bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Erasure of the Imprint on a Fragile X Chromosome When Transmitted by a Male
Authors: Laird Charles D.
Published: June 2005

Although most males with the fragile‐X [fra(X)] syndrome do not reproduce, there are 2 published pedigrees that include affected males who have daughters and who thus appear to have transmitted the fragile‐X chromosome to their progeny. In addition, one published fra(X) pedigree includes an apparently normal male who expresses cytogenetically the fra(X) site at high frequency and who has 3 daughters. In the 6 daughters of these 3 males, there is little or no cytogenetic expression of the fra(X). I interpret these pedigrees within the context of my X‐inactivation imprinting model of the fra(X) syndrome (Genetics 117:587–599): the cytogenetic manifestation of the imprinted state of the mutant fra(X) chromosome [high percentage of cytogenetic expression] is no longer present in daughters of imprinted males. I propose that the imprinted state is erased when an imprinted fragile‐X chromosome is passed through a male. Such erasure in the gender opposite to the gender that established the imprint is in accord with other examples of chromosome imprinting in mammals. Additional data from unpublished fra(X) pedigrees are requested.
Guidelines for the Preparation and Analysis of the Fragile X Chromosome in Lymphocytes
Authors: Jacky P. B. , Ahuja Y. R. , Anyane‐Yeboa K. , Breg W. R. , Carpenter N. J. , Froster‐Iskenius U. G. , Fryns J.‐P. , Glover T. W. , Gustavson K.‐H. , Hoegerman S. F. , Holmgren G. , Howard‐Peebles P. N. , Jenkins E. C. , Krawczun M. S. , Neri G. , Pettigrew A. , Schaap T. , Schonberg S. A. , Shapiro L. R. , Spinner N. , Steinbach P. , Vianna‐Morgante A. M. , Watson M. S. , Wilmot P. L.
Published: June 2005

The following guidelines were adopted by an Ad Hoc Committee convened at the Fourth International Workshop on the Fragile X Syndrome and X‐Linked Mental Retardation to establish minimum cytogenetic standards for the preparation and analysis of the fragile X chromosome. The intention of the committee was to develop and provide practical standards for the routine cytogenetic detection of the fragile X. The guidelines describe reasonable criteria for effective tissue culture methods for eliciting the Xq27.3 fragile site in vitro and for the analysis of such chromosome preparations.
Mental impairment in cytogenetically positive fragile X females
Authors: Cronister Amy , Hagerman Randi J. , Wittenberger Michael , Amiri Khaled
Published: June 2005

Prenatal diagnosis is now available to fragile X (fra[X]) syndrome families and has proven reliable when testing male fetuses. It has been reported that approximately one‐third of heterozygous fra(X) females demonstrate mental impairment. Based on this, families usually continue pregnancies involving a female fetus. The purpose of this study is to investigate whether a 35% risk for mental impairment is appropriate when counseling heterozygous women carrying fra(X)‐positive female fetuses. Forty‐three cytogenetically positive (≥2%) daughters of known fra(X) carrier women were ascertained postnatally in an unbiased fashion. Their mother's carrier status was determined on the basis of at least one son with Martin‐Bell syndrome. In addition to peripheral blood cytogenetic studies, all daughters had cognitive testing to determine full‐scale IQ. In this study, 55.8% (24/43) were mentally impaired (IQ <85) compared with the expected 35%. Of these, 42% were mentally retarded (IQ <70). Although we do not know the correlation between percent fragility by peripheral blood compared with the percent fragility by amniocentesis or CVS, we assume that they are relatively comparable such that a female who is positive with ≥2% fragility would probably be positive by all methods. This report suggests that the penetrance of mental impairment in females with a percent fragility of ≥2% may be as high as 55%. Further studies are necessary to clarify this issue so that accurate information can be given in genetic counseling.
Interstitial 15q deletion without a classic Prader‐Willi phenotype
Authors: Galán Francisco , Aguilar María Soledad , González Juan , Clemente Fernando , Sánchez Rafael , Tapia Manuel , Moya Manuel
Published: June 2005

We report on a newborn boy with pronounced hypotonia, cryptorchidism, minor facial anomalies, congenital heart defect, neurologic anomaly, deafness, renal anomaly, and bifid uvula. The patient has a de novo proximal interstitial deletion of chromosome 15 reaching to band q14, larger than that usually seen in Prader‐Willi and Angelman syndromes.
The cardio‐facio‐cutaneous (CFC) syndrome and Noonan syndrome: Are they the same?
Authors: Fryer A. E. , Holt P. J. , Hughes H. E.
Published: June 2005

The distinction between the cardio‐facio‐cutaneous syndrome (CFC) and the Noonan syndrome (NS) has been based on the presence of a characteristic facies, abnormal hair and skin, and sporadic occurrence. However, all reports of the CFC syndrome comment on the similarity between it and NS, and its sporadicnature is now debatable. This report demonstrates the evolution of the clinical phenotype in a patient with the CFC syndrome and prompts us to question the validity of separating CFC from NS.
Prevalence study of Rett syndrome in North Dakota children
Authors: Burd Larry , Vesley Barbara , Martsolf John T. , Kerbeshian Jacob
Published: June 2005

Service providers for children in the state of North Dakota were surveyed to determine the prevalence rate of Rett syndrome (RS). Five patients with definite RS were identified in a population of 203,801 children (98,932 girls) 0–18 years of age yielding a prevalence rate of RS of 1 in 40,760 in North Dakota children. For girls the rate of RS is 1 in 19,786. Similar surveys of other states using comparable modes of ascertainment will be important as points of comparison for prevalence rates of RS.
Renal and skin involvement in a patient with complete Kearns‐Sayre syndrome
Authors: Mori Kazuhiro , Narahara Kouji , Ninomiya Shinsuke , Goto Yu‐ichi , Nonaka Ikuya
Published: June 2005

