bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple craniofacial anomalies associated with an interstitial deletion of chromosome 1(q21‐>q25)
Authors: Leichtman Lawrence G. , Strum Daniel , Brothman Arthur R.
Published: June 2005

We present a patient with an interstitial deletion of the chromosome 1q21‐>q25 that was diagnosed by amniocentesis. Significant malformations included: microbrachycephaly, bilateral cleft lip and palate, micrognathia, short neck, and athyroidia. The autopsy results demonstrate an overlap with several other postnatally ascertained patients and document the phenotype prenatally. © 1993 Wiley‐Liss, Inc.
Familial segregation of cervical ribs, sprengel anomaly, preaxial polydactyly, anal atresia, and urethral obstruction: A new syndrome?
Authors: Frydman Moshe , Cohen Herman A. , Ashkenazi Arie , Varsano Itzhak
Published: June 2005

In a consanguineous Jewish family originating from Bombay, India, the propositus presented with anal atresia, micropenis, urethral obstruction with secondary prune belly, omphalocele, patent urachus, and cryptorchidism. The kidneys were dysplastic and he had the Potter phenotype with limb deformities. Additional findings included IUGR with microcephaly, congenital heart defects, spinal anomalies, and hypoplastic lungs.

The mother and all three sisters had cervical ribs, and she and one sister had 11 pairs of thoracic ribs. The other two sisters had chronic immune thrombopenia. One of those had bilateral Sprengel deformity with homo‐vertebral bones, club feet, and microcephaly and the other sister also had unilateral preaxial hexadactyly.

Although familial segregation of cervical ribs and Sprengel deformity has been reported, the association of the findings in this family is unique and may represent a new syndrome. X‐linked dominant transmission may explain the severe manifestations in the affected male, but other modes of inheritance may also apply. © 1993 Wiley‐Liss, Inc.
Chromosome cultures from human cartilage
Authors: Urioste Miguel
Published: June 2005

Choosing the best post‐mortem biological tissue source for chromosomal studies is challenge for cytogeneticists. Acceptable cytogenetic results are difficult to obtain from macerated and necrosed tissues.

This report describes a method that is carried out after enzymatic digestion of cartilage from human fetuses and infants. It is currently employed successfully in our laboratory and our experience has shown that human cartilage could well be the tissue of choice for cytogenetic studies in stillborn fetuses and dead infants. © 1993 Wiley‐Liss, Inc.
Severe nonspecific X‐linked mental retardation caused by a proximally Xp located gene: Intragenic heterogeneity or a new form of X‐linked mental retardation?
Authors: Passos‐Bueno Maria Rita , Byth Barbara C. , Rosenberg Sergio , Takata Reinaldo I. , Bakker Egbert , Beggs Alan H. , Pavanello Rita C. , Vainzof Mariz , Davies Kay E. , Zatz Mayana
Published: June 2005

X‐linked mental retardation (XLMR) can be subdivided into syndromic and nonsyndromic or nonspecific. Patients with nonsyndroml XLMR show no characteristic manifestations, biochemical defects, or distinct fragile sites. Nevertheless, nonspecific XLMR seems to be heterogeneous. To determine the number and location of the genes responsible for XLMR, linkage studies in large pedigrees have to be performed. Here we report the data of linkage analysis in a large Brazilian family with 7 patients affected by a severe form of XLMR, with no other associated malformations. All the obligate carriers are normal. A close linkage without recombination (lod scores 1.95 and 3.25) was found between the disease locus and polymorphic DNA loci DXS255 (Xp11.22), DXS14 (Xp11.21). These results suggest tht the gene responsible for the disease in this family maps in the Xp11‐cent of the X chromosome. Positive lod score in this region have also been reported for other XLMR genealogie, but with a much milder phenotype. The possibility of intragenic or locus heterogeneity is discussed. © 1993 Wiley‐Liss, Inc.
Trisomy 4 in a fetus with cyclopia and other anomalies
Authors: Van Allen Margot I. , Ritchie Susan , Toi Ants , Fong Katherine , Winsor Elizabeth
Published: June 2005

We report on an 18‐week fetus with cyclopia, alobar holoprosencephaly, complex congenital heart defect, anal atresia, oligosyndactyly, cystic hygroma, and skeletal abnormalities with trisomy 4. Structural anomalies were detected on routine ultrasound of the pregnancy of a 17‐year‐old G3 P1 TAB1 woman with sickle cell trait. Trisomy 4 conceptuses usually miscary in the first trimester. We are aware of no other reports of a fetus with trisomy 4 and cyclopia. Causal association of chromosome abnormalities and holoprosencephaly sequence amay be more apparent in embryos and early fetuses than term fetuses because of poor viability of affected conceptuses. © 1993 Wiley‐Liss, Inc.
Detection of the cystic fibrosis delta‐F508 mutation at autopsy by site‐directed mutagenesis
Authors: Salcedo Mauricio , Chávez Margarita , Ridaura Cecilia , Moreno Manuel , Lezana José L. , Orozco Lorena
Published: June 2005

In Causasian populations cystic fibrosis (CF) is the most common autosomal recessive disorder. CF was previously considered rare in Mexico; however, the reported frequency is about 1% in autopsies. This discrepancy appears to be due to the inability to diagnose the illness during life. It is now known that in developing countries a great number of affected children die without the benefit of CF diagnosis and appropriate treatment. In this study we have used the PCR‐mediated sitedirected mutagenesis technique for the detection of the delta‐F508 mutation in a 6‐month old Mexican boy who died without definitive diagnosis. The tissue available from the child was a formaldehyde fixed paraffin‐embedded liver. We identified the delta‐F508 mutation in homozygous form in the propositus and in a heterozygous form in his parents. This represents the first report of CF molecular diagnosis in Mexico. © 1993 Wiley‐Liss, Inc.
Concordance and recessive inheritance of Leber congenital amaurosis
Authors: Lambert Scott R. , Sherman Stephanie , Taylor David , Kriss Anthony , Coffey Rebecca , Pembrey Marcus
Published: June 2005

