bluuebunny/crossref_metadata_2025 huggingface dataset:
Chorionic villus sampling followed by amniocentesis in the same pregnancy
Authors: Donnenfeld Alan E. , Librizzi Ronald J. , Dunn Linda K. , Craparo Frank , Godmilow Lynn , Weiner Stuart
Published: June 2005

In our consecutive series of 2,574 chorionic villus sampling (CVS) patients, 146 women (5.7%) underwent a subsequent amniocentesis in the same pregnancy for the indications of absent or insufficient villi (3.3%), elevated maternal serum alpha‐fetoprotein (0.93%), CVS mosaicism (0.89%), culture failure (0.23%), specimen contamination (0.15%), and CVS aneuploidy (0.12%). Patients presenting for a CVS should be informed of the possible need for a subsequent amniocentesis in the same pregnancy. There is a need for individual prenatal diagnosis programs to analyze their own data and provide genetic counseling information which pertains specifically to their institution. © 1993 Wiley‐Liss, Inc.
Genetic counselling in Noonan syndrome
Authors: Sharland Michael , Morgan Maureen , Smith Gill , Burch Michael , Patton Michael A.
Published: June 2005

A clinical and echocardiographic study is presented of 117 families with Noonan syndrome. The 117 families contained 144 individuals with typical Noonan syndrome. The age range of these individuals was from one week to 45 years (mean 12.0 years). One parent was definitely affected with Noonan syndrome in only 14% of the 117 families (mother 11%, father 3%). In a further 31% of families, one parent had possible signs of Noonan syndrome, based on facial appearance only. Within the apparently sporadic group of probands there was no evidence of increased parental age. Echocardiography demonstrated no cases of subclinical cardiac disease in all first degree relatives examined, and clinical examination alone missed no case of cardiac disease. Segregation analysis of affected pedigrees confirmed autosomal dominant inheritance. If both parents had only possible or no signs of Noonan syndrome, subsequent to the birth of the first child with Noonan syndrome in a family, an empiric recurrence risk of 5% was obtained. © 1993 Wiley‐Liss, Inc.
Dysspondylochondromatosis
Authors: Freisinger P. , Finidori G. , Maroteaux P.
Published: June 2005

We report on 3 unrelated patients with an unusual form of neonatal dwarfism with unequal limb length. Radiographs show multiple enchondromatosis of the tubular and the flat bones and severe segmentation abnormalities of the vertebral column. These observations differ from the hitherto described forms of multiple enchondromatosis with growth disorders of the spine, spondyloenchondroplasia, and others. Therefore we propose to delineate this disorder as a new entity. © 1993 Wiley‐Liss, Inc.
Otopalatodigital syndrome type II associated with omphalocele: Report of three cases
Authors: Young Katherine , Barth Christine K. , Moore Cynthia , Weaver David D.
Published: June 2005

We present 3 patients with otopalatodigital (OPD) syndrome type II and omphalocele; 2 of the cases are brothers. There are now 6 known cases of OPD type I or II with omphalocele. We propose that this combination is not co‐incidental and discuss mechanisms that may result in the combination of OPD, omphalocele, and other midline defects. © 1993 Wiley‐Liss, Inc.
Unusual lymphangioma observed prenatally in a 45,X fetus
Authors: Haeusler Martin C. H. , Ryan Greg , Sams Virginia , Robson Stephen C. , Young Martin , Sullivan Ian D. , Lipitz Shlomo , Rodeck Charles H.
Published: June 2005

We present a case of a large frontal lesion, suspected on antenatal ultrasound to be a cephalocele. The cardiac anatomy was abnormal and fetal blood sampling showed a 45,X chromosome constitution. Postmortem examination proved this to be a lymphangioma and confirmed the presence of a cardiac defect. We suggest that this lymphangioma represents an unusual manifestation of monosomy X and discuss the importance of doing chromosome analysis in the presence of such a lesion which is of similar appearance as a cephalocele. © 1993 Wiley‐Liss, Inc.
Pleiotropy in Coffin‐Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations
Authors: Hartsfield James K. , Hall Bryan D. , Grix Arthur W. , Kousseff Boris G. , Salazar Jose F. , Haufe Scott M. W.
Published: June 2005

We report on 7 patients (6 M, 1 F) with Coffin‐Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin‐Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin‐Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley‐Liss, Inc.
Fryns syndrome
Authors: Stratton Robert F. , Young Robert S. , Heiman Howard S. , Carter Jan M.
Published: June 2005

We report on a premature female infant with Fryns syndrome who had several less commonly reported anomalies. She had bilateral posterior eventration of the hemidiaphragms instead of the usual diaphragmatic defects with visceral herniation into the chest cavity. She also had a unilateral cleft lip, camptodactyly, duodenal atresia, tracheomalacia, bronchomalacia, and Tetralogy of Fallot. © 1993 Wiley‐Liss, Inc.
Familial interstitial deletion 11(p11.12p12) associated with parietal foramina, brachymicrocephaly, and mental retardation
Authors: Shaffer Lisa G. , Hecht Jacqueline T. , Ledbetter David H. , Greenberg Frank
Published: June 2005

