bluuebunny/crossref_metadata_2025 huggingface dataset:
Cincinnati myocardial infarction and hormone family study: Family resemblance for testosterone in random and MI families
Authors: Rice Treva , Sprecher Dennis L. , Borecki Ingrid B. , Mitchell Laura E. , Laskarzewski Peter M. , Rao D. C.
Published: June 2005

Familial correlations for total testosterone and free testosterone were examined in both random and nonrandom families participating in the Cincinnati Myocardial Infarction and Hormone Family Study (CIMIH). The nonrandom families were ascertained through Caucasian males who had survived a myocardial infarction (MI) prior to age 56 years, while random families were recruited largely through an adolescent boy maturation study. Eight sex‐specific familial correlations were estimated (father‐mother, father‐son, father‐daughter, mother‐son, mother‐daughter, son‐son, daughter‐daughter, and son‐daughter) for each of the MI and random samples using maximum likelihood methods with appropriate ascertainment correction. These familial correlations were examined for differences between the random and MI samples, as well as for sex‐specific familial patterns. The results suggest that total testosterone levels may have a limited role in determinig MI risk, as evidenced by the overall heterogeneity between samples, and lower serum levels in MI than random probands. The pattern of correlations for both androgens suggests that a simple genetic model appears unlikely; however, familiality connot be ruled out. Although possible covariate effects such as age and sex may have masked some potentially significant results, especially in males, familiality in females is suggested (correlations ranging from .3–.9) The relative stability of these hormones in females as compared to that in males may have contributed to its identification, and suggests the familial transmissibility may be associated with adrenal production and/or metabolic clearance of testosterone. © 1993 Wiley‐Liss, Inc.
Growth pattern in the Apert syndrome
Authors: Cohen M. Michael , Kreiborg Sven
Published: June 2005

In this paper, we demonstrate that a discernible and unique growth pattern characterizes the Apert syndrome. The keys to understanding Apert newborn measurement values are brain size and cranial configuration. Both true megalencephaly and coronal synostosis are present at birth. Thus, the head is unusually heavy and the cranium is disproportionately high. Mean newborn length and weight are above the normal 50th centile. Of our newborn patients, 16% exceeded 4,000 g in weight. Preterm infants were appropriate or slightly large for gestational age. A biphasic linear growth pattern was found. In childhood, deceleration of linear growth occurs so that most values fall between the 5th and 50th centiles. From adolescence to adulthood, deceleration becomes more pronounced. This 2‐step linear growth deceleration results in large measure from rhizomelic shortness of the lower limbs. Puberty takes place within the normal time frame. Although a disproportionate amount of the megalencephaly accounts for the dramatic increase in head height, the widely patent midline calvarial de fect, allowing the brain to expand anteriorly into the metopic area, and some increase in the head breadth permit the mean head circumference at birth to normalize slightly above the 50th centile. During the growth period, the head circumference was studied in surgically unoperated Apert patients from the 1960s and earlier. The natural history of the growing cranium consists of gradual deceleration in head circumference from slightly above the 50th centile at birth to within or at −2 SD later on. © 1993 Wiley‐Liss, Inc.
Proteus syndrome: Clinical evidence for somatic mosaicism and selective review
Authors: Cohen M. Michael
Published: June 2005

I report 2 unusual cases of Proteus syndrome that support the concept of somatic mosaicism. In one patient, a huge connective tissue nevus covered the chest and abdomen and hyperostoses of the calvaria were observed. In the other patient, linear verrucous epidermal nevi, epibulbar dermoids, and hyperostoses were found. No enlargement of the limbs or digits occurred and the plantar surfaces of the feet were normal. Selective aspects of Proteus syndrome not previously reviewed are also presented including: uncommon neoplasms; pulmonary and renal abnormalities; brain malformations; facial phenotype associated with seizures and severe mental deficiency; and types of abnormal growth in the craniofacial skeleton. © 1993 Wiley‐Liss, Inc.
Johnson–McMillin syndrome: Report of another family
Authors: Hennekam Raoul C. M. , Holtus Frank J. A. M.
Published: June 2005

We describe a mother and son with facial nerve palsy, multiple truncal café‐au‐lait spots, and mild developmental delay. The mother also had hyposmia, increased tendency to caries, and growth retardation, and the son hypotrichosis, hearing loss, and microtia. This apparently autosomal dominant disorder was described first by Johnson et al. [1983: Am J Med Genet 15:497–506] and Johnston et al. [1987: Am J Med Genet 26:925–927]. © 1993 Wiley‐Liss, Inc.
Provisionally unique autosomal recessive chondrodysplasia punctata syndrome
Authors: Toriello Helga V. , Higgins James V. , Miller Theodore
Published: June 2005

Stippled epiphyses occur in several monogenie, teratogenic, or aneuploidy syndromes. We describe two sibs with a provisionally unique chondrodysplasia punctata syndrome, who have, in addition to stippled epiphyses, minor facial anomalies, short stature, and ocular colobomata. Inheritance of this condition is likely autosomal recessive. © 1993 Wiley‐Liss, Inc.
PHAVER syndrome: An autosomal recessive syndrome of limb pterygia, congenital heart anomalies, vertebral defects, ear anomalies, and radial defects
Authors: Powell Cynthia M. , Chandra Roma S. , Saal Howard M.
Published: June 2005