We report on a 13‐year‐old girl with complete Kearns‐Sayre syndrome (KSS) and unusual manifestations of anhidrosis and de Toni‐Fan‐coni‐Debré syndrome which preceded by several years the onset of KSS triad. Histochemical examination of skeletal muscle showed focal deficiency of cytochrome c oxidase (CCO). Southern blot analysis of mito‐chondrial DNA (mtDNA) demonstrated a deletion of 5.4 kb in 60% of the total mtDNAs isolated from the muscle and kidney. On electron microscopy, epithelial cells of the proximal and distal renal tubules and the sweat glands showed an increased number of giant mitochondria with complicated and concentric cristae. This appears to be the first report of complete KSS associated with renal and skin involvement. Data obtained in this patient provide important information on the clinical heterogeneity and tissue specificity of CCO deficiency.
Generalized enchondromatosis in a boy with only platyspondyly in the father
Authors: Halal Fahed , Azouz E. Michel
Published: June 2005

We report on a boy with platyspondyly and metaphyseal manifestations of enchondromatosis with severe involvement of hands and feet, compatible with generalized enchondromatosis (enchondromatosis Spranger type VI). His father has only moderate platyspondyly. The latter is either coincidental or a milder, more localized expression of the disease. Father and son have consanguineous parents suggesting autosomal recessive inheritance of the trait. However, autosomal dominant inheritance with variable expressivity is also possible.
DNA polymorphisms and deletion analysis of the Duchenne–Becker muscular dystrophy gene in the chinese
Authors: Soong Bing‐Wen , Tsai Ting‐Fen , Su Chume‐Hwae , Kao Ko‐Pei , Hsiao Kwang‐Jen , Su Tsung‐Sheng
Published: June 2005

In our investigation of Duchenne muscular dystrophy (DMD)–Becker muscular dystrophy (BMD)gene in the Chinese, the analysis of relevant restriction fragment length polymorphisms (RFLPs) was first made in 30 normal female volunteers to determine their allele and genotype frequencies, and then in 29 DMD–BMD families for informativeness of different combinations of RFLPs in making carrier detection and prenatal diagnosis. We further screened the mutant gene, first with four 5' end intronic, genomic probes (pERT87‐1, pERT87‐8, pERT87‐15, and XJ1.1) which did not show any deletions, and then with all dystrophin cDNA probes which disclosed 13 partial gene deletions out of 29 patients studied (45%). The deletions were non‐randomly distributed, clustering primarily near the central region of the gene. Fifty percent of the deletions involved single exon‐containing HindIII restriction fragments, and again most were located near the center of the gene, emphasizing the importance of this area. Some exceptions were found against the previous suggestion that intactness of translational open reading frame resulted in a BMD phenotype. Neither the location of the break‐points nor the length of the deletions was useful in predicting a certain phenotype. One of our patients had an intriguing pattern of partial gene deletion that lost part of the gene at the 3' end. Carrier determination was attempted by use of dosage analyses or identification of junction fragments which greatly improved accuracy and reliability.
Tetrasomy of the short arm of chromosome 9: Prenatal diagnosis and further delineation of the phenotype
Authors: Schaefer G. Bradley , Domek David B. , Morgan Mark A. , Muneer Razia S. , Johnson Sarah F.
Published: June 2005

A fetus with multiple malformations was identified by prenatal ultrasound investigation. Cordocentesis and fetal lymphocyte chromosome analysis demonstrated a modal number of 47 chromosomes. The extra chromosome material was identified as an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm [47, XY, + i(9p)]. This represents the first report of prenatal diagnosis of tetrasomy 9p. Further delineation of the phenotype is discussed.
Carrier detection and prenatal diagnosis of Pelizaeus‐Merzbacher disease using a combination of anonymous DNA polymorphisms and the proteolipid protein (PLP) gene cDNA
Authors: Bridge Peter J. , MacLeod Patrick M. , Lillicrap David P.
Published: June 2005

We report carrier identification and a prenatal diagnosis using DNA polymorphisms in 2 families with X‐linked Pelizaeus‐Merzbacher disease (PMD). In both families, the proteolipid protein (PLP) gene in the single affected male could be traced back to his unaffected maternal grandfather. Therefore, each family contains a new mutation. In the case of the prenatal diagnosis, the fetus was shown by cytogenetic analysis to be a female, who we predict will be a noncarrier of PMD based on her genotype with the PLP intragenic polymorphism.
Epidemiological aspects of Mendelian syndromes in a spanish population sample: I. Autosomal dominant malformation syndromes
Authors: Martínez‐Frías M. L. , Cereijo A. , Bermejo E. , López M. , Sánchez M. , Gonzalo C.
Published: June 2005

Using a sample of 710, 815 liveborn infants throughout Spain, monitored from April, 1976, to December, 1988, by the Spanish Collaborative Study of Congenital Malformations (ECEMC), we estimated the prevalence of each recognized autosomal dominant malformation syndrome for a total prevalence figure of 12.1 per 100,000 live births, including all detected autosomal dominant malformation syndromes. We estimated that the mutation rate for those syndromes was 48.5 per 1,000,000 gametes. The geographical distribution of these syndromes was homogeneous in the Spanish Regions.
Epidemiological aspects of Mendelian syndromes in a Spanish population sample: II. Autosomal recessive malformation syndromes
Authors: Martínez‐Frías M. L. , Bermejo E. , Cereijo A. , Sánchez M. , López M. , Gonzalo C.
Published: June 2005