Parietal foramina may be an isolated autosomal dominant trait or found in syndromes. We report on two related individuals who have multiple anomalies with parietal formaina and the deletion of 11(p11.12p12) due to the inheritance of a derivative chromosome 11 from an insertional translocation dir ins(13;11)(q14.1;p11.12p12). Results of initial chromosome analyses on the proposita and her maternal halfuncle were reported as normal. However, the clinical manifestations and family history suggested a chromosomal cause and cytogenetic studies were performed on the proposita's mother. A derivative chromosome 13 was initially identified and further evaluation documented a derivative 11 as the reciprocal product. This family illustrates the importance of performing chromosome studies on the normal intervening relatives in families with multiple affected individuals with mental retardation and minor anomalies as one of the two reciprocal products may be more easily detectable in a balanced carrier. Additionally, the finding of del(11)(p11.12p12) may provide a map location for a syndrome which includes parietal foramina. © 1993 Wiley‐Liss, Inc.
Age‐associated chromosome 21 loss in Down syndrome: Possible relevance to mosaicism and Alzheimer disease
Authors: Percy Maire E. , Markovic Vjerica D. , Dalton Arthur J. , McLachlan Donald R. C. , Berg Joseph M. , Rusk Ann C. M. , Somerville Martin J. , Chodakowski Barbara , Andrews David F.
Published: June 2005

We previously observed low level mosaicism (2–4% normal cells) in phytohemagglutinin‐stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the “;occult”; mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue‐specific mosaicism and “;classical”; mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer‐type dementia in DS and in the general population. © 1993 Wiley‐Liss, Inc.
Aicardi syndrome, metastatic angiosarcoma of the leg, and scalp lipoma
Authors: Tsao Chang Y. , Sommer Annemarie , Hamoudi Ala B.
Published: June 2005

An infant girl with Aicardi syndrome, scalp lipomas, and angiosarcoma of a limb is reported. The cavernous hemangioma of the leg was benign when biopsied at age 5 months but became malignant at 11 months. Angiosarcoma caused multiple distant metastases which were evident at autopsy at age 19 months. This is the first case of Aicardi syndrome associated with lipoma and metastatic angiosarcoma. © 1993 Wiley‐Liss, Inc.
Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome
Authors: Freeman S. B. , May K. M. , Pettay D. , Fernhoff P. M. , Hassold T. J.
Published: June 2005

Chromosome 15 (15q11‐q13) abnormalities cause two distinct conditions, Angelman syndrome (AS) and Prader‐Willi syndrome (PWS). We present the first case of a child with a balanced 15;15 translocation and AS in whom molecular studies were crucial in confirming a diagnosis. DNA polymorphisms demonstrated paternal uniparental disomy for chromosome 15, consistent with the diagnosis of AS. The molecular studies also showed the patient to be homozygous at all loci for which the father was heterozygous, suggesting that the structural rearrangement was an isochromosome 15q and not a Robertsonian translocation. © 1993 Wiley‐Liss, Inc.
Familial insulin resistant diabetes associated with acanthosis nigricans, polycystic ovaries, hypogonadism, pigmentary retinopathy, labyrinthine deafness, and mental retardation
Authors: Boor R. , Herwig J. , Schrezenmeir J. , Pontz B. F. , Schönberger W.
Published: June 2005

Two sibs, whose parents are first cousins, had diabetes mellitus with hyperinsulinism, insensitive insulin receptors, and acanthosis nigricans. Both patients had pigmentary retinopathy, secondary cataracts, labyrinthine deafness, mental retardation, and cerebral atrophy. They were disproportionately short with relatively broad hands and feet and slightly coarse face. The young woman had secondary amenorrhea and polycystic ovaries and the boy gynecomastia and hypergonadotrophic hypogonadism. This appears to be the second family with a new autosomal recessive disorder differing from Alström syndrome by the presence of mental retardation and absence of renal insufficiency. Impaired insulin receptor binding and polycystic ovaries are described as part of this syndrome. © 1993 Wiley‐Liss, Inc.
Severe limb abnormalities: Analysis of a cluster of five cases born during a period of 45 days
Authors: van den Anker J. N. , van Vught E. E. , Zandwijken G. R. J. , Cohen‐Overbeek T. E. , Lindhout D.
Published: June 2005

We report on 5 individuals with severe limb abnormalities born in our hospital within a period of 45 days. Detailed clinical descriptions, photographs, and radiographs are presented. Etiological evaluations included genetic background, obstetric history, invasive procedures during pregnancy, maternal infectious diseases or maternal hyperthermia, drug use before and during pregnancy, and occupational or recreational exposures of both parents. © 1993 Wiley‐Liss, Inc.
Provisionally unique syndrome of ocular and ectodermal defects in two unrelated boys
Authors: Toriello Helga V. , Lacassie Yves , Droste Patrick , Higgins James V.
Published: June 2005

We describe an apparently new syndrome in 2 unrelated boys with aplasia cutis congenita, epibulbar dermoids, postnatally appearing areas of truncal hyperpigmentation, and macrocephaly. © 1993 Wiley‐Liss, Inc.
Mosaic dup (9p) diagnosed by fluorescence in situ hybridization (FISH)
Authors: Petty Elizabeth M. , Gibson Lisa H. , Breg W. Roy , Burns Jacqueline P. , Yang‐Feng Teresa L.
Published: June 2005

We describe a girl with some manifestations of the dup (9p) syndrome. High‐resolution Giemsa‐banded karyotype of her lymphocytes documented that she was mosaic with 80% of cells being 46,XX, and 20% 46,XX,‐20, + der(20;?) (p13;?). The additional material on 20p could not be defined clearly by high‐resolution Giemsa banding, as the banding pattern appeared consistent with either distal 9p or distal 13q. In order to make a definitive cytogenetic diagnosis, we used fluorescence in situ hybridization (FISH) with a chromosome 9 specific DNA library to establish that the origin of the additional chromosomal material on chromosome 20 was from 9p. FISH used in this situation enabled us to counsel the family specifically regarding the prognosis and manifestations of distal 9p duplication. © 1993 Wiley‐Liss, Inc.
Competing stochastic models of the incubation period: An investigation of age‐at‐diagnosis of familial and sporadic retinoblastoma
Authors: Philippe P.
Published: June 2005

