bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of X inactivation: Loss of one X inactivation center in a case with mos45,X, –21, +der(21)t(X;21) (p21.3;p11.2)/46,X,t(X;21) (p21.3;p11.2)
Authors: Ishikiriyama Satoshi , Iai Mizue , Tanabe Yuzo
Published: June 2005

We present a girl with a mos45,X, −21, +der(21)t(X;21) (p21.3;p11.2)/46,X,t(X;21) (p21.3;p11.2) chromosome constitution. The ratio of these cells was 59/26 in phytohemagglutinin (PHA)‐ stimulated lymphocytes. The 45,X,der(21) t(Xp–;21p+) cells lacked an X inactivation center located at Xq13 on the derivative X chromosome; in these cells, the whole normal X chromosome and the distal part of Xp translocated onto the derivative chromosome 21 were early replicating. She had moderate mental retardation and other findings different from those that occur in the Ullrich‐Turner syndrome. Her phenotype may be due to the functional excess of the distal part of Xp on the derivative 21 in 45,X,der(21)t(Xp–;21p+) cells; thus, this might be another type of the “lack of X‐inactivation” syndrome. © 1993 Wiley‐Liss, Inc.
Cancer in twins of Wilms tumor patients
Authors: Olson Jane M. , Breslow Norman E. , Barce Jean
Published: June 2005

We interviewed families of 71 patients registered in the National Wilms Tumor Study and identified as having a twin sibling. Questions concerning zygosity and the occurrence of congenital anomalies and other forms of cancer in the twins were asked. Of the 71 twin pairs, 35 were dizygotic, 31 were monozygotic, and 5 were of unknown zygosity. The only pair concordant for Wilms tumor was dizygotic, leading to a heritability estimate of zero. In a monozygotic pair, one twin was diagnosed with Wilms tumor and the other with medulloblastoma. The estimated relative risk of Wilms tumor and childhood cancer in the co‐twin was 250 times and 10 times the population rate, respectively. Four discordant pairs had a family history of Wilms tumor, suggesting that the penetrance of the condition is not complete. Because of the small sample size, caution should be exercised in the interpretation of these results. © 1993 Wiley‐Liss, Inc.
The Costello syndrome
Authors: Say Burhan , Güçsavaş Müge , Morgan Harley , York Cindy
Published: June 2005

In 1971 and again in 1977, Costello reported on two unrelated children with multiple congenital malformations associated with growth and developmental retardation and nasal papillomata (Costello, NZ Med J 74:397, 1971; Costello, Aust Paediatr J 13:114–118, 1977). Subsequently, two similar cases were described (Der Kaloustian et al., Am J Med Genet 41:69–73, 1991; Martin and Jones, Am J Med Genet 41:346–349,1991). Costello syndrome is now a distinct entity. We describe another patient who additionally had hitherto unreported malformations, such as hydrocephalus, seizures, atrial fibrillation, and flutter with atrial septal defect. Although no nasal lesions were found he had laryngeal papillomata associated with a congenital web. A skin biopsy showed no evidence of lipid or mucopolysaccharide storage disease and muscle biopsy was normal by gross and electron microscopic examination. © 1993 Wiley‐Liss, Inc.
Multiple meningiomas in a patient with constitutional ring chromosome 22
Authors: Petrella Rena , Levine Seymour , Wilmot Patrick L. , Ashar Kunjlata D. , Casamassima Anthony C. , Shapiro Lawrence R.
Published: June 2005

We report on a patient with multiple congenital anomalies and ring chromosome 22 who died at age 16 years of bronchopneumonia. Autopsy documented multiple psammomatous meningiomas of the spinal dura and tentorium. Tumor tissue for cytogenetic analysis was not available. Although abnormalities of chromosome 22 in tumor tissue have been reported, to our knowledge, this is only the third report of a constitutional chromosome 22 abnormality associated with the development of meningiomas. Thus, a constitutional chromosome 22 abnormality may predispose to the development of meningiomas. © 1993 Wiley‐Liss, Inc.
Adaptive behavior in the fragile X syndrome: Profile and development
Authors: Wiegers A. M. , Curfs L. M. G. , Vermeer E. L. M. H. , Fryns J. P.
Published: June 2005

