fetal loss
Authors: Evans Mark I. , White Beverly J. , Kent Stephen G. , Levine Michael A. , Levin Sondra W. , Larsen John W.
Published: June 2005

We have studied a family in which a mother and daughter (the proposita) had the karyotype 46,XX,ins(2;5),t(5;13). The mother had four spontaneous abortions, a mentally retarded son with duplication (5q), and a daughter who died at 3 months. The proposita had a phenotypically abnormal abortus. Rearrangements involving several chromosomes are very rare. Observations on this family are consistent with the predicted high likelihood of reproductive loss.
Deletion of the long arm of the Y chromosome and review of Y chromosome abnormalities
Authors: Fitch Naomi , Richer Claude‐Lise , Pinsky Leonard , Kahn Amnon , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a patient whose karyotype is 45,X/46,Xdel(Y) (pter→q11.212). We also present a review of literature on the Y chromosome in which evidence is presented that there are genes on the Y chromosome that prevent Ullrich‐Turner syndrome manifestations; aid in testes maturation and spermatogenesis; and affect height, tooth size, and bone maturation.
X;14 translocation: An exception to the critical region hypothesis on the human X‐chromosome
Authors: Markovic Vjerica D. , Cox Diane W. , Wilkinson John , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a family in which an X;14 translocation has been identified. A phenotypically normal female, carrier of an apparently balanced X‐autosome translocation t(X;14) (q22;q24.3) in all her cells and a small interstitial deletion of band 15q 112 in some of her cells had 2 offspring. She represents a fifth case of balanced X‐autosome translocation with the break point inside the postulated critical region of Xq(q13 q26) associated with fertility. The break point in this case is located in Xq22, the same band as in four previously published exceptional cases. In most of her cells, the normal X was inactivated.

Her daughter, the proposita, has an unbalanced karyotype 46,X,der(X), t(X;14)(q22;q24.3)mat, del(15)(q11.1q11.3)mat. She is mildly retarded and has some Prader‐Willi syndrome manifestations. She has two normal 14 chromosomes, der(X), and deletion 15q11.2. Her clinical abnormalities probably could be attributed to the deletions 15q and Xq rather than 14q duplication. In most of cells, der(X) was inactivated. We assume that spreading of inactivation was extended to the 14q segment on the derivative X. Late replication and gene dose studies support this view. Another daughter, who inherited the balanced X;14 translocation and not deletion 15 chromosome, is phenotypically normal.
X‐linked dominant chondrodysplasia punctata: A case report and family studies
Authors: Mueller R. F. , Crowle P. M. , Jones R. A. K. , Davison B. C. C. , Opitz John M. , Reynolds James F.
Published: June 2005

Two major types of chondrodysplasia punctata have been delineated; a severe, recessively inherited, rhizomelic form and the less severe, dominantly inherited Conradi‐Hünerman form. Clinico‐genetic analysis of this latter form of CP uncovered a sub‐group characterised by asymmetric involvement with linear or whorled skin patches of ichthyosiform erythroderma or atrophoderma, circumscribed cicatricial alopecia, asymmetrical cataracts and limb shortness. The mosaic pattern of the manifestations and the limitation of reported cases to females suggested an X‐linked dominant gene which undergoes Lyonisation in the female and is lethal in the hemizygous male. We report on a family ascertained through a baby girl who had manifestations typical of the X‐linked dominant form of CP and whose mother, 2 of 3 maternal aunts, and maternal grandmother all had less severe manifestations. The absence of male offspring for 3 generations and a history of 3 early miscarriages, along with the clinical variability in the affected females, provide further support for X‐linked dominant inheritance of this disorder.
Brief cytogenetic report on maternal translocation t(7;9)(p22:p23): Two sibs with duplication 9p and one sib with the balanced translocation
Authors: Wajntal Anita , Gonzalez Claudette H. , Koiffmann Célia P. , de Souza Deise H. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a family in which a maternal translocation (7;9) (7qter → 7p22::9p13 → 9pter; 9qter → 9p13) resulted in 2 sibs with dup(9p) syndrome, one sib with the same balanced constitution as the mother, and one normal boy.
Segregation and linkage analysis of α‐N‐acetyl‐D‐glucosaminidase (NAG) levels in a black family
Authors: Pericak‐Vance M. A. , Vance J. M. , Elston R. C. , Namboodiri K. K. , Fogle T. A. , Opitz John M. , Reynolds James F.
Published: June 2005