Pedigrees were obtaines on 43 patients with confirmed Leber congenital amaurosis, a rare form of blindness caused by congenital dysfunction of the retina. All of the pedigrees were consistent with autosomal recessive inheritance and the segregation frequency using classical segregation analysis was 0.24 ± 0.07. Six of the 7 affected sib pairs were concordant in regards to systemic abnormalities. Despite previous reports that Leber congenital amaurosis can be inherited either as an autosomal dominant or recessive condition, our findings support only an autosomal recessive inheritance of this disorder. © 1993 Wiley‐Liss, Inc.
Rubinstein–Taybi syndrome with thymic hypoplasia
Authors: Kimura Hiroshi , Ito Yohko , Koda Yoshiro , Hase Yutaka
Published: June 2005

We report the autopsy findings in a 20‐month‐old boy with Rubinstein–Taybi syndrome and DiGeorge sequence. No Visible thymus was demonstrated at the time of autopsy. With careful microscopic examination, a few pieces of thymic tissues found near the thyroid gland showed remarkable depletion of both thymocytes and cortical epithelial cells. Immunohistological stanining with T‐cell. Surface antigens resulted in adefinite positive reaction. Repeated respiratory infections present in this patient may, in part, be attributable to thymic hypoplasia. Other major anomalies included broad thumbs and great toes, microphthalmia, arrhinencephaly, patent ductus arteriosus, stenosis of the uretero‐vesicular junction, bilateral cryptorchidism, and minor facial anomalies. © 1993 Wiley‐Liss, Inc.
Recombinant chromosome 9 possibly derived from breakage and reunion of sister chromatids within a paracentric inversion loop
Authors: Phelan Mary C. , Stevenson Roger E. , Anderson E. Vernon
Published: June 2005

Chromosomally unbalanced offspring resulting from the recombination of parental paracentric inversions are uncommon. We report on a 20‐month‐old boy with a partial duplication of 9p due to the recombination of a paternal paracentric inversion. The patient's recombinant chromosome was designated rec(9)(p13→p24::p12→p24::p12→qtr). The patient's father and paternal aunt have a paracentric inversion of chromosome 9:inv(9)(p13p24). Although several mechanisms have been proposed to explain the chromosome imbalance generated from paracentric inversions, none of the previously described mechanisms can account for the structure of the recombinant chromosome observed in the propositus. We propose an unusual mechanismas of formation involving breakage and unequal reunion of sister chromatids within the inversion loop to explain the structure of the patient's recombinant chromosome. © 1993 Wiley‐Liss, Inc.
Inguinal hernia and atrial septal defect in tel Hashomer camptodactyly syndrome: Report of a new case expanding the phenotypic spectrum of the disease
Authors: Franceschini P. , Vardeu M. P. , Signorile F. , Testa A. , Guala A. , Franceschini D. , Dalforno L.
Published: June 2005

We report on a girl with Tel Hashomer camptodactyly syndrome (THCS) born to first‐cousin parents. In addition to the usual findings, the patient had bilateral inguinal hernia and atrial septal defect, not previously described as component manifestations of the syndrome.

The present description expandns the phenotypic spectrum of the syndrome and gives new support to the hypothesized pleiotropic effects of the THCS gene on connective tissue. © 1993 Wiley‐Liss, Inc.
Fronto‐nasal dysostosis, callosal agenesis, crossed‐fused ectopia, tibial hemimelia, and preaxial polydactyly of feet: Severe expression of the acrocallosal syndrome?
Authors: Sueldo G. , Fernandes M. C.
Published: June 2005

We report on a girl with frontonasal “dysostosis,” callosal agenesis, crossed‐fused ectopia, tibial hemimelia, and preaxial polydactyly of feet. This pattern of the developmental defects suggests a severe form of the acrocallosal syndrome. Implications for genetic counselling are discussed. © 1993 Wiley‐Liss, Inc.
Mental retardation locus in Xp21 chromosome microdeletion
Authors: Fries Melissa H. , Lebo Roger V. , Schonberg Steven A. , Golabi Mahin , Seltzer William K. , Gitelman Stephen E. , Golbus Mitchell S.
Published: June 2005

Xp21 microdeletion syndrome is associated with variable size Xp21 deletions that usually include the glycerol kinase locus. The clinical phenotypes we studied in this chromosome region include: Xpter – Åland Island eye disease (AIED) ‐adrenal hypoplasia (AH) ‐glycerol kinase (GKD) ‐Duchenne muscular dystrophy (DMD) ‐retinitis pigmentosa (RP) ‐ornithine transcarbamylase (OTC) ‐centromere. In a compilation of 18 individuals in 14 families with the AH, GKD, and DMD loci deleted, 17 were male and all were developmentally delayed. In contrast, we report mentally retarded female carriers in two Xp21 deletion syndrome families with DMD, GKD, and AH in affected males. In the first family with normal karyotypes, a submicroscopic deletion was associated with DMD in the retarded male and with retardation in carrier females. In the second family an X chromosome with a cytogenetically deleted Xp21 distal to the OTC and RP genes segregated in the affected male and retarded female carriers. DNA analysis at the DMD locus verified the cytogenetic findings. This report of mental retardation in otherwise asymptomatic female carriers of Xp21 deletion classifies one form of mental retardation in females. © 1993 Wiley‐Liss, Inc.
Monitoring for new multiple congenital anomalies in the search for human teratogens
Authors: Khoury Muin J. , Botto Lorenzo , Waters Grady D. , Mastroiacovo Pierpaolo , Castilla Eduardo , Erickson J. David
Published: June 2005