This study is based on the assumption that the distribution of age‐at‐diagnosis (a synonym for the incubation period) of a disease can convey information with respect to its pathogenetic mechanisms. To this end, an analysis of 3 retinobastoma (RB) international data sets was undertaken The molecular and cellular basis of RB is well understood and may serve our purpose well. RB is broken down into familial bilateral, unilateral, and sporadic unilateral form. Survival and hazard functions were computed. Several competing stochastic models (up to 9 per RB form) were fit. Each conveyed a meaningful pathogenetic mechanism. Between‐model discrimination was achieved by examining chi‐square goodness‐of‐fit values to select the best fitting model. Well‐known survival models, such as the simple exponential and the lognormal (Sartwell model) were ruled out. Age‐at‐diagnosis of familial RB proved to be best explained by 2 interfering exponentials (a diffonential function); the logistic was retained as the best adjusted model of the incubation period of sporadic cases of RB. As to familial unilaterals, both the diffonential and the logistic models fit equally well. The 3 data sets are consistent in these results, ruling out the less well‐fit competing models The results suggest the existence of 2 opposing but independent balancing internal mechanisms at the origin of familial RB. Sporadic RB appears to be due to a single host‐dependent self‐limiting cellular mechanism. Familial unilaterals which share both of these component mechanisms would involve lower retinoblast turnover rate. The cellular implications of these findings are discussed with regard to the relative importance of endogenous and exogenous induction factors in RB. It is concluded that, according to the RB form, RB occurrence results from 2 cellular interfering forces of different strength and organization. © 1993 Wiley‐Liss, Inc.
Proteus syndrome with cardiomyopathy and a myocardial mass
Authors: Shaw Christopher , Bourke John , Dixon Joanne
Published: June 2005

Proteus syndrome is and overgrowth syndrome principally affecting cutaneous and skeletal tissues, accompanied by subcutaneous hamartomas. We report on a patient with predominantly skeletal and visceral involvement, including a cardiac mass and thickening of the myocardial septum affecting cardiac conduction and contraction. © 1993 Wiley‐Liss, Inc.
Autosomal dominant preaxial deficiency, postaxial polydactyly, and hypospadias
Authors: Guttmacher Alan E.
Published: June 2005

We report on 3 individuals, a man and his son and daughter, who were born with prexial dificiencies of the hands and feet and postaxial polydactyly of the hands. Both males also had glandular hypospadias. Certain of these findings resemble those found in the hand‐foot‐genital syndrome; however, we conclude that this family has a hitherto unreported by a single gene defect of preaxial deficiencies and postaxial polydactyly in the same individual is of note. © 1993 Wiley‐Liss, Inc.
Single base mutation that substitutes glutamic acid for glycine 1021 in the COL3A1 gene and causes Ehlers–Danlos syndrome type IV
Authors: Narcisi Paolo , Wu Yuli , Tromp Gerard , Earley James J , Richards Allan J. , Pope F. Michael , Kuivaniemi Helena
Published: June 2005

The proposita described here was a 24‐year‐old woman with an acrogeric form of the Ehlers–Danlos syndrome including a massive dissecting aortic aneurysm. She was found to have a single‐base mutation that substituted glutamic acid for glycine at amino acid position 1021 in the triple‐helical domain of type III Procollagen. It is the most carboxyterminal single‐base mutation characterized to date in the COL3A1 gene. Analysis of medium and cell layer proteins from proposita's cultured skin fibroblasts showed that the mutant protein was poorly secreted, migrated more slowly on a polyacrylamide gel, and was partially unstable at +25°C to brief digestion with trypsin. © 1993 Wiley‐Liss, Inc.
Oral‐facial‐digital syndrome type I in a newborn male
Authors: Gillerot Yves , Heimann Marianne , Fourneau Catherine , Verellen‐Dumoulin Christine , Van Maldergem Lionel
Published: June 2005

We report on a newborn male, born at term with clinical manifestations of oral‐facial‐digital (OFD) syndrome type I. This syndrome is generally assumed to be inherited in an X‐linked dominant fashion with lethality in males. Therefor, liveborn males are exceptional. This liveborn ale also had Dandy‐walker malforation and polycystic kidneys.

From a general point of view, distinction between the 8 types of (OFD) syndromes described so far appears subtle and considerable overlap exists between them. In this regard, it should be noted that polycystic kidneys different from adult polycystic kidney disease both macroscopically and microscopically are a frequent manifestation of OFD I. © 1993 Wiley‐Liss, Inc.
New form of spondyloepimetaphyseal dysplasia (SEMD) in Jewish family of Iraqi Origin
Authors: Shohat M. , Lachman R. , Carmi R. , Ziv J. Bar , Rimoin D.
Published: June 2005