We have studied 2 sibs with vertebral, radial, congenital heart, and ear defects. The second patient also had limb pterygia and meningomyelocele. The abnormalities in these two sibs are seen in the VATER association; however, distinguishing these cases from the VATER association are the findings of pterygia, meningomyelocele, and probable autosomal recessive inheritance. We propose the acronym PHAVER syndrome for limb pterygia, heart defects, autosomal recessive inheritance, vertebral defects, ear anomalies and radial defects. This represents an new autosomal recessive disorder with phenotypic variability. © 1993 Wiley‐Liss, Inc.
Tetrasomy 9p: Tissue‐limited idic(9p) in a child with mild manifestations and a normal CVS result. Report and review
Authors: Grass Frank S. , Parke James C. , Kirkman Henry N. , Christensen Vicky , Roddey O. F. , Wade Ronald V. , Knuston Cam , Spence J. Edward
Published: June 2005

Supernumerary isochromosomes resulting in autosomal tetrasomy are rare and have been described only for 12p, 18p, and 9p. Nineteen previous cases of tetrasomy 9p have been reported, and in 6 cases, tissue‐specific mosaicism was implied with the i(9p) cell line present exclusively or predominantly in blood. We report on an infant who had apparently normal chromosomes (46,XY) on CVS. He was referred for genetic evaluation because of mild developmental delay and minor anomalies. In 75% of blood cells he had an extra isodicentric 9p chromosome (pter→q12→pter). The interpretation of tetrasomy 9p was confirmed by elevated GALT activity. No tetrasomy 9p cells were seen in 100 skin fibroblasts. This case demonstrates the tissue specific mosaicism in tetrasomy 9p which rendered the anomaly undetectable by CVS. It also demonstrates the mild end of the clinical spectrum associated with tetrasomy 9p. © 1993 Wiley‐Liss, Inc.
Combined enzymatic and linkage analysis for heterozygote detection in Hunter syndrome: Identification of an apparent case of germinal mosaicism
Authors: Simon‐Schiff Elena Ben , Bach Gideon , Zlotogora Joël , Abeliovich Dvorah
Published: June 2005

Hunter syndrome is an X‐linked recessive disorder. Determination of heterozygotes is of vital importance in genetic counselling. We describe the DNA linkage analysis in 6 Hunter syndrome families and compare it to previous results based on a serum assay for IDS activity. Our results confirm the reliability of the serum assay. The serum test correctly detected 11/12 of the 1st degree relatives tested by the serum assay (6/7 carriers and 5/5 non‐carriers). The only case with an apparent false negative result in the serum test was a daughter of a “probable heterozygote” whose serum test was also negative. We suggest that in this family the mother represented a case of germinal mosaicism and her daughter, based on the serum test, was not a carrier. If our interpretation is correct, then the apparent false negative results were correct.

It is concluded that in families where the mutation is not known and DNA analysis is not possible due to the lack of informative RFLPs or due to the lack of DNA samples on key individuals, as well as in sporadic cases, the serum test should be applied as an alternative option for heterozygote detection. © 1993 Wiley‐Liss, Inc.
de Lange syndrome: A clinical review of 310 individuals
Authors: Jackson L. , Kline A. D. , Barr M. A. , Koch S.
Published: June 2005

Three hundred ten individuals with a clinical diagnosis of de Lange syndrome were seen and examined in conjunction with the parent support group. One hundred thirty‐four males and 176 females whose ages ranged from birth to 37 years made up the study group. Examination findings were recorded for those features described by de Lange in her original report of the syndrome to determine the frequency and significance of each. In addition, questionnaires were completed by 128 of these families and medical, growth and developmental records were collected. The clinical diagnosis seems best supported by the facial features of the syndrome including the long eyelashes and confluent eyebrows (synophrys), although additional characteristics are needed. Only 27% had the upper limb deficiencies commonly associated with the syndrome. Growth was retarded in nearly all individuals, often of prenatal onset. Medical problems occurred frequently and most often involved the eye and ear, as well as the cardiac and gastrointestinal systems. Of 14 deaths, almost half were secondary to cardiac or gastrointestinal complications. The recurrence risk in 377 sibs of the patients was calculated to be less than 1%. Although development lagged significantly in speech, most individuals developed good self‐help skills. The study demonstrated a higher proportion of patients affected mildly with the syndrome than is commonly appreciated. This underscores the importance of early recognition and appropriate medical and developmental support. © 1993 Wiley‐Liss, Inc.
Brachmann‐de Lange syndrome. Delineation of the clinical phenotype
Authors: Ireland M. , Donnai D. , Burn J.
Published: June 2005

A total of 31 cases previously diagnosed as having Brachmann‐de Lange syndrome were ascertained and examined, of which 11 were thought to have been misdiagnosed. Of those correctly diagnosed, there appeared to be a phenotypic dichotomy with classical and mild cases. Those facial findings of greatest diagnostic value were the combination of the characteristic eyebrows, long philtrum, thin lips and crescent‐shaped mouth. The characteristic eyebrows were neat, well defined and arched as though they had been pencilled. This combination of anomalies was absent in postpubertal males but not in postpubertal females. Facial abnormalities most likely to lead to incorrect use of the eponym were hypertrichosis, synophrys, and bushy eyebrows. © 1993 Wiley‐Liss, Inc.
Metacarpophalangeal pattern profile analysis in Brachmann‐de Lange syndrome
Authors: Butler Merlin G. , Dahir George A. , Gale David D. , Meaney F. John
Published: June 2005