The ability of birth defects monitoring to detect new human teratogenic and mutagenic agents may be limited if only isolated defects are monitored. Surveillance for “new” multiple congenital anormalies (MCA) may improve the detection of environmental agents associated with new defect patterns. To evaluate the feasibility of such monitoring, we examined data from two programs:1) the Metropolitan Atlanta Congenital Defects Program (MACDP), which ascertains infants with serious defects diagnosed in the first year of life, and, 2) the Italian Multicenter Register for Congenital Malformations (IPIMC), which ascertains newborn infants with birth defects from many hospitals in Italy. We focused on 24 relatively serious defects and defect groups. For a baseline period (MACDP: 1968–1988, 581,000 births; IPIMC: 1986–1989, 448,000 births), We identified all possible combinations of defects occurring in the same baby. For a test period (MACDP: 1989–1990, 77,000 births; IPIMC: 1990, 91,500 births), we identified babies with “new” MCA (i.e., combinations of defects not observed before in the system). During this period in MACDP, of the 85 babies with two or more defects, 9 babies had new MCAs. In IPIMC, of the 54 babies with two or more defects, 10 babies had new MCAs. A review of the records of infants with new MCAs in MACDP and IPIMC did not identify commonalities in maternal characteristics. This analysis illustrates the feasibility of monitoring for new MCAs in surveillance systems. This approach, complemented by an evaluation of exposures, may be a powerful additional tool in searching for human teratogens and mutagens. © 1993 Wiley‐Liss, Inc.
Congenital defects of the limbs in stillbirths: Data from a population‐based study
Authors: Froster Ursula G. , Baird Patricia A.
Published: June 2005

We analyzed limb deficiencies occurring in stillbirths with congenital anomalies registered in the Health Surveillance Registry of British Columbia between the years 1964 and 1984. Thirty stillborn infants presenting with various defects of the limbs were found during this time, giving an incidence of 39.52 in 10,000 stillbirth (1:253). This incidence is significantly higher than the incidence among liveborn individuals in the Province (5.97 in 10,000 livebirths or 1:1,842). Most cases involved the upper limbs, and most frequently the radius. Additional anomalies were present in 77% of cases, compared to 48% in liveborns. The study of stillbirth with congenital anomalies provides important information regarding the spectrum of birth defects seen in this group. This may be of relevance because of improved survival possibilities due to advances in perinatal care. © 1993 Wiley‐Liss., Inc. © 1993 Wiley‐Liss, Inc.
Terminal transverse limb defects and early chorionic villus sampling: Evaluation of 4,300 cases with completed follow‐up
Authors: Jahoda Milena G. J. , Brandenburg Helen , Cohen‐Overbeek Titia , Los Frans J. , Sachs Eva S. , Wladimiroff Juriy W.
Published: June 2005

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = (1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow‐up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC‐CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA‐CVS 98% of TC‐CVS was performed at 9–10 weeks, 80.7% of TA‐CVS procedures were carried out at 12–15 weeks. Selective termination took place in 97 cases of TC‐CVS (6.1%) and in 72 cases of TA‐CVS (2.6%). Another 8 Women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,645 TA) continuing pregnancies. The overall fetal loss rare <28 weeks was 5.4% (n = 80) for TC‐CVS and 2.6% (n = 70) for TA‐CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC‐CVS group (0.14%) against one (0.04%) in the TA‐CVS group. © 1993 Wiley‐Liss, Inc.
Mosaic isochromosome 8p
Authors: Tilstra David J. , Grove Marcia , Spencer Anne C. , Norwood Thomas H. , Pagon Roberta A.
Published: June 2005

Findings in a patient with mosaic isochromosome 8p are compared with those of previously reported cases. There were no distinguishing findings on physical examination; all had cognitive delays, especially in speech and language development. © 1993 Wiley‐Liss, Inc.
Reproductive risk in mating between two translocation carriers: Case report and review of the literature
Authors: Tsuji Kazushiro , Narahara Kouji , Yokoyama Yuji , Ninomiya Shinsuke , Yonesawa Suguru , Hiramatsu Yuji , Masaoka Hiroshi , Kudo Naofumi , Seino Yoshiki
Published: June 2005

We conducted a study to determine the reproductive risk in a couple who were translocation carriers. This couple, who carried balanced reciprocal translocations, experienced habitual abortions. The wife had a karyotype of 46,XX,t(7;13)(p15.3;q12.3) and the husband of 46,XY,t(1;7)(p11.1;p11.1). Chromosome study of their fourth abortus demonstrated a chimera consisting of two cell lines with a 46,XY and a 46,XX,t(1;7)(p11.1;p11.1)pat, −13, +der(7)t(7;13)(15.3;q12.3)mat, karyotype. A review of the literature indicates that the risk of having unbalanced live offspring or of spontaneous abortion/stillborns is similar in couples in whom both were translocation carriers and in couples in whom one individual was a translocation carrier. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gametes at fertilization or very early spontaneous abortions of unbalanced conceptuses. © 1993 Wiley‐Liss, Inc.
Origin of extraembryonic mesoderm in experimental animals: Relevance to chorionic mosaicism in humans
Authors: Bianchi Diana W. , Wilkins‐Haug Louise E. , Enders Allen C. , Hay Elizabeth D.
Published: June 2005