From April, 1976, to December, 1988, the Spanish Collaborative Study of Congenival Malformations (ECEMC) monitored a total population of 710, 815 liveborn infants in 16 of 17 Spanish Regions and identified 14, 439 (2.0%) with congenital defects. Among the malformed children, we identified 73 with well recognized autosomal recessive syndromes, for an overall prevalence rate of 10.3 per 100, 000 livebirths and a total carrier frequency of 1/49. Considering the Spanish Regions (Comunidades Autónomas), we analyzed the geographical distributions of these syndromes that were homogeneous. We studied the place of birth of the grandparents to determine the distribution of the gene as well as the gene flow.
Metaphyseal anadysplasia: A metaphyseal dysplasia of early onset with radiological regression and benign course
Authors: Maroteaux Pierre , Verloes Alain , Stanescu Victor , Stanescu Ritta
Published: June 2005

We report on 4 boys (including 2 maternally related first cousins) with a metaphyseal dysplasia of early onset and regressive evolution. Diagnosis is possible in the first months. Distal metaphyses of long bones are very irregular. Femoral necks seem hypoplastic and the edges of the metaphyses are almost vertical; femoral shaft is bowed. Those anomalies disappear after 2 years. The main manifestations are slight shortness and a light varus deformity of the lower limbs. Stature is not affected. The upper tibial growth cartilage, studied in one case, showed wide proliferative and hypertrophic zones with an unusual appearance of the last hypertrophic cells and an abnormal zone of cartilage calcification and resorption. The name “metaphyseal anadysplasia” is suggested for this early and regressive disorder. We are aware of other forms of regressive metaphyseal dysplasia which deserve further delineation. Therefore infants whose radiological changes of metaphyseal dysplasia do not fall into one of the well‐defined types should be followed and prediction of the adult height should not be made on the basis of the findings on the initial examination.
Holoprosencephaly in a newborn girl with 46,XX,i(18q)
Authors: Spinner Nancy B. , Eunpu Deborah L. , Austria Jocelyn R. , Mamunes Peter
Published: June 2005

We report on a newborn girl with holoprosencephaly, microcephaly, absent right radius, and other anomalies with an 46, XX,i(18q) chromosome constitution. This is the first report of an i(18q) in syndromal alobar holoprosencephaly.
Lethal congenital muscular dystrophy with cataracts and a minor brain anomaly: New entity or variant of Walker‐Warburg syndrome?
Authors: Wargowski David S. , Chitayat David , Tyson R. Wes , Norman Margaret G. , Friedman J. M.
Published: June 2005

A term newborn male with severe hypotonia and contractures was found to have dense bilateral cataracts. He died at age 3 days of respiratory failure. Amino acidopathies and disorders of peroxisome function were excluded, and results of serologic studies and placental histopathology, specifically seeking evidence of intrauterine infection, were normal. Autopsy showed changes in the skeletal muscles consistent with congenital muscular dystrophy and a small focal anomaly of the cerebral cortex. These findings either represent a new syndrome or raise further questions about broadening the spectrum of known congenital muscular dystrophy syndromes with associated eye and brain anomalies.
Sirenomelia and anencephaly
Authors: Rodríguez José Ignacio , Palacios José , Razquin Socorro
Published: June 2005

We report on a monozygotic twin with sirenomelia and anencephaly. This association seems to have been observed only twice before. In addition to these anomalies the patient had cleft palate, rachischisis, and segmentation vertebral anomalies affecting the cervical and the upper thoracic spine. The second twin was a liveborn female infant with a large cystic paraovarian teratoma, and duplication of internal genitalia.
Bartsocas‐Papas syndrome: Three familial cases from Spain
Authors: Martínez‐Frías M. L. , Frías J. L. , Vazquez I. , Fernández J.
Published: June 2005

We report on 3 Spanish sibs with the Bartsocas‐Papas syndrome. This appears to be the seventh reported family; all but one of them are of Mediterranean origin. We propose that a generalized vascular disruption is the most likely pathogenetic mechanism for the anomalies found in this syndrome.
Prenatal diagnosis of 48,XYY, + 21 ascertained through ultrasound anomalies
Authors: Gollop Thomaz Rafael , Naccache Nadyr F. , Auler‐Bittencourt Eloisa , Hauschild Decio , Eigier Alberto , Zveibil Deborah K.
Published: June 2005

During a routine ultrasound study on a fetus at 21 weeks, nuchal edema was noted. At 21 weeks, repeat ultrasound study at our unit showed scalp and neck edema and a femur length/biparietal diameter ratio below the mean. Transabdominal chorionic villus sampling identified a 48.XYY, + 21 chromosome constitution. The fetus had normal internal/external genitalia and signs of Down syndrome.
Teebi hypertelorism syndrome (brachycephalofrontonasal dysplasia) in a U.S. Family
Authors: Stratton Robert F.
Published: June 2005

Teebi (Am J Med Genet 28:581–591, 1987) described a pattern of anomalies in an Arab kindred involving 16 individuals in 4 generations. Although some findings were similar to those in craniofrontonasal dysplasia, absence of craniosynostosis, normal to slightly broad nasal tip, normal nails, and male to male transmission distinguished this as a separate entity. This paper describes a U.S. family with similar findings, involving 6 individuals (2 male and 4 female) in 4 generations, with male to male transmission.
Mother and son with deletion of 3p25‐pter
Authors: Tazelaar J. , Roberson J. , Van Dyke D. L. , Babu V. R. , Weiss L.
Published: June 2005