We analyzed the metacarpophalangeal pattern profile (MCPP) of 19 individuals with Brachmann‐de Lange syndrome (BDLS) and calculated a mean syndrome profile. Fourteen of 19 individuals with BDLS had significant positive correlations which indicated clinical homogeneity. Discriminant analysis of individuals with BDLS compared with a sample of normal individuals produced a correct classification rate of 100% based on a function of 2 MCPP variables that may provide a useful tool for assisting in the diagnosis of BDLS. An average pattern variability index calculated for the BDLS patients was 1.9 indicating an abnormal hand pattern in this syndrome. © 1993 Wiley‐Liss, Inc.
Prenatal diagnosis of congenital diaphragmatic hernia not amenable to prenatal or neonatal repair: Brachmann‐de Lange syndrome
Authors: Jelsema Russel D. , Isada Nelson B. , Kazzi Nadya J. , Sargent Kate , Harrison Michael R. , Johnson Mark P. , Evans Mark I.
Published: June 2005

Brachmann‐de Lange syndrome (BDLS) is a variable multiple congenital anomaly syndrome that occasionally includes congenital diaphragmatic hernia (CDH). CDH per se is commonly diagnosed antenatally and has been corrected with increasing success in utero and by neonatal repair with extracorporeal membrane oxygenation (ECMO). In utero repair requires normal karyotype as well as the absence of other lethal anomalies. Postnatal repair in combination with ECMO has resulted in improved neonatal outcome and has been recommended in all cases not having in utero repair. We describe a fetus diagnosed with a diaphragmatic hernia at 18 weeks of gestation in a woman whose only other pregnancy has been a 16 week abortus diagnosed with Fryns syndrome (FS). FS is a lethal, variable congenital anomaly syndrome that includes CDH, which is thought to contribute to the lethality of the syndrome. In utero repair was considered, but rejected because of the position of the liver and suspected FS. The Patients elected to carry the pregnancy to term. Postnatal repair with ECMO was considered; however, the infant died at several hours of age because of severe pulmonary hypoplasia, being considered ineligible for ECMO. The diagnosis of BDLS was made at autopsy and suggests that the first case may, in fact, have been BDLS. In spite of recent success in the repair of CDH both in et ex utero, CDH in association with BDLS is likely lethal, and women with fetuses diagnosed antenatally with CDH and BDLS should be counseled as such. © 1993 Wiley‐Liss, Inc.
Fetal biometry in the Brachmann‐de Lange syndrome
Authors: Kliewer Mark A. , Kahler Stephen G. , Hertzberg Barbara S. , Bowie James D.
Published: June 2005

The Brachmann‐de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross‐sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley‐Liss, Inc.
Survey of speech and language skills with prognostic indicators in 116 patients with Cornelia de Lange syndrome
Authors: Goodban Marjorie T.
Published: June 2005

Speech and language evaluations of 116 patients, ages 2 months to 29 years, with Cornelia de Lange syndrome (CdLS), also known as Brachmann‐de Lange syndrome, were conducted to survey speech and language skills and to ascertain the prognostic value of related variables. These patients were evaluated at conferences of the CdLS Foundation. The data from these evaluations were then analyzed using the database program of Paradox 3.5. The findings indicated that 53% of the children who were 4 years or older combined 2 or more words into sentences and 33% had no words or only 1–2 words. Four percent were judged to have language skills within normal to low‐normal limits. Children who were not talking at all or who were severely delayed in language skills had at least one of the following characteristics: birth weight under 5 lbs.; a reported diagnosis of moderate‐to‐severe hearing impairment; upper limb malformations; poor abilities to related socially; and/or severe motor delays, e.g., they did not sit up until after age 25 months or did not walk until after 35 months. © 1993 Wiley‐Liss, Inc.
Lethal bone dysplasia in a fetus with manifestations of atelosteogenesis I and Boomerang dysplasia
Authors: Greally Marie T. , Jewett Tamison , Smith Wilbur L. , Penick George D. , Williamson Roger A.
Published: June 2005

Atelosteogenesis I (AT‐I) and Boomerang dysplasia have been described as separate lethal bone dysplasias. The possibility of a common cause of both conditions was suggested by Hunter and Carpenter (Clin Genet 39(6): 471–480, 1991) in their report of a patient with apparent manifestations of both AT‐I and Boomerang dysplasia. We report on a male fetus of 31 weeks gestation whose clinical, radiologic and histologic findings are compared to reported cases of AT‐I, Boomerang dysplasia and the patient of Hunter and Carpenter (Clin Genet 39(6): 471–480, 1991). From the documentation of clinical and radiologic findings we demonstrate overlap of AT‐I and Boomerang dysplasia in our patient, and, from histologic examination, suggest a defect of cartilage and bone formation as the basic abnormality in this lethal bone dysplasia. © 1993 Wiley‐Liss, Inc.
Limb deficiencies, chorion villus sampling, and advanced maternal age
Authors: Halliday Jane , Lumley Judith , Sheffield Leslie J. , Lancaster Paul A. L.
Published: June 2005

Record linkage between a prenatal diagnosis register and a congenital malformation register in the state of Victoria, Australia, has enabled further evaluation of the suggested association between limb deficiencies and early chorion villus sampling (CVS). We found 3 anomalies in this category after later CVS (i.e., 9 weeks and beyond), but our data suggest that advanced maternal age may be a risk factor for both terminal and all limb deficiencies.