Confined chorionic mosaicism, a discordance in the karyotype between the fetus and placenta, occurs in 1% of chorionic villus sampling (CVS) cases. While the cytogenetic discrepancies occurring between different fetal tissues may pose clinical dilemmas, they can also be viewed as a natural experiment to determine early cell lineage relationship in the human. We reviewed extensive data in experimental animals to define the origin of the human extraembryonic mesoderm. The extraembryonic mesoderm in humans is important component of the CVS culture preparation. Previously, the extraembryonic mesoderm was thought to originate in the cytotrophoblast or primitive streak. More recent evidence supports its origin from the yolk sac, which does not always correlate with the fetal karyotype. We formulated a model of early human cell lineage and employed it to clarify clinical cases of chorionic mosaicism in two large published studies. © 1993 Wiley‐Liss, Inc.
Complete and partial XY sex reversal associated with terminal deletion of 10q: Report of 2 cases and literature review
Authors: Wilkie A. O. M. , Campbell F. M. , Daubeney P. , Grant D. B. , Daniels R. J. , Mullarkey M. , Affara N. A. , Fitchett M. , Huson S. M.
Published: June 2005

We describe 2 karyotypically male infants with terminal deletion of 10q and mental retardation, multiple phenotypic anomalies and abnormal genitalia. One [karyotype 46,XY,del(10)(q26.1)] had female external genitalia; the other [karyotype 46,XY,−10,+der(10)t(10;16)(q26.2;q21)] had an intersex phenotype. Of 8 males previously reported with terminal 10q deletion as the major or only cytogenetic abnormality, 2 had on intersex phenotype, and the others all had combinations of cryptorchidism, micropenis, and hypospadias. Terminal 10q deletions appear to be strongly associated with abnormal male genital development, and should be specificcally searched for in the cytogenetic workup of such cases. © 1993 Wiley‐Liss, Inc.
Robertsonian translocations: Clues to imprinting
Authors: Donnai Dian
Published: June 2005

Robertsonian translocations, occurring with a frequency of about 1 in 10,000 livebirths, may be an important cause of uniparental disomy as demonstrated for 13/15, 13/14, 14/14, and 22/22 translocations. Dysmorphogenesis and/or mental retardation provide clinical clues for uniparental disomy in apparently balanced offspring of translocation carriers. Research strategies for assessing frequency and implications of uniparental disomy in translocation carriers include a genetic register approach, study of abortuses from balanced translocation carriers, and parent‐of‐origin studies on de novo homologous Robertsonian translocations. © 1993 Wiley‐Liss, Inc.
Frontonasal dysplasia in two successive generations
Authors: Fryburg Julie S. , Persing John A. , Lin Kant Y.
Published: June 2005

Frontonasal dysplasia is thought to be a sporadic condition limited to the face and head. We describe a family from the Bahamas in which a mother, 2 of her children, and the mother's brother have variable manifestations of frontonassal dysplasia. The mother has extremely mild expression, but her brother and 2 sons are more severly affected. Besides polydactyly no other birth defects were noted in any other relatives. The pedigree is consistent with autosomal or X‐linked dominant inheritance. A description of each patient is presented along with a discussion of the genetic counseling issue and review of the literature for other possibly familial cases of frontonasal dysplasia. © 1993 Wiley‐Liss, Inc.
Moving satellites and unstable chromosome translocations: Clinical and cytogenetic implications
Authors: Farrell S. A. , Winsor E. J. T. , Markovic V. D.
Published: June 2005

We describe 2 families in which acrocentric short arm material moved from one chromosome to another. In case 1, a meiotic event resulted in movement of an unusually large paternal 21p to chromosome 13 in the fetus. In case 2, a mitotic event resulted in fetal mosaicism. The short arm material from a paternal chromosome 15 moved to chromosome 14 in some of the fetal cells. Movement of acrocentric short arm material resulted from breakage and exchange in centromeric areas of repetitive DNA. We suggest the mechanism may be similar to that of previously reported “jumping” translocations.

Failure to recognize movement of the short arms of acrocentric chromosomes can result in erroneous interpretation of prenatal cytogenetic results and of other cytogenetic assays dependent on acrocentric short arm polymorphisms. © 1993 Wiley‐Liss, Inc.
Congenital nonprogressive myopathy with Möbius and Robin sequence—the Carey‐Fineman‐Ziter syndrome: A confirmatory report
Authors: Schimke R. Neil , Collins Debra L. , Hiebert John M.
Published: June 2005

Recently, we evaluated a 27‐month‐old boy with congenital generalized nonspecific myopathy, Möbius sequence, Robin sequence, and failure to thrive. We think the child has the same entity described by Carey, Fineman, and Ziter in 1982 [J Pediatr 101:353–364] and as such represents only the third example of this unusual syndrome. Review of the large number of conditions in which the Robin sequence occurs supports heterogeneity.

Our case strengthens the Möbius‐Robin association and further defines the Carey‐Fine‐man‐Ziter syndrome as a viable entity. It is most likely inherited as an autosomal recessive trait. © 1993 Wiley‐Liss, Inc.
Hypertrichosis, atrophic skin, ectropion, and macrostomia (Barber‐Say syndrome): Report of a new case
Authors: Santana S. Martínez , Alvarez F. Pérez , Frías J. L. , Martínez‐Frías M.‐L.
Published: June 2005

We report on a child, born to a consanguineous parents, who presented with a multiple congenital anomalies (MCA) pattern consisting of severe hypertrichosis, macrostomia, ectropion, and atrophic skin. To our knowledge this is the third case with this combination of defects. The two previous cases were reported by Barber et al. [Syndrome Identification VIII(1):6–9, 1982], and David et al. [Am J Med Genet 41:192–195, 1991]. © 1993 Wiley‐Liss, Inc.
Further delineation of the epidermal nevus syndrome: Two cases with new findings and literature review
Authors: Grebe Theresa A. , Rimsza Mary E. , Richter Sarah F. , Hansen Ronald C. , Hoyme H. Eugene
Published: June 2005