We report on a mother and son with a 3p25‐pter deletion. Both have postnatal growth retardation, mental retardation, apparently low‐set or malformed ears, and telecanthus. The mother also has ptosis and multiple joint pains, while the son has a long philtrum and anteverted nares. These phenotypes are compared to those of other 3p‐ patients. Both patients have many manifestations previously described. The son appears to be more severely affected than the mother.
Familial dermographism
Authors: Jedele Kerry B. , Michels Virginia V.
Published: June 2005

Urticaria in response to various physical stimuli has been reported in sporadic and familial patterns. The most common of these physical urticarias, dermographism, is a localized urticarial response to stroking or scratching of the skin and has not been reported previously to be familial. A four‐generation family with dermographism, probably inherited as an autosomal dominant trait, is presented along with a discussion of sporadic dermographism and other types of familial physical urticarias.
Dandy–Walker malformation in the Meckel syndrome
Authors: Herriot Richard , Hallam Lavinia A. , Gray Elizabeth S.
Published: June 2005

The Meckel syndrome is an autosomal recessive condition and includes a heterogeneous group of CNS malformations, most frequently occipital encephalocele. We report on 2 sibs and one other unrelated case with Meckel syndrome in whom the CNS anomaly was the Dandy–Walker malformation, an association not previously described. The criteria used to diagnose the Meckel syndrome are also reviewed.
Using OMIM (On‐line Mendelian Inheritance in Man) as an expert system in medical genetics
Authors: Schorderet Daniel F.
Published: June 2005

Expert systems have been used in Medicine for many years, but they are usually highly sophisticated and not well integrated into day‐to‐day practice. On the other hand, bibliographic databases suoh as Medline and others are easily accessible and are widely used. We report here the use of OMIM (On‐line Mendelian Inheritance in Man), one of these bibliographic databases, as an expert system in Medical Genetics. The description of 93 syndromes was used as search‐key and the diagnoses proposed by OMIM were analyzed to determine whether the correct diagnosis was among them. The proposed diagnoses were automatically ranked by OMIM from the most probable (weight = 100) to the least probable (weight = 1). OMIM suggested a total of 1538 +/− 692.2 diagnoses per search. In order to deal with a reasonable number of proposed diagnoses, we only considered the diagnoses with a weight of 50 or more. With this limit, OMIM proposed a mean of 37.0 +/− 24.6 diagnoses per case. The overall accuracy was 76%. A correct answer with a perfect weight of 100 was proposed in 29% of the cases. The diagnostic accuracy of OMIM increased linearly when weights lower than 100 were considered. When the rank alone was analyzed, the accuracy of OMIM increased very rapidly from position 1 to 5 with a subsequent almost linear increase. If one only considered the first five proposed diagnoses, the accuracy of OMIM was just above 50%.

This study shows that bibliographic databases are not only restricted to the provision of references but could also be used as expert systems and are therefore of great value to medical geneticists.
Dandy‐Walker malformation (variant), cystic dysplastic kidneys, and hepatic fibrosis: A distinct entity or Meckel syndrome?
Authors: Walpole Ian R. , Goldblatt Jack , Hockey Athel , Knowles Simon
Published: June 2005

Dandy‐Walker malformation is an unusual finding in Meckel syndrome, which characteristically presents with encephalocele, polydactyly, and cystic renal disease. We report on a family in which three nonviable brothers had Dandy‐Walker malformations (variant) with associated enlarged cystic dysplastic kidneys and hepatic fibrosis. The consistent segregation of these abnormalities in all three sibs in the absence of polydactyly and encephalocele suggested the possibility of a distinct syndrome. The clinicopathological findings of the disorder are described and discussed in the context of the phenotypic spectrum of Meckel syndrome.
Syndrome: Le Mot de Jour
Authors: Jablonski Stanley
Published: June 2005

Syndrome is one of the oldest terms in the medical vocabulary. It has been used as a designation for those disorders that were marked by etiologically nonspecific similar groups of manifestations up to the time of Sydenham. His contention that the terms syndrome and disease were in fact synonymous explains in part infrequent use of syndrome in the literature until the latter part of the 19th century. Redefinition of syndrome early in the 20th century as a disorder characterized by the concurrence of symptoms which are causally related, and further refinement of the definition as a condition marked by a cluster of symptoms occurring together coincidentally, gradually restored the popularity of the term to where syndrome is now one of the most frequently used designations of morbid states in the literature. There are numerous definitions of syndrome currently in use. One which is accepted by most dysmorphologists, geneticists, and some clinicians states that syndrome is an etiologically defined entity of unknown pathogenesis. However, most writers use the term randomly to denote any abnormal condition, whether medical, social, or behavioral, when a more satisfactory designation cannot be found or created, or to emphasize special complexity (syndromic qualities?) of already named diseases, or merely to be amusing. The post‐Sydenham custom of naming of syndromes after physicians gave way in the mid‐20th century to methods wherein syndrome names incorporate clinical, etiological, genetic, and other significant characteristics. Other methods used in designating syndromes include using the names of the first patient known to be affected, acronyms and abbreviations, personal names of all kinds, and the like. Syndrome, once a unique and valuable term in the arsenal of medical vocabulary, has lost much of its usefulness through misuse.
Duty to disclose in medical genetics: A legal perspective
Authors: Pelias Mary Z.
Published: June 2005