We report a distinct type of spondyloepimetaphyseal dysplasia seen in 2 sibs and their second cousin, characterized by early onset severe short stature, small chest, and distended abdomen. They had short neck, severe lumbar lordosis, and marked genu varum due to fibular overgrowth and joint laxity. Radiographically, the patients had platyspondyly, initially noted during the first years of life, with central hypoplasia of the vertebral bodies. At a later age, the vertebrae appear squared with mild interpedicular narrowing. The long bone changes, which at early age resemble those seen in achondroplasia, later include general metaphyseal irregularities and significant epiphyseal ossification delay. These patients present a previously undescribed form of spondyloepimetaphyseal dysplasia, most probably transmitted as an autosomal recessive tract. © 1993 Wiley‐Liss, Inc.
Cultural and psychosocial considerations in screening for thalassemia in the Southeast Asian refugee population
Authors: Nidorf Jeanne F. , Ngo Kim‐Yen
Published: June 2005

The combination of a high incidence of thalassemia and a high fertility rate in the Southeast Asian refugee population mandates effective screening programs, but unique cultural and psychosocial factors often impede optimal screening and genetic counseling. This paper identifies cultural and psychosocial barriers often associated with refugee thalassemia screening, and offers practical guidelines for remediation. © 1993 Wiley‐Liss, Inc.
Kohlschütter‐Tönz syndrome: Epilepsy, dementia, and amelogenesis imperfecta
Authors: Zlotogora Joël , Fuks Anna , Borochowitz Zvi , Tal Yoram
Published: June 2005

Kohlschütter‐Tönz syndrome is a central nervous system (CNS) degenerative disease with convulsions and mental regression in which the affected children present with yellow teeth due to defective enamel. We present a family in which 2 affected children (a boy and a girl) were born to consanguineous parents. This report confirms the autosomal recessive inheritance of the disorder. The combination of a CNS and an enamel defect may represent pleiotropy or a contiguous gene syndrome. © 1993 Wiley‐Liss, Inc.
Exclusion of the neurofibromatosis 1 locus in a family with inherited café‐au‐lait spots
Authors: Brunner Han G. , Hulsebos Theo , Steijlen Peter M. , der Kinderen Daan J. , v.d. Steen A. , Hamel Ben C. J.
Published: June 2005

We have performed linkage analysis is a small family with autosomal dominant inheritance of multiple café‐au‐lait spots (CLS) in order to clarify its relationship to classical von Recklinghausen disease (NF 1). We found that an affected woman had transmitted a different haplotype for markers flanking the NF 1 gene to both of her affected daughters. These results exclude an allelic mutation of the NF 1 gene on chromosome 17 as the cause for inherited café‐au‐lait spots in this family. © 1993 Wiley‐Liss, Inc.
Newly recognized blepharofacioskeletal Syndrome
Authors: Richieri‐Costa A. , Guion‐Almeida M. L. , Rodini E. S. O. , Pereira S. C. S. , Cohen M. M.
Published: June 2005

A mother and daughter are described with similar facial and skeletal manifestations. The syndrome consists of blepharophimosis, malar hypoplasia, small thin lips, and long tapering fingers. The facial phenotype changes with age. Autosomal dominant inheritance is suggested. © 1993 Wiley‐Liss, Inc.
Unbalanced translocation, t(18;21), detected by fluorescence in situ hybridization (FISH) in a child with 18q– syndrome and a ring chromosome 21
Authors: McGinniss Matthew J. , Rosenberg Carla , Stetten Gail , Schinzel Albert A. , Binkert Franz , Petersen Michael B. , Kearns William G. , Kazazian Haig H. , Pearson Peter L. , Antonarakis Stylianos E.
Published: June 2005

We report on an 8‐year‐old girl with minor anomalies consistent with 18q‐syndrome and mild developmental delay. Initially cytogenetics showed a terminal deletion of chromosome 21 with mosaicism for a small ring chromosome 21 as the only apparent karyotypic abnormality: mos 45,XX,‐21/46,XX,+r(21) (48%/52%). Further studies including FISH and DNA analysis demonstrated a denovo unbalanced translocation of chromosomes 18 and 21 with the likely breakpoints in 18q23 and 21q21.1. Most of 21q was translocated to the distal long arm of one chromosome 18, and this derivative 18 appeared to lack 18q23‐qter. The small ring chromosome 21 [r(21)], present in only 52% of the patient's blood lymphocytes, did not appear to be associated with the abnormal phenotype since all 13 chromosome 21 markers that were examined in genomic DNA were present in 2 copies, and the phenotype of the patient was consistent with the 18q – syndrome. The Karyotype was reinterpreted as mos 45,XX,–18,–21,+der(18) t(18;21) (q23;q21.1)/46,XX, –18, –21,+der(18) t(18;21) (q23;q21.1), +r(21) (p13q21.1) (48%/52%). These results demonstrate the power of FISH in conjunction with DNA analysis for examination of chromosome rearrangements that may be misclassified by traditional cytogenetic studies alone. © 1993 Wiley‐Liss, Inc.
DNA analysis of cystic fibrosis in Brazil by direct PCR amplification from Guthrie cards
Authors: Raskin S. , Phillips J. A. , Krishnamani M. R. S. , Vnencak‐Jones C. , Parker R. A. , Rozov T. , Cardieri J. M. , Marostica P. , Abreu F. , Giugliani R. , Reis F. , Rosario N. A. , Ludwig N. , Pilotto R. F.
Published: June 2005