“Epidermal nevus syndrome” (“ENS”) is a neurocutaneous disorder in which epidermal nevi are associated with other abnormalities, most commonly of the skeletal and central nervous systems. We present two cases of epidermal nevus syndrome (ENS) with very different clinical findings. The first case is a newborn with multiple linear epidermal nevi of the trunk and limbs, and several other anomalies, including bony duplications of the lower limbs and hypoplastic left heart syndrome. The second patient, a 6‐year‐old boy, has a linear nevus sebaceous of the scalp with severe CNS involvement, including generalized seizures, moderate mental retardation, microcephaly, and a left hemiparesis. He also has genitourinary, cardiac, and skeletal defects. These two patients exhibit several abnormalities not previously recognized and illustrate the wide clinical spectrum of “epidermal nevus syndrome.” We present a review of the clinical findings in 74 cases of “ENS.” Correlation was noted between the presence of skin lesions located on the head and CNS involvement. The wide clinical spectrum of “ENS” as illustrated by these two patients suggests that “ENS” is a causally heterogeneous group of disorders. © 1993 Wiley‐Liss, Inc.
Cerebro‐reno‐digital (Meckel‐like) syndrome with Dandy‐Walker malformation, cystic kidneys, hepatic fibrosis, and polydactyly
Authors: Genuardi Maurizio , Dionisi‐Vici Carlo , Sabetta Gaetano , Mignozzi Massimo , Rizzoni Gianfranco , Cotugno Giovanna , Neri Maria Enrica Martini
Published: June 2005

We report on a boy with several findings of the Meckel syndrome, such as hepatic fibrosis, polycystic kidneys, post‐axial hexadactyly, and genital abnormalities, but a Dandy‐Walker malformation rather an occipital meningocele. Progressive deterioration of renal function beginning at 37 months led to death at 43 months. Both Dandy‐Walker malformation and survival to the fourth year are unusual findings in Meckel syndrome. This uncommom combination represents a further demonstration of the pleiotropy/heterogeneity of the cerebro‐reno‐digital syndromes. © 1993 Wiley‐Liss, Inc.
Interrelationships of the hemifacial microsomia‐VATER, VATER, and sirenomelia phenotypes
Authors: Duncan Peter A. , Shapiro Lawrence R.
Published: June 2005

The phenotypes of hemifacial microsomia‐VATER, VATER, and sirenomelia patients suggest a sequence of overlapping developmental abnormalities. The malformations of 247 hemifacial microsomia (HFM) patients with one or more anomalies in other body regions were analyzed and compared with those of 255 VATER and 101 sirenomelia patients studied in the same fashion. The HFM patients were analyzed in four subgroups delineated by the number of their concomitant VATER ascertainment abnormalities (VAA). Three or more VAA occurred in 33 HFM patients who were designated to have the HFM‐VATER phenotype and while no significant alteration of the HFM phenotype was found, there were notable differences in the analyses of the 20 malformation categories studied.

Analyzed in separate heart and blood vessel (BV) categories, occurrences of BV defects in HFM patients with 0–1 VAA were low (4–6%) and due to anomalies other than sigle umbilical arteries (SUA). The BV abnormalities increased to 20% in the HFM with two VAA, HFM‐VATER, and VATER phenotypes with equal occurrence of SUA and other BV anomalies. The incidence of SUA was markedly increased (64%) in the sirenomelia. Heart defects rose from 22% to 40% with the increasing VAA in individual HFM patients but were less in VATER (29%) and sirenomelia (21%) patients and were attributed to complex conotruncal, and other early embryonic anomalies. Unilateral agenesis of paired organs systems occurred frequently and, possibly, can be attributed to an absent blood supply.

Each phenotype of the sequence also had increased VAA, rib/vertebrae hypersegmentation, and monozygotic twinning. The variation in the incidences of malformations in the three phenotypes can be attributed to their relative location in the craniocranial organogenesis sequence of normal human embryologic development. © 1993 Wiley‐Liss, Inc.
Hereditary nodular heterotopia accompanied by mega cisterna magna
Authors: Oda Takaya , Nagai Yukiyo , Fujimoto Shinji , Sobajima Hisanori , Kobayashi Masanori , Togari Hajime , Wada Yoshiro
Published: June 2005

This is the first report of hereditary nodular heterotopia accompanied by mega cisterna magna. Magnetic resonance imaging documented multiple bilateral subependymal nodules, which were isointense to gray matter. This disease entity is considered a dominant trait, since the mother and two daughters, half‐sisters, were affected. © 1993 Wiley‐Liss, Inc.
Hydrops‐ectopic calcification—moth‐eaten skeletal dysplasia (Greenberg dysplasia): Prenatal diagnosis and further delineation of a rare genetic disorder
Authors: Chitayat David , Gruber Helen , Mullen Brendan J. , Pauzner David , Costa Teresa , Lachman Ralph , Rimoin David L.
Published: June 2005

An offspring of consanguineous parents of East‐Indian origin was found prenatally to have hydrops fetalis, short limb dwarfism, polydactyly and chondro‐osseous changes consistent with Greenberg hydrops‐ectopic calcification–moth‐eaten skeletal dysplasia (HEM) dysplasia. The radiological changes include platyspondyly with multiple extra ossification centers, extraneous calcification in the ribs, sternum, pelvis, and epiphysis, and moth‐eaten long bones. The histopathological changes included chondrocytes with dilated rough endoplasmic reticulum and inclusion bodies with homogeneous material of intermediate electron density.