In this study we present data on the adaptive behavior profile and on the development of adaptive functioning in 39 fragile X [fra(X)] males, age 4–26 years. Social adaptability is relatively well developed as compared to cognitive level and especially self‐help skills continue to grow with age despite a stagnation in intellectual growth. © 1993 Wiley‐Liss, Inc.
Hypomandibular faciocranial dysostosis: Another case and review
Authors: Ludman Mark D. , Vincer Michael J. , Cron Charles , Aguiar Maria , Cohen M. Michael
Published: June 2005

We report on a third case of hypomandibular faciocranial dysostosis and review the literature. Manifestations include craniosynostosis, prominent eyes, deficient midface and zygomatic arches, short nose with anteverted nares, protruding lower face, minute oral aperture, persistent buccopharyngeal membrane, and severe mandibular hypoplasia. In contrast to coronal synostosis found in the 2 earlier cases, our patient had multiple sutural synostosis. The 2 affected sibs reported earlier suggest the possibility of autosomal recessive inheritance. However, gonadal mosaicism for a dominant mutation or an undetected microdeletion must also be considered at this early stage in the delineation of this disorder. © 1993 Wiley‐Liss, Inc.
Isodicentric X chromosome and mosaicism: Report on two cases of 45,X/46,X,idic(Xq)/47,X,idic(Xq),idic(Xq) and review of the literature
Authors: Melaragno Maria Isabel , Fakih Laila M. A. , Cernach Mirlene C. S. P. , Maccagnan Paulo
Published: June 2005

We present 2 instances of Ullrich‐Turner syndrome with mosaicism 45,X/46,X,idic(Xq)/47,X,idic(Xq),idic(Xq) and X‐isochromosomes with 2 C‐bands. The mosaicism with the 3 cell lines point to the presence of the isodicentric chromosome in the zygote and a subsequent nondisjunction event. © 1993 Wiley‐Liss, Inc.
Congenital central hypoventilation syndrome: Inheritance and relation to sudden infant death syndrome
Authors: Weese‐Mayer Debra E. , Silvestri Jean M. , Marazita Mary L. , Hoo Joe J.
Published: June 2005

We evaluated the families of 50 children with idiopathic congenital cental hypoventilation syndrome (CCHS) to (1) test genetic hypotheses, (2) explore the relationship to Hirschsprung disease (HD), and (3) examine other clinical findings including sudden infant death syndrome (SIDS) in relatives of CCHS patients. A questionnaire was administered to parents of each proband to determine a detailed pedigree and medical history for 3 generations including 1,482 relatives. The data were analyzed under the unified mixed model method (assumes individual genotype composed of multifactorial [MF] and major locus [ML] components). Analysis was made of the Total dataset and on subdivided data sets: HIR1 = families of probands with HD (n = 8) vs. HIR2 = families of probands without HD; then under a premise that severe, chronic constipation may be a milder form of HD (i.e., ganglion cells present but dysfunctional), CON1 = families of probands with HD or constipation (n = 13) vs. CON2 = families of probands without HD or constipation. By statistical genetic analysis of the Total, HIRI, and CON1 datasets, the MF and ML hypotheses were about equally likely, with the MF model slightly more parsimonious. Although HIR2 and CON2 datasets indicated no familiality, statistical evidence of heterogeneity between the result of HIR1 and HIR2, or between CON1 and Con2 was lacking. A SIDS incidence of 11.2/1,000 was documented among the relatives of CON1 vs. 1.8/1,000 among relatives of CON2. Our results are consistent with familiality by either MF or ML models. Recurrence risk is likely <5%. The relationship of CCHS to the high familial incidence of SIDS is intriguing and demand further investigation. © 1993 Wiley‐Liss, Inc.
Diagnosis of Huntington disease: A model for the stages of psychological response based on experience of a predictive testing program
Authors: Bloch M. , Adam S. , Fuller A. , Kremer B. , Welch J. P. , Wiggins S. , Whyte P. , Huggins M. , Theilmann J. , Hayden M. R.
Published: June 2005