A 3 bp deletion of condon 508 (phenylalanine) of the cystic fibrosis (CF) gene constitutes the mutation of most CF chromosomes. The frequency of this mutation (referred to as ΔF508), varies considerably between populations, ranging form 26% of the CF mutations in Turkey to 88% in Denmark. To determine the frequency of the ΔF508 mutation in Brazilian Caucasoid CF patients, we used direct polymerase chain reacion (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards, followed by ethidium bromide staining of gels. Although the overall frequency of the ΔF508 mutation was 47% of 380 CF chromosomes from Brazilian Caucasoids born in five different states, significant inter‐state differences were observed, ranging from a ΔF508 frequency of 27% to 53%. While our method could be used to screen patients and their relatives for carrier testing and prenatal diagnosis, the efficacy of screening only for the ΔF508 mutation would be low, and would vary from state to state. Screening for a panel of local mutations will be needed to increase the mutation detection rate and optimize genetic counseling. © 1993 Wiley‐Liss, Inc.
Regional mapping of the gene for familial Mediterranean fever on human chromosome 16p13
Authors: Fischel‐Ghodsian Nathan , Bu Xiangdong , Prezant Toni R. , Oeztas Sitki , Huang Zhi‐Shen , Bohlman M. Charlotte , Rotter Jerome I. , Shohat Mordechai
Published: June 2005

Familial Mediterranean fever (FMF) is an autosomal recessively inherited inflammatory disorder characterized by recurrent short spisodes of fever, peritonitis, arthritis, and pleuritis. Recently, linkage was demonstrated between FMF and the VNTR probes 3′HVR and 5′HVR of the α‐globin complex at 16p13.3 ( = 0.06−0.10, Lodmax = 9.76−14.47) and the insertion/deletion polymorphism detected by the probe CMM65 of D16S84 ( = 0.04, Lodmax = 9.17). WE have now mapped the FMF gene between the two flanking markers D16S283/D16S291 ( = 0.038) and D16S80 ( = 0.159). The proximity of the microsatellite markers in D16S283 and D16S291 to the FMF gene allows preclinical diagnosis in most pedigrees with affected individuals. © 1993 Wiley‐Liss, Inc.
Supravalvular aortic stenosis cosegregates with a familial 6;7 translocation which disrupts the elastin gene
Authors: Morris Colleen A. , Loker James , Ensing Gregory , Stock A. Dean
Published: June 2005

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disorder characterized by abnormalities of development of the great vessels. SVAS is also commonly part of Williams syndrome. Linkage to the elastin gene on chromosome 7q11 has recently been reported in two kindreds with SVAS. Previous reports of patients with 7q11 deletions have noted great vessel abnormalities in some. We report on a family in which SVAS is cosegregating with a balanced reciprocal translocation, t(6:7) (p21.1;q11.23), providing further evidence that SVAS is the result of mutation of elestin at 7q11.23 region. The propositus of the translocation family has some minor anomalies which occur in Williams syndrome, Suggesting that elestin abnormalities may cause some of the abnormalities found in Williams syndrome. © 1993 Wiley‐Liss, Inc. © 1993 Wiley‐Liss, Inc.
Family with 22‐derived marker chromosome and late‐onset dementia of the Alzheimer type: II. Further cytogenetic analysis of the marker and characterization of the high‐level repeat sequences using fluorescence in situ hybridization
Authors: Percy Maire E. , Dearie Thomas G. , Jabs Ethylin Wang , Bauer Sharon J. , Chodakowski Barbara , Somerville Martin J. , Lennox Anne , McLachlan Donald R. C. , Baldini Antonio , Miller Dorothy A.
Published: June 2005

We have further characterized an unusual 22p+ marker chromosome with a double nucleolus organizer region (dNOR) previously identified in a family with late‐onset dementia of the Alzheimer type.

G‐banding and morphology of the marker's q arm were typically normal. However, the p+ arm had a terminal cytological satellite and a GT‐positive region at the midpoint. Standard C‐banding documented 2 C‐positive regions: one was associated with the primary centromere; the other, which was at the midpoint of the p arm, was not associated with a constriction. With replication‐banding, there was a darkly staining region in the middle of the p+arm that resembled the pericentromeric region of a chromosome 21 or 22. Fluorescence in situ hybridization with pXlr 101, a probe recognizing the full repeating unit of rDNA, indicated that the marker had an unusually large rDNA region; with pU 1.2, a probe recognizing the human rDNA promoter, the signal was a doublet. The marker had 2 signals with a β‐satellite probe, and a second signal in addition to that present at the primary centromere under low stringency with α‐satellite probes and a classic satellite probe. Immunostaining of chromosome spreads after R‐banding and ultraviolet (UV) denaturation showed that the major portion of the marker's p arm was highly methylated. © 1993 Wiley‐Liss, Inc.
Limb deficiency with or without Möbius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy
Authors: Gonzalez Claudette Hajaj , Vargas Fernando R. , Perez Ana Beatriz Alvarez , Kim Chong Ae , Brunoni Decio , Marques‐Dias Maria Joaquina , Leone Clea R. , Neto JordãO Correa , Llerena Juan C. , de Almeida José Carlos Cabral
Published: June 2005

Misoprostol, a synthetic analog of prostaglandin, has been widely used in Brazil as an abortifacient. Abortion is illegal in Brazil. An uncertain number of these abortion attempts are unsuccessful and the pregnancy continues. We report on 7 patients whose mothers attempted to abort using this drug in the first trimester of gestation without success. The 7 patients presented with limb defects and in 4 of them a diagnosis of Möbius sequence was made. © 1993 Wiley‐Liss, Inc.
Further delineation of Costello syndrome
Authors: Teebi Ahmad S. , Shaabani Issa S.
Published: June 2005