As technical knowledge and public information in medical genetics continue to expand, the geneticist may expect to be held responsible for informing patients and clients about new developments in research and diagnosis. The long legal evolution of the physician's duty to disclose, and more recent findings of a physician's duty to recall former patients to inform them about newly discovered risks of treatment, indicate that medical geneticists may have a duty to disclose both current and future information about conditions that are or could be inherited. Recent case law supports findings of professional liability for both present and future disclosure, even in the absence of an active physician‐patient relationship. The requirement of candid and complete disclosure will affect the counseling approach in testing for deleterious genes and in providing medical treatment for minors with hereditary diseases. Finding a duty to recall may impose further professional burdens on the geneticist to reach beyond the immediate counseling arena and to recontact patients, perhaps years after their initial visit to genetics clinic.
Sir A.E. Garrod, congenital heart disease in Down syndrome, and the doctrine of fetal endocarditis
Authors: Lubinsky Mark S.
Published: June 2005

Archibald Garrod was apparently the first to document congenital heart disease as a component of Down syndrome. This arose from his interest in fetal endocarditis, a theoretical cause of cardiac malformations, in vogue roughly from 1840–1940, that drew its strength from analogies with rheumatic heart disease in adults. Garrod's discovery sheds light not only on nineteenth century ideas about teratology, but also on his methodology, genius, and approaches that, in many ways, foreshadowed the techniques that guided his later work on inborn errors.
Autosomal recessive Peters anomaly, typical facial appearance, failure to thrive, hydrocephalus, and other anomalies: Further delineation of the Krause‐Kivlin syndrome
Authors: Frydman Moshe , Weinstock Arie L. , Cohen Herman A. , Savir Hanna , Varsano Itzhak
Published: June 2005

Two cousins and an unrelated patient, all offspring of consanguineous parents, presented with Peters anomaly, unusual facial appearance, disproportionate short stature, retarded skeletal maturation, and a variable degree of mental retardation. Variable digital, cardiac, CNS, and urogenital anomalies were present. The inheritance is probably autosomal recessive. The condition is a distinct clinical entity for which we suggest the eponym Krause‐Kivlin syndrome. Peters anomaly is thought to result from abnormal migration of neural crest cells. A similar mechanism was implicated in the pathogenesis of other disorders of the anterior chamber. The presence of Peters anomaly, and possibly of other corneal endothelial disorders in a newborn infant, should alert the clinician to the possibility of this syndrome. Communicating hydrocephalus (or brain atrophy) and polyhydramnios were documented in two patients, potentially allowing prenatal diagnosis in secondary familial cases.
Inversion‐duplication of bands q13→q21 of human chromosome 9
Authors: Luke Sunny , Verma Ram S. , Pebenito Rhandy , Macera Michael J.
Published: June 2005

Structural abnormalities involving heterochromatic regions of the human genome are difficult to characterize because these segments are G‐band negative by GTG technique, a routinely used procedure in clinical cytogenetic laboratories. Chromosome abnormalities of such cases have gone undetected or were incorrectly characterized because these regions are so‐called heteromorphisms or variants. Consequently, much anxiety has been aroused by the confusion between a chromosome abnormality and a normal heteromorphic variant. We report the first documented case with a so‐called highly unusual h region of chromosome 9 which is not a variation but a structural rearrangement involving a paracentric inversion and a duplication. The major clinical features were psychomotor retardation, microcephaly, narrow palpebral fissures, renal and genital anomalies, vertebral anomalies, protruding tongue, and learning and behavioral problems. A concise review of variable duplicated segments of 9q is also provided.
Waardenburg I syndrome: A clinical and genetic study of two large Brazilian kindreds, and literature review
Authors: Da‐Silva Elias O.
Published: June 2005

Two large kindreds with Waardenburg I syndrome are described. The total number of affected individuals is 73. The major manifestations are telecanthus (the only constant anomaly in all cases), prominent nasal root, round or square tip of nose, hypoplastic alae, smooth philtrum, bushy eyebrows with synophrys, sensorineural deafness, heterochromia or hypoisochromia iridis, hypopigmented ocular fundus, white forelock, premature greying, and hypopigmented skin lesions. These and other aspects of the syndrome, associated findings, frequency, genetic heterogeneity, pathogenesis, animal models, and gene linkage and mapping are reviewed briefly.
Patient with multiple congenital anomalies and decreased production and processing of procollagen in cultured fibroblasts
Authors: Pavone L. , Incorpora G. , Fiumara A. , Sorge G. , Ramirez F. , McGarry J. , Wootten J. , Minor R.
Published: June 2005

We report on a patient with hip and elbow dislocations, joint hyperextensibility, peculiar facial appearance, torticollis, cryptorchidism, unilateral hexadactyly, and other minor anomalies. Cultured cells from this patient produce less type I procollagen and have a slower rate of processing of type I procollagen to collagen in the culture medium. We think that the pattern of clinical anomalies constitutes a previously unreported syndrome with type I procollagen defect as a manifestation of the syndrome.
Holoprosencephaly as a possible embryonic alcohol effect
Authors: Ronen Gabriel M. , Andrews Wayne L.
Published: June 2005