These findings further delineate the spectrum of this rare autosomal recessive skeletal dysplasia. © 1993 Wiley‐Liss, Inc.
Möbius sequence: Further in vivo support for the subclavian artery supply disruption sequence
Authors: Charles Steven St. , Dimario Francis J. , Grunnet Margaret L.
Published: June 2005

Möbius sequence consists of a congenital bilateral facial nerve palsy and external ophthalmoplegia often associated with malformations of the limbs and orofacial structures. The pathogenesis of the sequence is a subject of debate. However, a new hypothesis proposes that Möbius sequence results from an interruption of embryonic blood supply (subclavian artery supply disruption sequence). Here we present an infant with bilateral facial nerve palsy (VII), external ophthalmoplegia (IV, VI), paresis of cranial nerves V, IX, X, XI, and XII, absence of the pectoralis major muscle (Poland anomaly), terminal transverse limb defects, and absence of the right diaphragm. Also, he was found to have discrete foci of brainstem calcifications in the region of the dorsal respiratory group on both CT scan and the histologic sections with microscopic evidence of diffuse brainstem “injury.” The anomalies and histopathology noted in this infant imply that vascular insufficiency prior to the sixth week of gestation involving the proximal sixth intersegmental artery may result in the manifestations presented in this report and lend further support for the existence of a subclavian artery supply disruption sequence. © 1993 Wiley‐Liss, Inc.
Variable clinical expression of mosaic trisomy 16 in the newborn infant
Authors: Devi Anne S. , Velinov Milen , Kamath M. Vasudeva , Eisenfeld Leonard , Neu Richard , Ciarleglio Leslie , Greenstein Robert , Benn Peter
Published: June 2005

Trisomy 16 is common in embryos and fetuses aborted early during development. Mosaicism for trisomy 16 is sometimes encountered during prenatal diagnosis, particularly with chorionic villi biopsy specimens, and, until recently, was thought to be confined to the placenta. However, recently, several liveborn infants with trisomy 16 mosaicism have been described. We report on an additional liveborn infant with trisomy 16 mosaicism and compare the clinical findings with those of the previously reported cases in an attempt to delineate a mosaic trisomy 16 syndrome. Cytogenetic analysis from our patient showed that there was a different proportion of abnormal cells in different tissues and that the anomaly was undetectable in blood lymphocyte cultures. This observation was consistent with some of the previous reports. DNA analysis of parents and child was carried out using a polymorphic dinucleotide marker that maps to the long arm of chromosome 16. This analysis showed that the extra chromosome 16 in the infant was maternal in origin and suggested that the nondisjunction was probably a first meiotic division error. Our results suggest that an investigation of multiple tissues is required before concluding that mosaicism is confined to the placenta. We conclude that a finding of trisomy 16 mosaicism at prenatal diagnosis should be regarded with extreme caution. This diagnosis may be associated with a highly variable phenotype that may occasionally be compatible with extrauterine life. © 1993 Wiley‐Liss, Inc.
Cleft palate‐lateral synechiae syndrome: Report on three new patients with additional findings and evidence for variability and heterogeneity
Authors: Nakata Nancy M. K. , Guion‐Almeida M. L. , Costa Richieri
Published: June 2005

We report on 3 Brazilian children with short stature, microcephaly, cleft palate, lateral synechiae, and mild mental retardation. One patient was an isolated case and the other had an equally affected brother. Genetic aspects and phenotypic manifestations are compared with those of previous reports with oral synechiae. Recurrence in sibs suggests autosomal recessive inheritance. © 1993 Wiley‐Liss, Inc.
Two sibs with different phenotypes due to adjacent‐1 segregation of a subtle translocation t(4;5)(p16.3;p15.3) mat
Authors: Qumsiyeh Mazin B. , Stevens Cathy A.
Published: June 2005

High‐resolution chromosome banding and in situ hybridization with combined cosmid and alphoid sequence probes were used to delineate a very small reciprocal translocation in a mother and her two children. The first child has a 46,XX,der(4)t(4;5)(p16.3;p15.3)mat and thus has a deletion of 4p16.3→pter and a duplication of 5p15.3→pter (most likely 5p15.31→pter). Clinical findings include marked growth retardation, developmental delay, seizure disorder, microcephaly, unruly hair, broad nasal tip, downturned mouth, narrow palate, 11 pairs of ribs,mild right club foot, and a deep sacral dimple. Thus, this child has only a few non‐specific manifestations of Wolf‐Hirschhorn syndrome. The second child has a 46,XY,der(5)t(4;5)(p16.3;p15.3)mat; thus a deletion of 5p15.3→pter and a duplication of 4p16.3→pter. He has failure to thrive, developmenatal delay, microcephaly, sparse hair, horizontal nystagmus, short upturned nose with flared nostrils, thin lips with overhanging upper lip, long fingers and toes, and hypertonicity. Findings in the second patient are not suggestive of cri du chat syndrome (del 5p). The mother is phenotypically normal. This translocation will be useful in mapping genes and markers on the 4p and 5p chromosomal regions. © 1993 Wiley‐Liss, Inc.
Mucolipidosis type IV: A mild form with late onset
Authors: Ries Shmuel , Sheffer Ruth N. , Merin Saul , Luder Anthony S. , Bach Gideon
Published: June 2005

A 16‐year‐old girl is presented with mild clinical manifestations and late onset of mucolipidosis type IV (MLIV). The patient, an Ashkenazi Jew, has had minor motor difficulties and mild psychological disturbances since early childhood. Her vision began deteriorating at 12 years of age, due to bilateral corneal opacities and retinal degeneration. At present she attends a regular high school, although she is slow and scholastic achievements are lower than average. Electron microscopic examination and biochemical studies were typical for MLIV, namely, abnormal ganglioside retention and typical pattern of phospholipids accumulation. This very mild presentation of MLIV suggests a broader spectrum of heterogeneity of this disorder and raises the possibility that MLIV, at least among Ashkenazi Jews, might be more frequent than estimated hitherto, due to undiagnosed mild patients. © 1993 Wiley‐Liss, Inc.
“Holoprosencephaly‐polydactyly” (pseudotrisomy 13) syndrome: Expansion of the phenotypic spectrum
Authors: Lurie Iosif W. , Wulfsberg Eric A.
Published: June 2005