We report on a 6‐year‐old girl with Costello syndrome. Main manifestations included poor postnatal growth, relative macrocephaly, curly hair, distinct “coarse” face, mild mental retardation, happy and sociable personality, loose dark skin particularly of hands and feet, acanthosis nigricans, thin deep set nails, enamel hypoplasia of teeth, and hyperextensible joints. The absence to date of perioral and nasal papillomata in this girl suggests that Costello syndrome is clinically recognizable even before appearance of such papillomata. Manifestations are compared to the four previously reported sporadic cases. © 1993 Wiley‐Liss, Inc.
Costello syndrome: Further clinical delineation, natural history, genetic definition, and nosology
Authors: Zampino Giuseppe , Mastroiacovo Pierpaolo , Ricci Roberta , Zollino Marcella , Segni Giuseppe , Martini‐Neri Maria Enrica , Neri Giovanni
Published: June 2005

In 1977 Costello described two unrelated children with poor postnatal growth, mental retardation, curly hair, coarse face of similar appearance, and nasal papillomata, suggesting the existence of a previously undescribed syndrome of uncertain familial nature [Costello, Aust Paediatr J 13: 114–118, 1977]. The existence of this syndrome as a separate entity was substantiated several years later by two additional reports by Der Kaloustian et al. [Am J Med Genet 43:678–685, 1991] and Martin and Jones [Am J Med Genet 41:346–349, 1991]. More recently Borochowitz et al. [Am J Med Genet 43:678–685,1992] described a new “multiple congenital anomalies/mental retardation syndrome with facio‐cutaneous‐skeletal involvement.” Whether this condition should be considered separately from the Costello syndrome is currently a matter of debate. We present three cases, two of whom are sibs, who support the identity of the two syndromes.

Our aim is to better redefine the diagnostic criteria, describe the natural history, and confirm the genetic cause of the Costello syndrome, whose pattern of inheritance is most likely autosomal recessive. © 1993 Wiley‐Liss, Inc.
Combined pedigree and twin family study to determine the sources of variation in serum biotinidase activity: The usefulness of multiple study designs
Authors: Weissbecker Karen A. , Wolf Barry , Eaves Lindon J. , Marazita Mary L. , Nance Walter E.
Published: June 2005

Biotinidase, the enzyme responsible for recycling the vitamin biotin, is deficient in most individuals with late‐onset multiple carboxylase deficiency. Based on clinical criteria, biotinidase deficiency appears to be inherited as an autosomal recessive trait; however, the inheritance of biotinidase serum activity as a quantitative trait has not been studied previously. In this study, both segregation analysis of proband families and the analysis of twin family data were used to determine the relative contributions of a major gene, polygenes and environment to the variation in serum biotinidase activity. Segregation analysis of 24 families of biotinidase‐deficient individuals indicated that serum biotinidase activity is determined by the segregation of a single codominant major gene with the variability about the mean of each major genotype attributable to environmental effects. Significant polygenic effects could not be detected by this analysis. Variance component analysis of 128 twin families, which included the twins, their spouses, and their offspring, indicated that 70% of total variance in biotinidase activity is attributable to additive genetic effects, 22% to individual environmental effects, and 8% to shared environmental effects. The model also included an age effect for females. A portion (27%) of the estimated additive variance may be attributed to the segregation of the major gene. This study emphasizes the usefulness of studying multiple data sets representing different types of family relationships. © 1993 Wiley‐Liss, Inc.
Pallister‐Killian and Fryns syndromes: Nosology
Authors: McPherson Elizabeth W. , Ketterer Deborah M. , Salsburey Donna J.
Published: June 2005

Fryns syndrome is a lethal autosomal recessive multiple congenital anomaly syndrome characteristic “coarse” facies, cleft palate, diaphragmatic hernia, and distal digital hypoplasia. The appearance of the face and digits is very similar to that observed in Pallister‐Killian syndrome (mosaic isochromosome 12p), although the incidence of cleft palate, diaphragmatic hernia, and neonatal death is much lower in the latter condition.

We report on an infant with many manifestations of Fryns syndrome (“course” face, cleft palate, cloudy corneae, diaphragmatic hernia, distal digital hypoplasia, and neonatal death) who was found to be mosaic for i(12p). Her diagnosis was changed to Pallister‐Killian syndrome and the family was counselled accordingly.

The clinical overlap between Fryns and Pallister‐Killian syndromes is discussed. Because the chromosome abnormality in Pallister‐Killian syndrome is often limited to fibroblasts and may be selectively eliminated both in vivo and in vitro, some Pallister‐Killian patients may be misdiagnosed with Fryns syndrome and given an erroneously high recurrence risk. Newborn infants with the Fryns or Pallister‐Killian phenotypes should have chromosome studies involving multiple tissues so that the correct diagnosis can be made. This will contribute to the understanding of both disorders and facilitate appropriate genetic counselling. © 1993 Wiley‐Liss, Inc.
Joint contractures, hyperkeratosis, and severe hypoplasia of the posterior columns: A new recessive syndrome
Authors: Johnston Kathreen , Aarons Ralph , Schelley Susan , Horoupian Dikran
Published: June 2005

We report on 2 brothers with arthrogryposis, hyperkeratosis, and severe hypoplasia of dorsal roots and posterior columns in the one sib who was examined at autopsy. This appears to represent a new arthrogryposis syndrome with poor prognosis, most likely inherited as a single gene, either autosomal or X‐linked recessive trait. © 1993 Wiley‐Liss, Inc.
Whose DNA is it anyway? Relationships between families and researchers
Authors: Hannig Vickie L. , Clayton Ellen Wright , Edwards Kathryn M.
Published: June 2005