Three mothers of infants with holoprosencephaly consumed alcohol heavily in pregnancy. We postulate that early alcohol exposure is a possible cause of their malformation. The 3 mothers consumed alcohol only in the first trimester but the first mother continued to take chlordiazepoxide and imipramine throughout the pregnancy. Her infant had an alobar holoprosencephaly associated with a median cleft lip, ocular hypotelorism, and a flat nose. The other infants had semilobar holoprosencephaly and hydrocephalus. These latter 2 infants did not show the characteristic facies of the fetal alcohol syndrome. G‐band chromosome studies were normal in all 3 infants. The association of holoprosencephaly with alcohol exposure during pregnancy in humans has been mentioned only briefly, although this malformation has been induced by alcohol in animals. These 3 infants may support the hypothesis that acute or subacute heavy alcohol exposure early in pregnancy could lead to holoprosencephaly without the necessity of a chronic alcohol exposure and without necessarily causing the typical facial findings of the fetal alcohol syndrome.
Noonan‐like/multiple giant cell lesion syndrome
Authors: Cohen M. Michael , Gorlin Robert J.
Published: June 2005

A patient with the Noonan‐like/multiple giant cell lesion syndrome is reported and the findings in 14 cases are reviewed. Impressive manifestations include short stature, low normal intelligence or developmental delay, ocular hypertelorism, prominent posteriorly angulated ears, giant cell lesions of bones, joints, and/or soft tissues, pectus excavatum, and pulmonic stenosis. It has been difficult to delineate the syndrome because problems in identifying the condition have resulted from incomplete or truncate ascertainment by various medical specialists.
Apparent Opitz BBBG syndrome with a partial duplication of 5p
Authors: Leichtman Lawrence G. , Werner Alice , Bass W. Thomas , Smith Deborah , Brothman Arthur R.
Published: June 2005

We describe a patient with a paracentric inversion and partial duplication of chromosome 5p. In addition this patient presented with a malformation pattern consistent with Opitz BBBG syndrome. This implies that the gene responsible for this single gene defect may be located within this duplicated region.
Familial holoprosencephaly associated with a translocation breakpoint at chromosomal position 7q36
Authors: Hatziioannou Androniki G. , Krauss Celeste M. , Lewis Michael B. , Halazonetis Thanos D.
Published: June 2005

A familial balanced t(7;9) (q36;q34) was reported recently. Analysis of the craniofacial features of 3 of the sibs showed signs of holoprosencephaly. Two ofthe sibs have an unbalanced derivative chromosome leading to del(7) (q36) and dup(9) (q34), while the other has a cytogenetically balanced translocation. These findings, together with several reports associating holoprosencephaly with terminal 7q deletions, indicate that a putative locus for holoprosencephaly resides at or near 7q36. It should now be feasible to clone this locus.
Short rib syndrome—Beemer type in sibs
Authors: Hennekam Raoul C. M.
Published: June 2005

The short rib (polydactyly) syndrome Beemer type is a rare lethal osteochondrodysplasia characterized clinically by short limbs, median cleft upper lip and palate, narrow thorax, and protuberant abdomen, and radiologically by short ribs, short and bowed long bones, and mild platyspondyly. Two affected female sibs are described, one having a preaxial polydactyly of the feet. The differentiation with the short rib syndrome Majewski type relies mainly on the radiological appearance of the tibia. Molecular biology may eventually prove whether the 2 conditions are truly separate entities or not.
Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families
Authors: Cianchetti Carlo , Sannio‐Fancello Giuseppina , Fratta Anna‐Lisa , Manconi Francesco , Orano Ada , Pischedda Maria‐Paola , Pruna Dario , Spinicci Gabriella , Archidiacono Nicoletta , Filippi Giorgio
Published: June 2005

One hundred forty‐nine subjects from 18 families with fragile X [fra(X)] syndrome were evaluated for their neuropsychological, psychiatric, and physical characteristics. The 36 fra(X) males had intelligence quotients ranging from < 20 to 61, which prevented the delineation of a reliable neuropsychological profile. Behaviour fitted DSM‐III‐R and ADI diagnostic criteria of autism in only 2 subjects, both with very low intelligence level (IQ < 20). Of 36 heterozygotes (HZ), 22 had an IQ between 20 and 80 and 14 between 81 and 99. The neuropsychological profile of the latter was compared with IQ‐age‐environmentmatched 14 normal females and 14 normal males. Significantly poorer results in HZ were found on immediate digit memory and on Raven's progressive matrices (a visuo‐spatial test of logical capabilities). The latter result, in conjunction with those results on the Bender visual‐motor gestalt test and on some WAIS subtests, suggests a frequent deficit in spatial capabilities in such subjects. Such results tended to be confirmed by the profiles of the 22 HZ with IQ 20‐80. No psychiatric abnormalities were found in HZ, except in one subject with IQ < 20 which fitted DSM‐III‐R and ADI criteria for autism. Typical physical manifestations, especially cranio‐facial, were more frequently present in the HZ group with lower IQ. Subnormal IQ was probably the most reliable abnormality for the detection of HZ in 49 females at 50% and 25% risk of heterozygosity.
Keratitis, hepatitis, ichthyosis, and deafness: Report and review of KID syndrome
Authors: Wilson Golder N. , Squires Robert H. , Weinberg Arthur G.
Published: June 2005

A 14‐year‐old girl with ichthyosis and severe liver disease is compared to 35 reported cases of KID or Senter syndrome. Common manifestations such as ichthyosis (35/35 patients), sensorineural deafness (33/34), “ectodermal dysplasia” (25/28), corneal abnormality (26/31) were present in the proposita, while less common manifestations such as chronic infections (15/20) and neuromuscular disease (12/35) were absent. Two families with vertical transmission and 28 sporadic cases are compatible with an autosomal dominant form of KID syndrome, while one inbred sibship with liver disease suggests the existence of an autosomal recessive form. The proposita was similar to the latter patients in having progressive cirrhosis necessitating liver transplantation; she also had short stature (10/35 patients) and mental retardation (3/35). Hepatic findings included micronodular cirrhosis, cholestasis, hyperplastic Kupffer cells, abundant Mallory's hyaline, copper accumulation without steatosis, and normal peroxisomes.
Jarcho‐Levin syndrome: Four new cases and classification of subtypes
Authors: Karnes Pamela S. , Day Deborah , Berry Susan A. , Pierpont Mary Ella M.
Published: June 2005