α‐N‐acetyl‐D‐glucosaminidase (NAG) activities were evaluated on serum samples from 67 persons in a large black family. These data were analyzed in conjunction with those from 126 previously tested unrelated blacks [Vance et al, 1980]. After loge tranformation, admixture analysis indicated a significantly better fit (P < .01) of a mixture of 2 normal distributions for NAG activity versus a single normal distribution. Segregation analysis using the transmission probability model of Elston and Stewart [1971] demonstrated that a genetic model fits the data better than the random “environmental” model. Thus, the existence of a major gene is suggested in the family, although the possibility of polygenic or other familial effects cannot be ruled out. These results confirm the existence of a polymorphism for NAG reported earlier in a series of White half‐sib twin families [Vance et al, 1980]. However, the estimates of the means of the three genotypes (AA, AA′, A′A′) appear to differ in the two racial groups. Thus, the data suggest either a racial polygenic effect and/or different alleles segregating in the two populations. In fact, thermal stability data [Vance et al, 1981a] suggest that at least two alleles are structurally distinct. Linkage analysis of the pedigree with 20 marker loci gave no clear indication of linkage. A lod score of 1.44 was found at 0 recombination with orosomucoid (ORM).
X‐linked motor‐sensory neuropathy type‐II with deafness and mental retardation: A new disorder
Authors: Cowchock F. Susan , Duckett Serge W. , Streletz Leopold J. , Graziani Leonard J. , Jackson Laird G. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a family with an apparently X‐linked neuromuscular disease. Electrophysiologic tests and electron microscopic studies are consistent with the diagnosis of hereditary motor sensory neuropathy type II (HMSN‐II), one form of Charcot‐Marie‐Tooth disease. The manner of inheritance, the observation that males are severely affected from infancy, and the frequent association of deafness and/or mental retardation with the neuromuscular disorder are not usual for HMSN‐II and suggest that this family may have a previously undescribed genetic disorder. The peripheral neuropathy did not appear to be linked to the Xg blood group. Minor abnormalities of sensory nerve conduction, electromyography, and hearing were separately identified in female relatives in this family, but were not consistent enough to be useful in the identification of carriers for this gene.
A lethal autosomal recessive syndrome of multiple congenital contractures
Authors: Herva Riitta , Leisti Jaakko , Kirkinen Pertti , Seppänen Ulpu , Opitz John M. , Reynolds James F.
Published: June 2005

We describe 16 cases of a lethal syndrome with multiple congenital contractures from ten families. The main clinical findings included intrauterine growth retardation with marked fetal hydrops, multiple contractures, and facial abnormalities, especially micrognathia. At autopsy, pulmonary hypoplasia and muscular atrophy were present. There was a paucity of anterior horn motor neurons in the four studied cases. We think that the cases represent the same clinical entity, probably caused by homozygosity of an autosomal recessive gene. The syndrome resembles the Pena‐Shokeir I syndrome, but seems to differ in some respects, including length of survival and presence of hydrops. Prenatal diagnosis of this syndrome is possible after the 16th week of pregnancy with ultrasound.
Genetic amniocentesis: A twelve years' experience
Authors: Dacus John V. , Wilroy Robert S. , Summitt Robert L. , Garbaciak John A. , Abdella Thomas N. , Spinnato Joseph A. , Luthardt Frederick W. , Flinn George S. , Lewis Beverly A. , Mahoney Maurice J.
Published: June 2005

The first 2,013 fetuses in 2,000 patients undergoing genetic amniocentesis at our institution were analyzed for the incidence of abnormal findings and for the safety and accuracy of the procedure. One percent of the patients were found to have aneuploid fetuses and another 1% were found to have elevated amniotic fluid concentrations of alpha‐fetoprotein. Advanced maternal age was the indication for amniocentesis in 84% of the women with aneuploid fetuses. Thirty‐two (1.6%) of the pregnancies ended in spontaneous abortion and 35 (1.7%) were terminated because of abnormal results of the prenatal diagnostic procedure. Our error rate was 0.15%, and tissue culture was successful in 97.7% of the procedures. During the latter part of our experience concurrent ultrasonography was utilized with the amniocentesis, resulting in a reduction in blood‐tinged specimens from 15.0% to 5.2%. In experienced hands, midtrimester amniocentesis for the purpose of prenatal diagnosis of genetically determined defects is a safe, accurate, and valuable procedure for the identification of fetal abnormalities.
Carpenter Syndrome: Natural history and clinical spectrum
Authors: Robinson Luther K. , James Hector E. , Mubarak Scott J. , Allen Elizabeth J. , Jones Kenneth L. , Opitz John M. , Reynolds James F.
Published: June 2005