DNA obtained for research may, at a later time, become crucial for carrier and prenatal diagnosis. Continuing rapid advances in human genetics make this scenario more and more common. The following case illustrates some of the problems that may occur when DNA donors and researchers do not establish a verbal or written agreement at the time the DNA is obtained. The legal and ethical ramifications of this situation are examined through case discussion and review of the literature. We propose that even in the absence of a verbal or written agreement, researchers continue to have a responsibility to share any significant information obtained From linkage studies with donor families if such information becomes available. If the DNA specimens become critical for prenatal or carrier testing at a later time, we feel that the family has a right to request and receive aliquots of such specimens. The research unit should have the right to charge a storage fee for DNA banking. Clear agreement between donor and researcher at the time of specimen collection may avoid legal and ethical problems in the future. © 1993 Wiley‐Liss, Inc.
Smith‐fineman‐myers syndrome:Report on a large family
Authors: Wei Jianjun , Chen Bingxi , Jiang Yuan , Yang Yaping , Guo Yishou
Published: June 2005

Smith‐Fineman‐Myers syndrome is considered an x‐linked mental rertardation (XLMR) syndrome. Three families have been reported to date. However, none presented a typical pattern of X‐linked inhertance. Here we reported on 5 males with Smith‐Fineman‐Myers syndrome with similar phelnotypic expression as in those cases reported previously; they were distributed in 4 sibships of one large maternal kindred. This finding adds strong support to the hypothesis of the Smith‐Fineman‐Myers syndrome being a rare XLMR syndrome. © 1993 Wiley‐Liss, Inc.
Monosomy 11q: Report of two familial cases and review of the literature
Authors: Hustinx Roland , Verloes Alian , Grattagliano Bettina , Herens Christian , Jamar Mauricette , Soyeur Danial , Schaaps Jean‐Pierre , Koulischer Lucien
Published: June 2005

We present four children from two families with the typical 11q‐ phenotype resulting from an unbalanced segregation of a parental translocation. In the first family, the father had a 46,XY,t(5;11)(q24;q23.3) constitution. The father of the three other children had a 46,XY,t(11;17)(q23;p13) translocation. Despite associated partial deletion, three of the children has a typical 11q‐phenotype. The fourth one, whose pregnancy was terminated in the second trimester, had a hypoplastic left heart but no other considered gross anomalies. A review of 36 previous cases, including 5 due to translocation (4 familial rearrangements, and 1 of unknown origin) is given with emphasis on the relationships between breakpoints and phenotype. Undescribed manifestations in our patients include agenesis of corpus callosum adactyly and malrotation of the gut. © 1993 Wiley‐Liss, Inc.
Polysplenia syndrome and congenital short pancreas
Authors: Wainwright Helen , Nelson Matilda
Published: June 2005

We present a report of a stillborn female of mixed ancestry with congenitally short pancreas, polysplenia, congenital heart defect, normal bronchial branch pattern, and interruption of the inferior vena cava to add to the growing numbers (15) of this malformation complex in the literature. Additional mani‐festations were congenital hydrocephalus and absence of intestinal malrotation.

A recent poster presentation at the Second International Workshop on Fetal Genetic Pathology in Montana by Drut et al. underlined the importance of reporting these cases and of the pathological examination required [“Abnormal Slpleen Lobulation and Short Pancreas,” in Blastogenesis–Normal and Abnormal. New York: Wailey‐Liss, Inc. for the National Foundation–March of Dimes,1993]. © 1993 wiley‐Liss, inc.
Fetus in fetu:Molecular analysis of a fetiform mass
Authors: Hing Anne , Corteville Jane , Foglia Robert P. , Bliss David P. , Donis‐Keller Helen , Dowton S. Bruce
Published: June 2005

Fetus‐in‐fetu is a rare condition presenting as a calcified intra‐abdominal mass in the new‐born infant. Over 50 cases of fetus‐in‐fetu have been reported since 1800. Karyotype analysis in 8 cases and protein polymorphisms in 4 documented identical finding in the host and fetiform mass. We report a case of fetus‐in‐fetu in a newborn female including cytogenetic and molecular studies of both the host and mass. Genotypic information from 7 polymerase chain reaction (PCR) assays representing 4 chromosomes demonstrates heterozygous and identical alleles in the infant and fetus‐in‐fetu at all loci studied. A review of the literature is provided including a discussion regarding the impact of moleculer data on present hypotheses of fetus‐in‐fetu pathogenesis. © 1993 Wiley‐Liss, Inc.
Complex segregation analysis of antibodies to thyroid peroxidase in old order amish families
Authors: Pauls David L. , Zakarija Margita , McKenzie J. Maxwell , Egeland Janice A.
Published: June 2005