The Jarcho‐Levin syndrome is a condition manifested by vertebral body and related rib malformations. We report on four new cases and review 57 cases from the literature. Analysis of the 61 cases suggests that there are two major subtypes (spondylocostal dysostosis and spondylothoracic dysostosis) with different survival rates, associated malformations, and inheritance patterns. Individuals with spondylothoracic dysostosis have vertebral body malformations and ribs which flare in a fanlike pattern but which are not significantly malformed. This is an autosomal recessive trait, and the patients have a higher mortality rate and greater incidence of neural tube defects. Individuals with spondylocostal dysostosis have vertebral malformations, frequent dramatic rib malformations, and short stature, but do not have a fanlike thoracic configuration. Most cases of spondylocostal dysostosis are inherited in an autosomal recessive fashion, although in a few families it is a dominant trait which is correlated with better survival. Respiratory compromise previously accounted for the high mortality in these conditions, but improvements in respiratory technology have increased survival. Appropriate classification of these similar phenotypes will improve counseling concerning recurrence risk, management, and prognosis.
Oculocerebrocutaneous (Delleman) syndrome: A pleiotropic disorder affecting ectodermal tissues with unilateral predominance
Authors: Hoo Joe J. , Kapp‐Simon Kathleen , Rollnick Beverly , Chao Margaret
Published: June 2005

We present a patient with oculocerebrocutaneous syndrome. The boy shows only mild psychomotor delay in spite of rather severe appearing anomalies of the central nervous system. A primarily unilateral involvement of this syndrome is emphasized. A postzygotic/somatic mutation resulting in a mosaic state might account for the primarily ectodermal involvement, the unilateral predominance, and the sporadic nature of this syndrome. An alternative hypothesis of an environmental factor might also explain the clinical manifestations of the syndrome.
Spondylo‐metaphyseal dysplasia Algerian type: Confirmation of a new syndrome
Authors: Rybak M. , Foley T. P. , Kozlowski K.
Published: June 2005

We report on a further case of a recently described type of spondylo‐metaphyseal dysplasia in a 1210/12‐year‐old Polish boy. The original paper described the disorder in five relatives in an Algerian family.
Triple autosomal trisomy in a pregnancy at risk for Bloom's syndrome
Authors: Petrella Rena , Hirschhorn Kurt , German James
Published: June 2005

Cytogenetic analysis of the products of conception in a pregnancy at risk for Bloom's syndrome (BS) documented the karyotype 49,XX, + 2, + 8, + 11. Autosomal triple trisomy has previously been reported in abortuses but is exceedingly rare. Other interesting but previously unreported observations made during the present study were the following: BS in a Brazilian individual, the first instance of BS diagnosed in South America; transmission of the BS mutation in Jews that are non‐Ashkenazi; a medulloblastoma in the propositus, the first malignant brain tumor reported in BS; and, as in all previously examined pregnancies at risk for BS, non‐homozygosity for the BS mutation.
Cataracts, aberrant oral frenula, and growth retardation: A new autosomal dominant syndrome
Authors: Wellesley Diana , Carman Paul , French Noel , Goldblatt Jack
Published: June 2005

We report on a mother and her two children with an autosomal dominant cataract syndrome with associated aberrant oral frenula, growth retardation, and specific facial appearance. Their phenotype differs from that of other reported cataract syndromes, and we conclude that this is a previously undescribed entity.
Delayed spontaneous pubertal growth spurt in girls with the Ullrich‐Turner syndrome
Authors: Pelz Lothar , Sager Günther , Hinkel Georg Klaus , Kirchner Margitta , Krüger Gabriele , Verron Günther
Published: June 2005

By means of an appropriate mathematical model (Sager's 2‐components‐concept) a delayed spontaneous pubertal growth spurt can be demonstrated in girls with 45, X Ullrich‐Turner syndrome (UTS) (n1 = 45) as well as in those with 45, X/46,XX mosaicism (n2 = 14) never treated with any growth stimulating drug. On the average, this growth spurt begins later and its extent is smaller (mean growth rate = 3.10 and 2.79 cm, respectively, in the 15th year of chronological age) than in normal girls. The delay in acute growth spurt corresponds very well to the delay of skeletal maturation in the UTS (on the average 2 to 3 years of chronological age).
Dominantly inherited syndrome comprising partially absent eye muscles, hydrocephaly, skeletal abnormalities, and a distinctive facial phenotype
Authors: Chitty Lyn S. , McCrimmon Rory , Temple I. Karen , Russell‐Eggitt Isobel M. , Baraitser Michael
Published: June 2005

We report on an autosomal dominant syndrome comprising partially absent eye muscles, anterior chamber defects, hydrocephalus, skeletal changes, and a specific facial phenotype.
Hepatic dysfunction in Alström disease
Authors: Connolly Mary B. , Jan James E. , Couch Robert M. , Wong Lawrence T. K. , Dimmick James E. , Rigg J. Michael
Published: June 2005

Alström disease is a rare disorder; less than 20 cases have been reported. An 11‐year‐old girl is described with this condition. She has pigmentary retinopathy, sensory neural deafness, obesity, Type II diabetes mellitus, hyperlipidemia, and acanthosis nigricans. However, in addition she developed hepatic dysfunction, pathologically similar to chronic active hepatitis. This may be a further, previously undescribed systemic manifestation of Alström disease.
Opitz trigonocephaly syndrome
Authors: Haaf Thomas , Hofmann Renate , Schmid Michael
Published: June 2005