Recently, we evaluated three sibs with Carpenter syndrome, permitting further clinical, orthopedic, radiographic, and psychometric delineation of this disorder. All three patients were operated on for craniostenosis at or before 2 months. Although all had gross motor delay in early infancy, two had normal intelligence at 12 months and 10 years, respectively. Bony abnormalities contributed to functional impairment especially in the older children. Preaxial polydactyly of feet was present in all three affected sibs and in all other reported individuals with this condition, allowing differentiation of Carpenter syndrome from the other autosomal‐recessive acrocephalopolysyndactyly syndromes.
An anatomical study of a duplication 6p based on two sibs
Authors: Smith Barbara S. , Pettersen James C. , Opitz John M. , Reynolds James F.
Published: June 2005

Dup (6p) patients have a peculiar facial appearance (frontal bossing, hypotelorism, hypoplastic midface), low birthweight, cardiovascular defects, small kidneys, and psychomotor retardation. We thought that a detailed anatomical dissection would more precisely define the syndrome, which has been developed from clinical evaluations and autopsy reports. Our patient, a female adolescent, died at 17 11/12 years and is the oldest patient with this syndrome to be described.

The brain and skull showed the greatest number of abnormalities. The brain was smaller than normal and abnormally shaped. Many of the skull abnormalities, including shortened basisphenoid/basiocciput, reduced size of cranial fossae, and steep orbital roofs, may be attributed to the brain's shape. There were no olfactory bulbs, and only one rudimentary olfactory tract was present.

Other findings were the following: a high interventricular septal defect and right ventricular hypertrophy, absence of uterus and vagina, hypoplastic ovaries, a common mesentery, two left extensor indicis bellies, bilateral absence of palmaris brevis and of peroneus tertius.

Our results are compared with anomalies found in other aneuploidy syndromes. Variations in some organ systems may be similar to those whose presence Shapiro [(1983):] has attributed to amplified developmental instability. Relationships between the brain shape and size and skull abnormalities are also discussed.

From 16 reported cases, a detailed autopsy report of the affected brother, and our anatomical findings, we suggest that this syndrome may also be characterized by arhinencephaly, common mesentery, absent uterus in the female, and growth retardation in those surviving the neonatal period.
The frequency and economic burden of genetic disease in a pediatric hospital in Mexico city
Authors: Carnevale Alessandra , Hernández Maricela , Reyes Raquel , Paz Fernando , Sosa Cristina , Opitz John M. , Reynolds James F.
Published: June 2005

A survey of 2,945 admissions to the National Institute of Pediatrics, México, was undertaken to document the frequency and burden of genetic disorders. Patients were classified into five categories: 1) single gene disorders; 2) chromosomal disorders; 3) complex genetic etiology; 4) unknown etiology, and 5) nongenetic disorders.

Of all admissions studied, 4.3% had a genetic disease (categories 1 and 2); 33.5% had a partly genetic condition (category 3); 13.8% had a disorder of unknown etiology; and 48.4% had an environmental disease.

In terms of economic burden, patients with genetic or partly genetic disorders came more frequently from outside the city and had more and longer admissions with a higher number of surgeries. The results suggest that genetic disease, although less frequent than disease caused by environmental conditions, lays a considerable financial burden on the hospital and on the affected families.

The need to create genetic units in developing countries is emphasized.
Partial deletion of distal 17q
Authors: Bridge Julie , Sanger Warren , Mosher Gayle , Buehler Bruce , Nelson Robert , Welsh Melonie , Newland James , Kafka Michael , Opitz John M. , Reynolds James F.
Published: June 2005

A newborn female was found to have a deletion of the terminal portion of 17q. Prominent manifestations included microcephaly, apparent hypertelorism, epicanthic folds, a broad nasal bridge with anteverted nostrils, posteriorly angulated ears, micrognathia, widely spaced nipples, arachnodactyly with proximal thumbs, and a coxa vara deformity. The unbalanced translocation was inherited from the mother, who had a reciprocal translocation involving the terminal portions of 2p and 17q. To the best of our knowledge, this is the first report of a liveborn infant with deletion of the distal portion of 17q with the exception of reports of patients with ring chromosome 17.
Sibs with the fetal akinesia sequence, fetal edema, and malformations: A new syndrome?
Authors: Toriello Helga V. , Bauserman Steven C. , Higgins James V. , Opitz John M. , Reynolds James F.
Published: June 2005