The data from Victoria are tabulated with data obtained from other registers. Different birth prevalence figures are obtained by different registers, therefore limiting comparisons between registers. © 1993 Wiley‐Liss, Inc.
Najjar syndrome revisited
Authors: Thomas I. T. , Jewett T. , Lantz P. , Covitz W. , Garber P. , Berry M. N.
Published: June 2005

We describe 2 brothers with cardiomyopathy and hypergonadotropic hypogonadism and conclude that this is the first description of the Najjar syndrome in the United States. The inheritance may be autosomal recessive. © 1993 Wiley‐Liss, Inc.
Prenatal diagnosis and clinical findings in a case of hexasomy 12p
Authors: van Den Veyver Ignatia B. , Macha Michelle E. , McCaskill Christopher , Carpenter Robert J. , Shaffer Lisa G.
Published: June 2005

We report the first case of hexasomy 12p mosaicism due to 2 copies of an apparent i(12p) [46,XX/48,XX, +i(12p),+i(12p)] In every cell that contained the i(12p), 2 copies of the marker were found. The hexasomy was found in amniocytes (16%) and skin fibroblasts (95%) but not in peripheral blood lymphocytes. The chromosomal origin of the marker was confirmed with the use of in situ hybridization of alpha‐satellite specific for the centromere of chromosome 12. The present case was diagnosed following chromosome analysis for anomalies on ultrasound. The hexasomy 12p patient showed striking phenotypic similarities with severely affected tetrasomy 12p cases and died shortly after birth. We propose that the more severe presentation of this case is due to the 4 extra copies of 12p. © 1993 Wiley‐Liss, Inc.
Assocition between “plagiocephaly” and hemifacial microsomia
Authors: Padwa Bonnie L. , Bruneteau Richard J. , Mulliken John B.
Published: June 2005

Fifteen of 155 patients with hemifcial microsomia were noted to have frontal plagiocephaly. These patients were examined to determine whether the frontal flattening was either secondary to deformation, the result of unilateral coronal synostosis, or part of the spectrum of hemifacial microsomia. The patients were categorized as having deformational versus synostotic frontal plagiocephaly by documenting position of the supraorbital rims, nasal root, ears, malar eminences, chin point, and the palperbral fissure height. Other extracraniofacial anomalies were also noted. Fourteen of 15(93%) patients had characteristic deformational abnormalities. Only 1/15(7%) had an elevated orbit, suggestive of unilateral coronal synostosis, but theis diagnosis was not radiographically confirmed. Frontal deformational plagiocephaly was ipsilateral to the side predominantly affreted by hemifacial microsomia in all but on e patient. Patients with hemifacial microsomia‐deformational frontal plagiocephaly often had ipsilateral torticollis, cervical spine abnormalities, and anomalies outside the craniofacial region. This was in contrast to patients with deformational frontal plagiocephaly, in the absence of hemifacial microsomia, who frequently had ipsilateral torticollis but no other anomalies. This study also undrscores possible confusion in defferentiating hemifacial microsomia from deformaional hemifacial hypoplasia on physical exaination. The association of deformational frontal plagiocephaly and hemifacial microsomia belies a rigid etiologic label of deformational versus malformative anomaly. © 1993 Wiley‐Liss, Inc.
Prenatal testing in a fetus at risk for autosomal dominant polycystic kidney disese and autosomal recessive junctional epidermolysis bullosa with pyloric atresia
Authors: Turco Alberto E. , Peissel Bernard , Rossetti Sandro , Selicorni Angelo , Manoukian Siranoush , Brusasco Alberto , Tadini Gianluca , Galimberti Andrea , Tassis Beatrice , Turolla Licia , Tenconi Romano , Pignatti Pier Franco
Published: June 2005

Amniocentesis and fetal skin biopsies were performed at 18 weeks of gestation in a fetus at risk autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive junctional epidermolysis bullosa (EBJ) with pyloric atresia. A previous son of the couple under investigation had disd at 3 months of EBJ. The mother of the propositus has ADPKD. Genetic linkage studies were carried out in 11 relatives (4 with ADPKD), and on fetal DNA obtained from cultured amniocytes, using 8 flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and a DNA marker linked to another putative ADPKD locus on chromosome 2p. The linkage results indicated that the fetus had not inherited the ADPKD chromosome from the affected mother, with a diagnostic accuracy of >99%. Ultrastructural and immunohistochemical analyses of multiple fetal skin biopsies showed no EBJ‐associated abnormalities. Thus, combining recent morphological and molecular diagnostic methods, we could show that the fetus was free from both diseases. After 40 weeks of gestation, a normal male infant was delivered. © 1993 Wiley‐Liss, Inc.
Schizophrenia: Genetics and the maternal immune response to viral infection
Authors: Wright Padraig , Gill Michael , Murray Robin M.
Published: June 2005