Analysis of familial cases of the so called “holoprosencephaly‐polydactyly” (“pseudotrisomy 13”) syndrome shows that neither holoprosencephaly, nor polydactyly are obligatory manifestations of this condition. This review of previous case report shows that each of these anomalies is only found in approximately 60% of affected sibs, and therefore these sentinel abnormalities are not required for diagnosis. We propose a widening of the phenotypic spectrum of this syndrome and consideration of the use of an eponomic name, such as the Cohen‐Gorlin syndrome, or clear recognition that the sentinel findings of holoprosencephaly and polydactyly are not essential for diagnosis. We propose the following diagnostic criteria for the syndrome. The diagnostic criteria for sporadic cases would include a normal karyotype and either (1) a combination of holoprosencephaly and postaxial polydactyly with or without other characteristics, or (2) a combination of holoprosencephaly with other characteristics but without polydactyly, or (3) a combination of postaxial polydactyly, brain defects (microcephaly, hydrocephaly, agenesis of corpus callosum) and other characteristics. The diagnostic criteria for the familial cases would be the same, except that, as long as the other sibs have no abnormalities contradicting the diagnosis, a normal karyotype would be required in only one affected sib. © 1993 Wiley‐Liss, Inc.
Lower lip pits and complete idiopathic precocious puberty in a patient with Kabuki make‐up (Niikawa‐Kuroki) syndrome
Authors: Franceschini P. , Vardeu M. P. , Guala A. , Franceschini D. , Testa A. , Corrias A. , Chiabotto P.
Published: June 2005

We report on a 13½‐year‐old patient with Kabuki make‐up syndrome and complete idiopathic precocious puberty manifested at 7½ years. In addition to the other specific clinical signs, she showed hypodontia and lower lip pits, as typically seen in the Van der Woude syndrome. The significance of lower lip pits in the Kabuki make‐up syndrome in discussed. © 1993 Wiley‐Liss, Inc.
Váradi syndrome (OFD VI) or opitz trigonocephaly syndrome: Overlapping manifestations in two cousins
Authors: Cleper Roxana , Kaushchansky Arieh , Varsano Itzbak , Frydman Moshe
Published: June 2005

We report on 2 cousins, offspring of consanguineous matings, with multiple congenital anomalies. Square face, frontal bossing with metopic ridge, small antverted nose, flat nasal bridge, slantd palpebral fissures, and epicanthal folds contributed to an unusual appearance. Multiple bucco‐alveolar frenula and notched inferior alveolar ridges were present at birth and one had a notched uvula and submucous cleft of the hard palate. Both had congenital heart anomalies, micropenis, and cryptorchidism. Persistence of Müllerian structures was documented at necropsy in one patient. The surviving patient was mentally retarded and had unilateral central hexadactyly and partial agenesis of the corpus callosum. Bulimia and episodic hyperthermia were attributed to hypothalamic dysfunction. Results of unstimulated endocrine studies and gonadotropin releasing hormone (GnRH), and human chorionic gonadotropin (HCG) stimulation tests were normal. The manifestations of the 2 patients overlap those reported in the OFD VI and Opitz trigonocephaly syndromes. © 1993 Wiley‐Liss, Inc.
Williams–Beuren syndrome in monozygotic twins with variable expresion
Authors: Pankau Rainer , Gosch Angela , Simeoni Eva , Wessel Armin
Published: June 2005

Five sets of monozygotic (MZ) twins with Williams–Beuren syndrome (WBS) have been reported so far. We report on an additional pair of mz twins concordant for WBS but variable expression for the syndrome. Although both faces look different monozygosity of the twins was proven by DNA fingerprint analysis. HLA, and blood group pattern. Both girls had the typical facial appearance with strabismus. Both had developmental delay, mild supravalvular aortic stenosis (SVAS), hypoplasia of both pulmonary arteries and multiple peripheral pulmonary stenoses, and inguinal hernia. Unilateral renal agenesis was seen in one of the twins. In addition the pedigree pointed to a second disorder with probably autosomal dominant inheritance. Both twins had a cleft palate, but their father had cleft lip and the grandfather as well as the greatgrandfather had cleft lip/palate. Findings of linkage analysis in pedigrees with nonsyndromic oral facial cleft were taken to suggest that a major locus for nonsyndromal oral facial cleft is located on the distal portion of chromosome 6. Linkage studies could serve as a starting point to examine a locus associated with WBS. Our observation and reports on the literature support the hypothesis that WBS is a genetic disorder. © 1993 Wiley‐Liss, Inc.
Inverted duplication of 8p: Ten new patients and review of the literature
Authors: Feldman Gerald L. , Weiss Lester , Phelan Mary C. , Schroer Richard J. , VanDyke Daniel L.
Published: June 2005

We evaluated 10 patients with an inverted tandem duplication of 8p. Inverted duplications of chromosome 8 have been reported infrequently, and no syndrome has been previously identified. All 8 patients on whom birth histories were available were hypotonic at birth, and had feeding difficulties in the neonatal period. All patients have significant developmental delay. Manifestaions present in 5 or more patients were prominent forehead, high arched palate, large mouth with a thin upper lip, malformed and/or apparently lowset ears, broad nasal bridge, dental and skeletal abnormalities, and joint laxity or hyperextensibility. Variation in the phenotype may, in part, be explained by the different breakpoints. Recurrence risks of de novo rearrangements are probably very low, but for the recombinants the risk may be significant.

The duplication appeared to be de novo in 6 patients (both parental karyotypes were normal); maternal karyotypes were normal in 2 patients, and both parrents of 1 patient were not available. One propositus had a monocentric recombinant of a paracentric inv(8) (p12p23.3) carried by the mother, and is one of only 6 known cases of duplication associated with a balanced paracentric inversion in a parent. The carrier parent was the mother in 5 of those 6 cases. Each case involved a different chromosome, and each probably was created by an unusual meiotic recombination event.