Pena and Shokeir [J Pediatr 85:373–375. 1974] first described a syndrome characterized by multiple ankyloses, camptodactyly, facial anomalies, and pulmonary hypoplasia, which was later termed Pena‐Shokeir I syndrome. Recent evidence suggests that a more accurate designation for this condition is the fetal akinesia sequence, which is almost certainly a heterogeneous entity. We describe sibs who were diagnosed as having Pena‐Shokeir I syndrome but who did not have the muscular or anterior horn cell changes characteristic of other infants with the fetal akinesia sequence. In addition, both sibs had fetal edema, the first sib had coarctation of the aorta, and the second had polydactyly and thyroid hypoplasia. We suggest that this case provides further evidence for heterogeneity in the fetal akinesia sequence and may represent a provisionally unique syndrome.
Prenatal diagnosis and management of congenital heart defect: Significance of associated fetal anomalies and prenatal chromosome studies
Authors: Wladimiroff J. W. , Stewart P. A. , Sachs E. S. , Niermeijer M. F. , Opitz John M. , Reynolds James F.
Published: June 2005

A fetal cardiac defect was found prenatally by ultrasound in 13 of 230 women (5.6%) with a suspected fetal anomaly. Pregnancy duration varied between 17 and 39 weeks (mean 28 weeks). The reasons for referral of the 13 patients were: suspected fetal structural defect (n = 4), oligo‐ or polyhydramnios (n = 2), severe fetal growth retardation (n = 1), fetal cardiac arrhythmia (n = 1), or a combination thereof (n = 5). Abnormal chromosomes were found in 5 out of 13 fetuses (38%)—ie, four through prenatal and one through postnatal analysis.

The present study demonstrates that fetal cardiac structural anomalies often are diagnosed in combination with ultrasonically established associated abnormality. Cytogenetic analysis of amniotic cells greatly improves diagnosis and obstetric management, especially when the cardiac defect per se is considered amenable to surgical treatment and other major structural defects have been ruled out.
Autosomal recessive deafness with skeletal dysplasia and facial appearance of Marshall syndrome
Authors: Miny Peter , Lenz Widukind , Opitz John M. , Reynolds James F.
Published: June 2005

We report on two sibs born to consanguineous parents with clinical and radiological features closely resembling those previously described by Insley and Astley [1974]. This observation provides further evidence for a distinct autosomal recessive condition with the facial appearance of Marshall syndrome, deafness, and skeletal dysplasia.
Erythrocyte catechol‐O‐methyltransferase activity: Genetic analysis in nuclear families with one child affected by down syndrome
Authors: Brahe C. , Serra A. , Morton N. E. , Opitz John M. , Reynolds James F.
Published: June 2005

Erythrocyte catechol‐O‐methyltransferase (COMT) activity was measured in 142 members of 32 nuclear families in which one child had Down syndrome (DS). The mean activity in subjects with trisomy 21 appears higher than in parents and sibs, though not significantly so. However, this fact does not seem to modify the properties expected for a trait genetically controlled in a diploid population. The commingling analysis of the COMT activity in the whole group, and in each subgroup of relatives, suggests a mixture of two or, more likely, three components, the latter being in agreement with a transmission model of genes without dominance. The most parsimonious hypothesis supported by the mixed model segregation analysis is that of an additive major locus (d = 0.5) with an estimated frequency of 0.40 ± 0.03 for the COMTH gene, to which a small polygenic effect (H = 0.067) can be added. This hypothesis is supported further by the analysis of family resemblance, r = 0.45 ± 0.12 being the maximum likelihood estimator of the intraclass correlation among sibs. The higher COMT activity in DS subjects may reflect a situation of general enzyme disorder only indirectly connected with trisomy of chromosome 21.
The dynamics of quantifiable homeostasis. Vi: Processes of fractional order
Authors: Murphy Edmond A. , Opitz John M. , Reynolds James F.
Published: June 2005

In a previous paper [Murphy and Renie, 1984] we noted that in a system that exhibits homeostasis of zero order, an instantaneous perturbation, however small, invariably leads to a permanent, stable oscillation, the amplitude of which depends on the restoration constant (b) and the lag time (L) but not on the magnitude or sign of the original perturbation. We suggested that such a remarkable property, so easily attained, would be a valuable and plausible evolutionary device for generating those cyclical processes so important in normal physiology — such as respiration, heart contraction, the sleep cycle, seasonal effects, and menstruation. By a suitable choice of parameters, they could be readily tuned to the requisite length of the cycle and amplitude of variation. The most immediate argument against this suggestion is the implausible form of the wave generated in the zero‐order process, which is angular and quite unlike anything in common experience of normal physiology.