Thirty years ago, Eliot Slater suggested that the reason schizophrenia was not progressively eliminated from the population was that the responsible gene also conveyed a compensatory advantage in terms of increased resistance to infection. If this selective advantage lies in the antibody response to certain viral infections, this could explain recent studies suggesting that exposure to influenza in the second trimester of gestation increases the risk of later schizophrenia. We propose that prenatal exposure to influenza induces maternal antibodies which then cross‐react with proteins in the developing foetal brain, becoming foetal autoantibodies. Thus an immunogenetic response by the mother results in aberrant foetal neurodevelopment, the biological substrate for a proportion of adult schizophrenia. Initial research strategies to test this hypothesis are proposed. © 1993 Wiley‐Liss, Inc.
Usefulness of twin studies for exploring the etiology of childhood and adolescent psychiatric disorders
Authors: LaBuda Michele C. , Gottesman I. I. , Pauls David L.
Published: June 2005

It is estimated that approximately 12% of the individuals under the age of 18 in the United States have a diagnosable mental illness [Institute of Medicine, 1989]; however, only a minority of the etiological research in psychopathology focuses on disorders with childhood onset. The present report demonstrates the usefulness of twin studies in exploring the etiology of childhood and adolescent psychiatric psychopathology and reviews the design, methodology, and results from traditional twin studies of various behavioral disorders. Alternative twin designs are also reviewed in an effort to address the future direction of twin studies in the area of childhood and adolescent psychopathology and to illustrate that twin data have much more to offer the field of psychopathology than merely an initial test to rule in or to rule out a significant genetic contribution to the development of such behaviors. © 1993 Wiley‐Liss, Inc.
Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: Probable effects of family history of schizophrenia?
Authors: Nimgaonkar V. L. , Zhang X. R. , Caldwell J. G. , Ganguli R. , Chakravarti A.
Published: June 2005

Using a case‐control design, a reported association of schizophrenia with homozygosity at the dopamine D3 receptor gene locus was investigated in a group of patients (n = 53), with schizophrenia (DSM‐III‐R), and psychiatrically normal controls (n = 61), matched for ethnicity and area of residence. No significant differences in the distribution of alleles or genotypes between the two groups could be deteched. However, among patients with a family history of schizophrenia, as compared to controls without such family history, an association with allele 1 at this locus was noted (Odds ratio 12.4, C.I. 1.61, 96.35). © 1993 Wiley‐Liss, Inc.
Survival in trisomy 18
Authors: Root Susan , Carey John C.
Published: June 2005

Prenatal diagnosis of trisomy 18 by amniocentesis in the latter half of pregnancy is now a common event. Accurate prognostic information is crucial for families making decisions about delivery management. Three recently published studies showed much shorter survival for trisomy 18 than was reported by earlier papers. For this reason, we studied trisomy 18 survival. We examined chromosome laboratory records to find all trisomy 18 diagnoses made in Utah between 1979 and 1988. Death certificates and hospital records were used to determine survival. We found 64 live‐born cases with trisomy 18 out of 388,563 total births over the 10‐year period, a prevalence of 1/6071. Our results show a median survival of 4 days and a 1 week survival of 45%, similar to that reported in the 3 recent studies. However, we had a significantly greater survival at 6 months (9% in Utah versus 3% in Denmark) and 1 year (5% versus 0 in the 3 studies). In contrast to recent studies, earlier investigations showed 80% survival at 2 weeks and 8% at 1 year. It is not surprising that recent studies show shorter survival, since in the 1960s the diagnosis was typically not made until age 2 months. With prenatal and neonatal diagnosis many cases which would have died prior to detection in earlier times are now diagnosed. The longer survival discrepancies are more difficult to explain, but may simply be due to small numbers. © 1994 Wiley‐Liss, Inc.
Familial hydrocephalus of prenatal onset
Authors: Zlotogora Joël , Sagi Michal , Cohen Tirza
Published: June 2005

Fourteen families in which more than one child was diagnosed with hydrocephalus of prenatal onset were seen in our genetic counseling clinic. In 7 families only males were affected: in 2 X‐linked hydrocephalus was diagnosed while X‐linked inheritance was suspected in 3 other families. These 5 families were of Jewish origin. In the 8 families of Arab origin, the parents of the affected children were consanguineous. In 6 of these families at least one female was affected and the hydrocephalus was most probably inherited as an autosomal recessive trait. This type of hydrocephalus of prenatal onset appears to be frequent among Palestinian Arabs. © 1994 Wiley‐Liss, Inc.
Bilateral femoral hypoplasia associated with Rokitansky sequence: Another example of a mesodermal malformation spectrum?
Authors: Bau Claiton H. D. , Ribeiro Cyntia A. , Ribeiro Schuber A. , Flores Renato Z.
Published: June 2005

We report on a woman with bilateral femoral hypoplasia and Rokitansky sequence, malformations that up to now had not been described together. There are no other cases in the family, and no history of prenatal teratogen exposure. This case may be part of a mesodermal malformation spectrum. © 1994 Wiley‐Liss, Inc.
Autosomal recessive colobomatous microphthalmia
Authors: Zlotogora Joël , Legum Cyril , Raz Judith , Merin Saul , Benezra David
Published: June 2005