Persons diagnosed as affected with Huntington's disease (HD) may have similar stages of psychological response to the clinical presentation of the illness. Here we describe a model of these stages of response based on our experience during a predictive testing program for HD. During the warning Stage, asymptomatic persons are aware of their risk status for HD and develop defenses which favor adaptation to their genetic risk. In response to the initial signs and symptoms of HD (the Incipient Stage) unconscious working through of this realization occurs while it is still kept out of conscious awareness. When symptoms become obvious such that recognition of disease onset is inevitable (Break‐through Stage) the possibility of the diagnosis of HD is assimilated. After the delivery of the diagnosis during the Adjustment Stage, short‐and long‐term adaptive responses to living with HD occur.

Recognition of the stage of psychological response of a patient who presents with HD is important prior to delivering a clinical diagnosis. In a significant minority of cases, the psychological readiness lags behind the clinical symptomatology and premature presentation of diagnosis may result in significant untoward adverse events. Understanding of the stages of response may provide a frame‐work for evaluating the psychological state of the person with HD and determining their readiness to receiving the diagnosis. This model may have relevance to the psychological responses of patients to the diagnosis of other late onset autosomal dominant disorders. © 1993 Wiley‐Liss, Inc.
Thyroid dysgenesis and the dysplasia hypothesis in tuberous sclerosis
Authors: Bereket Abdullah , Wilson Thomas A.
Published: June 2005

Thyroid dysfunction is rare in tuberous sclerosis, although papillary adenomas (hamartomas) of the thyroid gland have been reported in a few autopsy cases. We describe a child with tuberous sclrosis and primary congenital hypothyroidism secondary to a dysgenetic thyroid gland. To our knowledge, this association has not been reported previously. Although the association of these two disorders in one patient may be merely coincidence, we speculate that the dysgenetic thyroid gland in this patient may represent a “hamartia” as a consequence of the tuberous sclerosis gene. © 1993 Wiley‐Liss, Inc.
Schwartz–Jampel syndrome: An atypical form?
Authors: Figuera Luis E. , Jimenez‐Gil F. Javier , García‐Cruz M. Olga , Cantú José M.
Published: June 2005

The Schwartz–Jampel syndrome (SJS) is an autosomal recessive disorder of myotonia, short stature, “mask‐like” face, blepharophimosis, stiff joints, spinal malalignment, and pectus carinatum. The authors report on a 10‐year‐old girl with expressionless face, blepharophimosis, mild thoracic asymmetry, and myotonic electromyographic pattern, but without osteoarticular, spinal, and statural involvement. This appears to be one of the mildest form of SJS described so far. Contiguous genes could be an explanation for this and other atypical cases of SJS. © 1993 Wiley‐Liss, Inc.
Leukonychia totalis in two sibs
Authors: Frydman Moshe , Cohen Hermann A.
Published: June 2005

A sister and a brother, offspring of unaffected consanguineous Arab parents, were found to have leukonychia totalis and flat, wide nails. To our knowledge this is the first report of apparent autosomal recessive transmission of this trait. A parental somatic mutation with gonadal mosaicism may explain the unusual segregation of the trait in this family. © 1993 Wiley‐Liss, Inc.
Tetrasomy 5p mosaicism in a boy with delayed growth, hypotonia, minor anomalies, and an additional isochromosome 5p [46,XY/47,XY, + i(5p)]
Authors: Sijmons Rolf H. , Leegte Beike , Van Lingen Richard A. , De Pater Joke M. , Van Der Veen Anneke Y. , Canho Harrij Del , Bos Carla , Kate Leo P. Ten , Breed Anton S. P. M.
Published: June 2005