Autoimmune thyroid disease (AITD) may be characterized by the measurement in serum of antibodies to thyroid peroxidase. A population of Old Order Amish individuals and families was investigated to determine the prevalence of these antibodies and to examine hypotheses about the mode of transmission of thyroid antibodies. Complex segregation analysis were performed on 4 large multi‐generational Old Order Amish families composed of 26 nuclear families containing 199 first degree relatives. Several alternative hypotheses of genetic transmission were examined. Hypotheses of no transmission, polygenic inheritance, single locus transmission, and mixed inharitance were compared. The analyses incorporated population prevalences obtained from a random sample of of individuals. Result suggest that the pattern of transmission of thyroid antibodies in these families is consistent with a mixed model in which the major gene is transmitted in an autosomal dominant pattern. The mixed model postulates that there is a single gene of major effect as well as a polygenic component that can act separately and/or together to confer susceptibility for this phenotype. The parameter estimates for the major locus are: gene frequency (q), 0.16 ± 0.01; maximum male penetrance, 0.35; and maximum female penetrance, 0.70. The heritability of the polygenic background is estimated at 0.41. © 1993 Wiley‐Liss, Inc.
Prenatal diagnosis of hemophilia involving grandpaternal mosaicism
Authors: Lebo Roger V. , Koerper Marion A. , Kim Jong Hwa , Chueh Jane , Golbus Mitchell S.
Published: June 2005

Our Factor VIII and RFLP analyses identified previously unreported grandpaternal hemophilia A mosaicism in a male who transmitted the disease allele to 2 of 4 daughters and 2 of 4 grandsons. An uncommon flanking polymorphic DXS52 allele cosegregated with this grandpaternal mutant allele. This and other reports of mosaic hemophilia A carriers indicate that parental mosaicism can explain unusual segregation of loe Factor VIII activities and DNA polymorphism in about 1% of hemophilia A pedigrees. © 1993 Wiley‐Liss, Inc.
The Williams syndrome: Evidence for possible autosomal dominant inheritance
Authors: Sadler Laurie S. , Robinson Luther K. , Verdaasdonk Kathleen R. , Gingell Rebert
Published: June 2005

We recently evaluated a mother and son with the Williams syndrome. Documentation of the clinical phenotype in two generations of this family suggests that some cases of the Williams syndrome are autosomal dominantly inherited. Recognition of the heritable nature of the Williams syndrome should prompt careful clinical evaluation of other at‐risk relatives in order to provide accurate recurrence risk counseling. © 1993 Wiley‐Liss, Inc.
Metacarpophalangeal pattern profile analysis in Williams syndrome
Authors: Burns Michele A. , McLeod D. Ross , Linton L. R. , Butler Merlin G.
Published: June 2005

Many patients with Williams syndrome (WS) are not diagnosed until they are old enough to demonstrate the characteristic personality and facial changes. A number of these changes are quite subtle and none of them is present in all affected individuals. The cause of WS remains obscure and consequently, there are no cytogenetic, biochemical, or molecular studies to help in the diagnosis of patients in whom the diagnosis is uncertain. We have generated a mean WS metacarpophalangeal patten profile (MCPP) on 21 clinically diagnosed individuals with WS. This mean syndrome profile shows that WS hands are smaller than average age‐matched control hands and that the distal phalanx of the thumb is disproportionately large with respect to the rest of the hand. A mathematical model, which effectively discriminates WS patients from unaffected control individuals, was developed using discriminant analysis of the MCPP data. Of the 21 WS patients classified by this method, only 2 were misclassified as “normal.” Similarly, 2 of the 24 control individuals were misclassified as “WS”, yielding an overall successful classification rate of 91%. © 1993 Wiley‐Liss, Inc.
Williams syndrome: Autosomal dominant inheritance
Authors: Morris Colleen A. , Thomas Ioan T. , Greenberg Frank
Published: June 2005

Williams syndrome (WS) usually occurs sporadically. Few familial cases of Williams syndrome have been described, and those reports have often lacked photographic documentation. We describe 3 families, including a 3‐year‐old boy and his 34‐year‐old father, a 2‐year‐old girl and her 30‐year‐old mother, and a 3‐year‐old girl and her 31‐year‐old mother. None of these patients has supravalvular aortic stenosis or chromosome abnormalities. In all 3 families, the parent with Williams syndrome was diagnosed after the identification of the syndrome in the affected child. © 1993 Wiley‐Liss, Inc.
Blepharophimosis sequence (BPES) and microcephaly in a girl with del(3) (q22.2q23): A putative gene responsible for microcephaly close to the BPES gene?
Authors: Ishikiriyama Satoshi , Goto Michiyo
Published: June 2005

We report on a girl with the blepharophimosis sequence (BPES), microcephaly of postnatal onset, mild developmental retardation, and a deletion: 46,XX,del(3) (q22.2q23) de novo. A gene for BPES is suspected to be located at 3q23. Almost all cases with interstitial deletions containing 3q23 have not only BPES but also microcephaly and developmental retardation, while those without deletions, including those with apparently balanced translocations, only have BPES. Thus, a putative gene responsible for microcephaly may exist close to BPES gene. BPES, microcephaly, developmental retardation, and primary amenorrhea might constitute a contiguous gene syndrome. © 1993 Wiley‐Liss, Inc.
Mosaic r(13) in an infant with aprosencephaly
Authors: Goldsmith Claire L. , Tawagi George F. , Carpenter Blair F. , Speevak Marsha D. , Hunter Alasdair G. W.
Published: June 2005

We report on a stillborn male infant with a mosaic ring 13 karyotype (45,XY,−13/46,XY,−13,+r(13)) with apparennt aprosencephaly and clinical findings similar to those reported previously in the XK‐aprosencephaly syndrome. Findings of patients with r(13) are often similar to those seen in individuals with del(13q). This case was unusual because of the presence of aprosencephaly, although brain malformations such as arhinencephaly and cerebellar hypoplasia are present in at least one‐half of reported patients with 13q‐. The overlap between these syndromes suggests a possible chromosomal model of the XK‐aprosencephaly syndrome. © 1993 Wiley‐Liss, Inc.