Colobomatous microphthalmia was studied in multiple relatives of 5 families. In these families, the disorder was an autosomal recessive trait as opposed to the usual autosomal dominant form of the disorder. A relatively high incidence of this recessive allele is found in the Iranian Jewish community. © 1994 Wiley‐Liss, Inc.
Parental consanguinity in two sibs with omodysplasia
Authors: Baxová A. , Maroteaux P. , Barošová J. , Netriová I.
Published: June 2005

Two sibs with omodysplasia were born to phenotypically normal but consanguineous parents. They had severe micromelic dwarfism, facial anomalies, and mental retardation. One had a congenital heart defect. The radiographic findings are typical: hypoplastic distal end of the humerus with radioulnar diastasis. Parental consanguinity and clinical manifestations in 2 sibs suggest autosomal recessive inheritance. © 1994 Wiley‐Liss, Inc.
Familial 10p trisomy resulting from a maternal pericentric inversion
Authors: Kozma Chahira , Meck Jeanne M.
Published: June 2005

We report a familial recombination of a pericentric inversion of chromosome 10 resulting in 2 affected relatives who had 10p trisomy and 10q monosomy with the karyotypic abnormality designated rec(10) dup p,inv(10) (p11.2q26). Both of these individuals had the typical characteristics of 10p trisomy, however, at birth the proposita had mild facial anomalies suggesting that the distinct facial characteristics may be of postnatal onset in some cases. In addition, the proposita had gastroesophageal reflux causing severe anemia. The phenotype of our patients is compared to 41 patients with 10p trisomy reported in the literature. © 1994 Wiley‐Liss, Inc.
Additional case of opsismodysplasia supporting autosomal recessive inheritance
Authors: Beemer Frits A. , Kozlowski Kazimierz S.
Published: June 2005

The authors describe clinical and radiological findings in a 2‐year‐old boy from consanguineous parents. A diagnosis of opsi(s)modysplasia (=delayed maturation) had been made (MIM 258480). The purpose of this paper is to draw attention to the striking radiological manifestations. Consanguinity in the parents of our case and occurrence in a brother and sister in a previous report support an autosomal recessive transmission. © 1994 Wiley‐Liss, Inc.
Excess functional copy of allele at chromosomal region 11p15 may cause Widemann‐Beckwith (EMG) syndrome
Authors: Kubota Takeo , Saitoh Shinji , Matsumoto Tadashi , Narahara Kouji , Fukushima Yoshimitsu , Jinno Yoshihiro , Niikawa Norio
Published: June 2005

Wiedemann‐Beckwith syndrome (WBS) is a genetic disorder with overgrowth and predisposition to Wilms' tumor. The putative locus of the gene responsible for this syndrome is assigned to chromosome region 11p15.5, and genomic imprinting in this region has been proposed: the paternally derived gene(s) at 11p15.5 is selectively expressed, while the maternally transmitted gene(s) is inactive. We examined 18 patients for the parental origin of their 11p15 regions. DNA polymorphism analyses using 6 loci on chromosome 11 showed that 2 patients with duplications of 11p15 regions from their respective fathers and one from the mother, indicating the transmission of an excessive paternal gene at 11p15 to each patient. Our results, together with the previous findings in karyotypically normal or abnormal patients and in overgrowth mouse experiments, are consistent with imprinting hypothesis that overexpression of paternally derived gene(s) at 11p15.5, probably the human insulin‐like growth factor II (IGF‐II) gene, may cause the phenotype. Total constitutional uniparental paternal disomy (UPD) or segmental UPD for the 6 loci examined of chromosome 11 was not observed in our 12 sporadic patients. In order to explain completely the inheritance of this syndrome in patients with various chromosomal constitutions, we propose an alternative imprinting mechanism involving the other locus that may be paternally imprinted and may suppress the expression of this gene. © 1994 Wiley‐Liss, Inc.
U‐type exchange in a paracentric inversion as a possible mechanism of origin of an inverted tandem duplication of chromosome 8
Authors: Mitchell John J. , Vekemans Michel , Luscombe Sandra , Hayden Michael , Weber Bernard , Richter Andrea , Sparkes Robert , Kojis Tracy , Watters Gordon , Der Kaloustian Vazken M.
Published: June 2005

A mentally retarded male with dysmorphic features was found to have a de novo 46,XY,inv dup(8) (p.23.1 → 12). Confirmation of the segments duplicated in the rearrangement was achieved by biochemical analysis of glutathione reductase, which maps to 8p21.1, and DNA studies using the chromosome specific probe y‐19‐1D (D85131), which maps to 8p21. Assay of cathepsin B, which has been localised to 8p22, did not differ from controls with normal chromosomal constitution. DNA studies using the Defensin 1 gene probe, which maps to 8p23, showed a previously undetected deletion of that segment. We propose that the inverted tandem duplication/deletion arose as a single U‐type exchange within an inversion loop. © 1994 Wiley‐Liss, Inc.
Case of 46,XX/47,XY, + 21 chimerism in a newborn infant with ambiguous genitalia
Authors: Sawai Tomoko , Yoshimoto Masaaki , Kinoshita Ei‐Ichi , Baba Tsuneyoshi , Matsumoto Tadashi , Tsuji Yoshiro , Fukuda Shinpei , Harada Naoki , Niikawa Norio
Published: June 2005