Inverted duplication 8p is one of the most common duplications observed in our laboratories, and ranks in frequency with the classical deletions, such as Wolf‐Hirschhorn and cri‐du‐chat syndromes and duplication or secondary trisomy 15ql. Since 1/7 cases with complete parental karyotypes was associated with a familial rearrangement, parental karyotype studies should be considered in all cases of tandem duplication. © 1993 Wiley‐Liss, Inc.
Persistence of müllerian derivatives, lymphangiectasis, hepatic failure, postaxial polydactyly, renal and craniofacial anomalies
Authors: Urioste Miguel , Rodríguez José I. , Barcia José M. , Martín Martín , Escribá Rosa , Pardo Marina , Camino J. , Frías MaríA Luisá Martínez‐
Published: June 2005

We describe 3 unrelated newborn males with a previously unreported constellation of conenital anomalies. All 3 died neonatally of hepatic failure. Clinically, they presented with a pattern of malformations characterized by prenatal linear growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, and postaxial polydactyly. All 3 cases had male extenal genitalia with cryptorchidism, and 2 of them, a small penis. Necropsies showed similar internal anomalies, consisting müllerian duct remnants, lymphangiectasis, and renal anomalies. The karyotypes were normal (46, XY) in skin fibroblasts (Case 1) and in peripheral blood lymphocytes (Case 3).

Although this pattern of congenital anomalies must be differentiated from several other lethal syndromes, to our knowledge, no similar cases have been described previously.

Cause of this syndrome is unknown. Because Case 2 had a previous brother with similar anomalies, we suspect that this new entity probably is an autosomal recessive or X‐linked trait. © 1993 Wiley‐Liss, Inc.
Nonimmune hydrops fetalis in a 49,XXXXY fetus at 16 menstrual weeks
Authors: Hovav Y. , Nadjari M. , Dagan J. , Kafka E. , Yaffe H.
Published: June 2005

Amniocentesis of a fetus with a sonography diagnosis of nonimmune hydrops fetalis and bilateral clubfoot deformity at 16 weeks of gestation showed a chromosome constitution 49,XXXXY. © 1993 Wiley‐Liss, Inc.
Non‐allelic heterogeneity of familial adenomatous polyposis
Authors: Tops Carli M. J. , Van Der Klift Heleen M. , Van Der Luijt Rob B. , Griffioen Gerrit , Taal Babs G. , Vasen Hans F. A. , Khan P. Meera
Published: June 2005

Linkage studies on familial adenomatous polyposis (FAP) reported so far suggest that FAP is a genetically homogeneous disease. Recently, we found that the putative gene for Turcot syndrome, an apparently autosomal recessive clinical variant of FAP, is not allelic to FAP. Here we describe another family, segregating for an autosomal dominant disease clinically indistinguishable from FAP but genetically not linked to the APC locus, adding further evidence for the occurrence of non‐allelic heterogeneity of FA. These observations have implications to the linkage‐based genetic counselling of persons at risk for FAP especially when they are drawn from small families giving insufficient information. © 1993 Wiley‐Liss, Inc.
Saethre‐Chotzen syndrome with familial translocation at chromosome 7p22
Authors: Reid Cheryl S. , McMorrow Lydia E. , McDonald‐McGinn Donna M. , Grace Kimberly J. , Ramos Feliciano J. , Zackai Elaine H. , Cohen M. Michael , Jabs Ethylin Wang
Published: June 2005

Chromosome analysis of a male infant and his mother with Saethre‐Chotzen syndrome demonstrated an apparently balanced translocation, t(2;7)(p23;p22). This association lends support to localization of the gene for Saethre‐Chotzen syndrome to the 7p2 region and supports further involvement of gene(s) in the 7p22 region. © 1993 Wiley‐Liss, Inc.
Compromise of the spinal canal in Proteus syndrome
Authors: Skovby Flemming , Graham John M. , Sonne‐Holm Stig , Cohen M. Michael
Published: June 2005

We report on 2 children with spinal stenosis and neurologic sequelae. They illustrate the 2 ways in which spinal compromise may develop in Proteus syndrome—vertebral anomalies or tumor infiltration. In one patient, spinal stenosis resulted from an angular kyphoscoliosis. In the other, cord compression resulted from infiltration of a paraspinal, intra‐thoracic angiolipoma. © 1993 Wiley‐Liss, Inc.
Acrofacial dysostoses: Review and report of a previously undescribed condition: The autosomal or X‐linked dominant catania form of acrofacial dysostosis
Authors: Opitz John M. , Mollica Florindo , Sorge Giovanni , Milana Gabriella , Cimino Gabriella , Caltabiano Mario
Published: June 2005

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders combining defects of craniofacial and limb development. The predominantly preaxial form is called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known as the Genée‐Wiedemann or Miller syndrome. The former appears to be about twice as common as the latter with well‐documented autosomal dominant and recessive occurrences in both conditions. Only 1 AD occurrence of POADS is known, but 5 sets of sibs are suggestive of AR inheritance. Heterogeneity of apparently nonsyndromal AFD of both types is powerful support for the hypothesis that the AFDs are polytopic field defects arising during blastogenesis. Six other previously described forms of AFD include the AFD syndrome of Kelly et al. (AR), the Rodríguez or Madrid form of AFD (AR or XLR), the Reynolds or Idaho form of AFD (AD), the Arens or Tel Aviv type of AFD (AF?), the presumed AR AFD syndrome of Richieri‐Costa et al., and the AD Patterson–Stevenson–Fontaine syndrome. Here we review the AFDs and report on a previously apparently undescribed autosomal or X‐linked dominant form of AFD with mental retardation in a Sicilian mother and her 4 sons. © 1993 Wiley‐Liss, Inc.