We report on a patient with Opitz trigonocephaly syndrome. The girl was the firstborn child of consanguineous parents and had trigonocephaly, apparent hypertelorism, upslanted palpebral fissures, strabismus, small nose with broad root, abnormally modeled ears, high palate, short neck with loose skin, polysyndactyly, and prominent clitoris and labia majora. In addition, a complex cardiovascular defect (Eisenmenger disease) was observed. The patient was mentally retarded.
Ring chromosome 15 and 15qs+ mosaic: Clinical and cytogenetic behaviour spanning 29 years
Authors: Smith Arabella , den Dulk Gesina , Viersbach Renate , Michas John
Published: June 2005

A phenotypic female with mild mental retardation, minor facial anomalies, and short stature has been evaluated clinically and cytogenetically over 29 years. At age 59, she remains physically well and shows no signs of dementia. Cytogenetic analysis, performed on peripheral blood specimens on 10 occasions between 1961 and 1990, showed mosaicism with one cell line containing a large stable ring (15) chromosome and another cell line without the ring but with a 15qs +. The different cell lines remained constant. The case provides information on the natural history of the ring chromosome 15 syndrome.
Trisomy 9 confined to the placenta: Prenatal diagnosis and neonatal follow‐up
Authors: Appelman Z. , Rosensaft J. , Chemke J. , Caspi B. , Ashkenazi M. , Mogilner M. B.
Published: June 2005

Chorionic villus sampling (CVS), performed on a woman in the 23rd menstrual week because of bilateral fetal hydronephrosis and suspected intrauterine growth retardation (IUGR), documented trisomy 9 in all cells examined. Chromosomes of amniocytes and fetal blood lymphocytes were normal. The ongoing pregnancy was monitored closely, and at 37 weeks, a phenotypic normal male infant was delivered. Multiple placental biopsies showed 47,XY,+9, while a repeat chromosome analysis of the infant and biopsies from the amniotic membrane were normal (46,XY). This case further emphasizes the association between placental aneuploidy and IUGR. To our knowledge, nonmosaic trisomy 9 in CVS confined to the chorionic villi and later confirmed in the placenta has not been reported previously.
San Luis Valley Recombinant chromosome 8 and tetralogy of Fallot: A review of chromosome 8 anomalies and congenital heart disease
Authors: Gelb Bruce D. , Towbin Jeffrey A. , McCabe Edward R. B. , Sujansky Eva
Published: June 2005

Tetralogy of Fallot, the most common cyanotic heart defect, has not been closely associated with a specific chromosome defect. The San Luis Valley Recombinant Chromosome 8 [SLV Rec(8)] syndrome is strongly associated with congenital heart disease, particularly tetralogy of Fallot. This article reviews SLV Rec(8) syndrome and other chromosome 8 aberrations to suggest locations for cardiogenic genes.

SLV Rec(8) [rec(8), dup q,inv(8)(p23q22)] syndrome has been found in Hispanic families in the southwestern United States. Congenital heart disease is found in 93.3% of SLV Rec(8) individuals (n = 45), with tetralogy of Fallot constituting 40.5% of all lesions and conotruncal defects, 55.6%. These frequencies exceed the incidence of tetralogy of Fallot (10%) and conotruncal defects (20%) among all children with heart defects (P<0.003 for both).

Review of patients with deletion 8p (n=13) showed heart defects in 84.6% with 27.3% being conotruncal defects. Among duplication 8q patient (n = 20), 45% had heart defects with conotruncal defects constituting 44%. Neither group differed significantly from expected in its incidence of conotruncal defects. Among patients with mosaic trisomy 8 (n = 47), 12 had heart abnormalities including one conotruncal defect. Among 3 patients with other rec(8) chromosomes, one had a ventricular septal defect.

The cause of heart defects in SLV Rec(8) cannot be assigned to either the deletion of 8p or the duplication of 8q. The lack of an association between other chromosome 8 abnormalities and tetralogy of Fallot suggests that genes at the SLV Rec(8) breakpoints or an interaction between genes on both arms of chromosome 8 are important.
Absence of fetal cells in maternal circulation at a level of 1 in 25,000
Authors: Nakagome Yasuo , Seki Satoko , Nagafuchi Shigeo , Nakahori Yutaka , Sato Kodo
Published: June 2005

A dual polymerase chain reaction (PCR) technique is developed which enables the detection of one part male DNA in 25,000 parts female DNA. The technique amplifies a part of the X‐Y homologous amelogenin gene in which the Y counterpart has a 189 bp deletion within one of the introns. This deletion has made it possible to identify individual X and Y counterparts based on the difference in size between them.

None of the 18 pregnant women studied showed a positive Y‐signal although eight of them bear male fetuses excluding the presence of fetal cells at one in 25,000 maternal cells. The results presented here show that a sensitivity of greater than one in 25,000 is required for detection of fetal genetic disease using maternal peripheral blood.
Townes—Brocks syndrome in two mentally retarded youngsters
Authors: Cameron Thomas H. , Lachiewicz Ave M. , Aylsworth Arthur S.
Published: June 2005

We report on 2 children with Townes‐Brocks syndrome (TBS) and mental retardation. One child had mild hearing loss, but the other only had hearing loss at 8000 Hz. These cases suggest that there may be an increased incidence of mental retardation in individuals with TBS.