We describe whole‐body chimerism in a newborn infant with small phallus, pseudo‐vaginal perineal hypospadias, and a bifid scrotum containing gonads. The human testis determining factor gene (SRY) was detected by PCR amplification. GTG‐banding chromosome analysis in peripheral blood lymphocytes and cultured fibroblasts derived from right cubital skin showed a 46,XX/47,XY, + 21 karyotype. Their ratios in each cell line were 294:5 and 178:7, respectively. QFQ‐banding chromosome analysis documented 3 heteromorphic statellites on trisomic chromosomes 21 in the 47,XY, + 21 cell line and a homozygous statellite pattern in the 46,XX cell line. Heteromorphic patterns of chromosomes 4, 13, 14, and 22 were also different between the two cell lines. To our knowledge, such disomy/trisomy chimeras have not been described previously. © 1994 Wiley‐Liss, Inc.
Clinical diagnosis of the Usher syndromes
Authors: Smith R. J. H. , Berlin C. I. , Hejtmancik J. F. , Keats B. J. B. , Kimberling W. J. , Lewis R. A. , Möller C. G. , Pelias M. Z. , Tranebjærǵ L.
Published: June 2005

The Usher syndromes are genetically distinct disorders which share specific phenotypic characteristics. This paper describes a set of clinical criteria recommended for the diagnosis of Usher syndrome type I and Usher syndrome type II. These criteria have been adopted by the Usher Syndrome Consortium and are used in studies reported by members of this Consortium. © 1994 Wiley‐Liss, Inc.
Ataxia, mental deterioration, epilepsy in a family with dominant enamel hypoplasia: A variant of Kohlschütter‐Tönz syndrome?
Authors: Guazzi Giancarlo , Palmeri Silvia , Malandrini Alessandro , Ciacci Giuseppe , Perri Raoul Di , Mancini Grazia , Messina Corrado , Salvadori Claudio
Published: June 2005

We describe 3 sibs, their father, and paternal grandfather with amelogenesis imperfecta. In 2 sibs and the father the defect is associated with a neurological syndrome which has a wide range of phenotypic variability. The proposita has ataxia, EEG abnormalities, moderate dementia, and enamel hypoplasia. This case and the affected relatives are discussed in relation to Kohlschütter‐Tönz syndrome and neuroectodermal diseases. The syndrome described here, characterized by the association of a genetic enamel defect and neurological impairment, may be of considerable interest in advancing genetic and clinical knowledge on ectodermal tissues and their development. © 1994 Wiley‐Liss, Inc.
Congenital hypoplastic anemia: Another example of autosomal dominant transmission
Authors: Gojic V. , Van't Veer‐Korthof E. T. , Bosch L. J. , Puyn W. H. , van Haeringen A.
Published: June 2005

Congenital hypoplastic anemia (CHA) or Blackfan‐Diamond anemia (BDA) is a rare congenital abnormality of erythropoiesis characterized by normochromic, macrocytic anemia presenting in infancy or early childhood. Associated phenotypic abnormalities such as triphalangeal thumbs and cleft lip and/or palate are found in 70% of cases. Although most cases are sporadic, several reports suggest either autosomal dominant or autosomal recessive inheritance. We report on a 3 generation family with autosomal dominant inheritance of CHA. © 1994 Wiley‐Liss, Inc.
Wisconsin Stillbirth Service Program: I. Establishment and assessment of a community‐based program for etiologic investigation of intrauterine deaths
Authors: Pauli Richard M. , Reiser Catherine A. , Lebovitz Ruth M. , Kirkpatrick Susan J.
Published: June 2005

Although stillbirth is a common event, few programs have previously been established for the comprehensive etiologic investigation of intrauterine death. Fewer still have been prospective, unbiased in ascertainment, and consistent in protocol utilization. The Wisconsin Stillbirth Service Program was established in 1983 as a unique model for the investigation of the causes of stillbirth. This community‐based, University‐supported model for health care delivery is here described. Through it more than a thousand infants have been etiologically investigated. We demonstrate that a community‐based program of stillbirth assessment can succeed, that compliance with recommended protocols is high and that a specific primary cause of fetal death can be demonstrated in about 40% of referrals. A majority of the established causes of intrauterine death are fetal etiologies. Furthermore, it appears that there are no substantial referral biases. Lack of such biases, together with the prospective, protocol driven nature of the program provides a unique population upon which to base estimates of the frequency of various etiologic diagnoses and classes and categories of cause. © 1994 Wiley‐Liss, Inc.
Wisconsin Stillbirth Service Program: II. Analysis of diagnoses and diagnostic categories in the first 1,000 referrals
Authors: Pauli Richard M. , Reiser Catherine A.
Published: June 2005