Then in a subsequent study [Renie and Murphy, 1984] we found that for homeostatic processes of higher order, in general there is a critical value of the restoration constant at which regular oscillation is maintained. A preliminary study suggested that for processes of fractional order, no critical value that produces oscillation exists. However, the topic of processes of fractional order seems to be of sufficient complexity to warrant detailed treatment in a separate paper.
Prenatal diagnosis of Jeune syndrome
Authors: Elejalde B. Rafael , De Elejalde Maria Mercedes , Pansch Donald , Opitz John M. , Reynolds James F.
Published: June 2005

We describe two sibs affected with Jeune syndrome. The first was diagnosed after birth and the second was diagnosed prenatally using ultrasonography. The detected abnormalities were confirmed by X‐ray and autopsy following pregnancy termination. This observation indicates the possibility of prenatal diagnosis of the condition.
Differential diagnosis in young women with oligomenorrhea and the pseudopseudohypoparathyroidism variant of Albright's hereditary osteodystrophy
Authors: Halal Fahed , Van Dop Cornelis , Lord Julien , Opitz John M. , Reynolds James F.
Published: June 2005

Oligomenorrhea was the reason for consultation in three individuals (two sisters and one unrelated woman) with the pseudo‐pseudohypoparathyroidism (PPHP) variant of Albright's hereditary osteodystrophy (AHO). All had short stature, Ullrich‐Turner‐like signs, acral anomalies typical of AHO/brachydactyly E, and hypogonadism. One of the three individuals also had reduced erythrocyte Ns (a membrane nucleotide regulatory protein that is required for functional coupling of stimulatory hormone receptors and catalytic adenylate cyclase) activity as described in the pseudohypoparathyroidism variant of AHO. The differential diagnosis of young women with the PPHP phenotype is discussed with special reference to Ullrich‐Turner syndrome, brachydactyly E, the “resistant ovary” syndrome, and acrodysostosis.
Phenotype‐karyotype correlations in dup(18q): Report of a case and review
Authors: Razavi‐Encha Férechté , Raoul Odile , Lescs Marie‐Claude , Danan Claude , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a case of dup(18q) due to de novo translocation 46,XX,‐21,t(18;21)(18qter→cen→21qter). The patient had many characteristic signs of full trisomy 18 except for internal organ malformations and early death. We review the phenotype‐karyotype correlations between full trisomy 18 and dup(18q) and discuss the possibility of the existence of “critical zone(s)” at the proximal or/and distal region of 18q responsible for most signs of trisomy 18, such as congenital heart defect and early death.
A new X‐linked mental retardation syndrome
Authors: Atkin Joan F. , Flaitz Katherine , Patil Shivanand , Smith Wilbur , Opitz John M. , Reynolds James F.
Published: June 2005

We have studied a three‐generation family with 11 moderately to severely retarded males and three mildly retarded females (presumably manifesting carriers). The patients have a phenotype different from that of all other previously described types of X‐linked MR (XLMR). These include short stature, macrocephaly, “coarse” facial appearance including prominent forehead and supraorbital ridges, hypertelorism, broad nasal tip with anteverted nostrils, and thick lips. All postpubertal males had macroorchidism (volume >25 ml). Chromosomes were normal including fragile X analysis. X‐ray findings of skull, spine, and hands were normal. The intellectually normal relatives do not resemble their affected relatives except for increased head size and testicular size. These findings suggest a new variant of XLMR different from fragile X‐linked MR, the Coffin‐Lowry syndrome, and other XLMR conditions.
Apert syndrome with frontonasal encephalocele
Authors: Waterson John R. , DiPietro Michael A. , Barr Mason , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a female infant with Apert syndrome (acrocephalosyndactyly, type I) and a frontonasal encephalocele with unremarkable family history.
Osteoporosis‐pseudoglioma syndrome: Report of three affected sibs and an overview
Authors: Frontali Marina , Stomeo Chiara , Dallapiccola Bruno , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a sibship with one brother and two MZ twin sisters affected with osteoporosis‐pseudoglioma syndrome. An analysis of the present and literature data showed that vitreoretinal dysplasia or phthisis bulbi and X‐ray evidence of osteoporosis must be considered minimal diagnostic criteria. Mental retardation, ligamentous laxity, and other reported anomalies are highly variable manifestations in the syndrome. Segregation analysis confirmed autosomal recessive transmission. The geographic origin of reported families suggests a higher gene frequency in Mediterranean countries.