The Wisconsin Stillbirth Service Program has provided a mechanism for the collection and analysis of unbiased and representative information concerning stillborn infants. Generated diagnoses and diagnostic categories within the first 1,000 referrals (including 789 stillbirths) is summarized here. Among all referred stillborns, 24.5% were found to have an identifiable intrinsic fetal cause of death. Specific diagnoses were extraordinarily heterogeneous, with about 85 different processes identified with this group. No single diagnosis was found in more than 1 1/2% of the evaluated stillborns. Distribution by classes of fetal causes (as a percent of all fetal causes in stillborns) included malformation syndromes in 44%, single malformations and defined sequences in 34%, disruptions in 10%, and dysplasias in 3%. The heterogeneity of syndromic causes is illustrated, examples of previously undescribed syndromic processes provided and the problems experienced in generating specific diagnoses discussed. Specific single malformations, sequences, disruptions, and dysplasias are also tabulated and illustrated. Distribution by etiologic categories (as a percent of all fetal causes in stillborns) included defined sporadic conditions in 29%, cytogenetic aberration in 25%, presumed multifactorial processes in 12%, Mendelian disorders in 5%, and environmental events in less than 4%. A fourth of all fetal causes could not be sufficiently defined to allow for certainty in assigning a specific etiologic category. The materials summarized provide reference data regarding the frequency of classes and categories of fetal diagnoses generated from an unbiased and non‐selected series of stillborns. © 1994 Wiley‐Liss, Inc.
Oculocutaneous albinism, immunodeficiency, hematological disorders, and minor anomalies: A new autosomal recessive syndrome?
Authors: Kotzot Dieter , Richter Konrad , Gierth‐Fiebig Kornelia
Published: June 2005

We report on 2 related children, a boy and a girl, from a large Turkish clan. Their parents are both first cousins and have several common ancestors. Both children have tyrosinase‐positive oculocutaneous albinism, recurrent bacterial infections, granulocytopenia, intermittent thrombopenia, and microcephaly, a protruding midface, rough and projecting hair, and mild mental retardation. Chromosomes are normal. Metabolic disorders were excluded.

None of 14 well‐known types of albinism, including Hermansky‐Pudlak syndrome and Chediak‐Higashi syndrome, nor any other genetic syndrome, characterizes our patients sufficiently. Thus, this combination of symptoms is considered a new autosomal recessive syndrome. © 1994 Wiley‐Liss, Inc.
Emery‐Dreifuss syndrome: Genetic and clinical varieties
Authors: Rudenskaya G. E. , Ginter E. K. , Petrin A. N. , Djomina N. A.
Published: June 2005

Two familial and 2 sporadic cases of Emery‐Dreifuss syndrome are reported. One family presented a rare autosomal dominant variant of Emery‐Dreifuss muscular dystrophy, another with X‐linked recessive inheritance showed unusual intrafamilial variability. One of sporadic cases closely resembled rigid spine syndrome, the other was clinically intermediate between Emery‐Dreifuss muscular dystrophy and rigid spine syndrome, showing that they are not distinct disorders. © 1994 Wiley‐Liss, Inc.
Barth syndrome: Clinical observations and genetic linkage studies
Authors: Christodoulou J. , McInnes R. R. , Jay V. , Wilson G. , Becker L. E. , Lehotay D. C. , Platt B.‐A. , Bridge P. J. , Robinson B. H. , Clarke J. T. R.
Published: June 2005

Barth syndrome is an X‐linked recessive condition characterized by skeletal myopathy, cardiomyopathy, proportionate short stature, and recurrent neutropenia, but with normal cognitive function. Some, but not all patients, exhibit carnitine deficiency and/or the presence of 3‐methylglutaconic and ethylhydracylic acids in urine. Recently the mutation causing Barth syndrome was localised to the Xq28 region by linkage analysis. We report 6 cases of Barth syndrome from 4 families and highlight the fact that neuromuscular and cardiovascular symptoms and the severity of infections tend to improve with age, while short stature persists. Also previously unreported was myopathic facies and nasal quality to speech in our cases. The urinary organic acid abnormalities and plasma carnitine deficiency were inconsistent findings. We propose that they may be epiphenomena rather than indicators of the primary metabolic defect, and that the primary defect or defects in this disorder may lie in the mitochondrial electron transport chain. © 1994 Wiley‐Liss, Inc.
RSH/SLO (Smith‐Lemli‐Opitz) syndrome: Designing a high cholesterol diet for the SLO syndrome
Authors: Acosta Phyllis B.
Published: June 2005

A high cholesterol diet has been suggested to help prevent the poor reproductive outcomes found in heterozygote carriers of fetuses affected with the Smith–Lemli–Opitz (SLO) syndrome. The theory has also been presented that a high cholesterol medical food may enhance myelination of the central nervous system of the infant and prevent demyelination in the child and adult with SLO. Clinical studies are required to test this hypothesis and to determine the optimal composition of such medical foods. FDA requires proof of efficacy and controls nutrient composition, ingredients, and label claims of medical foods. © 1994 Wiley‐Liss, Inc.
Median nodule of the upper lip: An autosomal dominant trait
Authors: Tsukahara Masato , Fernandez Isabel , Sugio Yoshitsugu , Shiota Kohei
Published: June 2005

We describe a total of 18 individuals, in 3 families, with a median nodule of the upper lip. In family 1, the proposita, an 8‐month‐old infant girl, was otherwise phenotypically normal except for a median nodule of the upper lip. The proposita's elder brother and mother, both phenotypically normal, also had the similar nodule of the upper lip. On the mother's side, the proposita's greatgrandmother, great‐grandaunt, grandfather, greataunt, two aunts, and one female cousin all had a median nodule of the upper lip. In family 2, the proposita, proposita's mother and maternal grandfather had a median nodule of the upper lip. In family 3, the proposita, proposita's father, paternal grandfather, paternal uncle, and cousin had a median nodule of the upper lip. Analysis of 3 families indicates that the condition is an autosomal dominant trait. © 1994 Wiley‐Liss, Inc.