We describe a 1‐year‐old boy with a rare de novo 46,XY/47,XY,+ i(5p) mosaicism (ratios 28/3 in peripheral blood lymphocytes and 2/12 in skin fibroblasts). The boy, born after a pregnancy of 34 weeks, had lung hypoplasia, persistent hypotonia, and postnatal growth failure. Craniofacial anomalies were also present. His clinical manifestations correspond to those described in trisomy 5p patients. Prenatal diagnosis on maternal age indication had shown normal male chromosomes in 16 cells in the short term culture of a chorionic villus sampling. Retrospectively, 1 out of 217 cells in this culture showed the i(5p). Several mechanisms could have resulted in the formation of this 46/47, + i(5p) mosaic. Postzygotic local incorrect ligation during chromatid replication, followed by a second replication offers an attractive model on theoretical grounds since it needs only one step to explain both isochromosome formation and mosaicism. Differences between the various tissues in selection pressure on cells with the isochromosome might explain the different ratios of mosaicism found. © 1993 Wiley‐Liss, Inc.
Encephalocraniocutaneous lipomatosis, Proteus syndrome, and somatic mosaicism
Authors: Rizzo Renata , Pavone Lorenzo , Micali Giuseppe , Nigro Francesco , Cohen M. Michael
Published: June 2005

We report on a patient with manifestations of encephalocraniocutaneous lipomatosis and Proteus syndrome. Further comparison with other reported patients demonstrates a continuum, not 2 distinct entities that share common manifestations. This continuum supports the concept of somatic mosaicism. © 1993 Wiley‐Liss, Inc.
Cranial base and face in mandibulofacial dysostosis
Authors: Kreiborg Sven , Dahl Erik
Published: June 2005

Using longitudinal roentgencephalometry, we studied craniofacial growth in two children with mandibulofacial dysostosis. In one child, data were supplemented by three‐dimensional reconstructions of CT scans and stereolithographic models of the craniofacial skeleton. Progressive basilar kyphosis was found in both children, the hypothesized cause being bending of the cranial base at the level of the sphenofrontal suture. Such bending acting in concert with abnormal growth of the mandible led to impairment of the airway. We advocate careful monitoring of craniofacial growth and respiratory function in mandibulofacial dysostosis from birth through adolescence. © 1993 Wiley‐Liss, Inc.
Angel‐shaped phalango‐epiphyseal dysplasia (ASPED): Identification of a new genetic bone marker
Authors: Giedion A. , Prader A. , Fliegel C. , Krasikov N. , Langer L. , Poznanski A.
Published: June 2005

We describe a “new” mild malformation of the phalanx, which we call the “angel‐shaped phalanx” (ASP) because of its resemblance to the little angels used for the decoration of Christmas trees. A particular middle phalangeal type of ASPs is found in a distinct variety of multiple epiphyseal dysplasia with marked retardation of bone age and severe coxarthrosis in adult life, previously reported as “hereditary peripheral dysostosis” [Bach‐man, 1967: Proc R Soc Med 60:21–22; Giedion, 1969: Fortschr Rontgenstr 110:507–524]. However, these authors overlooked the unique configuration of the middle phalanges. We renamed the condition “angel‐shaped phalango‐epiphyseal dysplasia (ASPED)”, which may be transmitted in an autosomal‐dominant manner.

Six new patients are added, bringing the total to nine patients (two families and two isolated patients). ASPs were seen in five of six children. The ASPs grew into inconspicuous brachydactyly after physeal closure (3/3). The most important additional radiological finding is late and dysplastic development of both femoral heads (5/5), leading to Pertheslike and osteoarthritic changes and severe hip pain in the early thirties (2/2 adults, having reached this age). The marked retardation of carpal bone age may lead to unnecessary clinical evaluation for endocrine disorders. Less frequent clinical manifestations of ASPED are hyperextensibility of the interphalangeal joints (7/9) and hypodontia (4/7).

Other types of ASPs are observed in brachyphalangy type C, spondylo‐megepiphyseal‐metaphyseal dysplasia, and other conditions.

The concept of mild bone abnormalities as specific markers for genetic disease, as with cone‐shaped epiphyses and now evident in ASPED, may also be useful for ASPs in general. © 1993 Wiley‐Liss, Inc.
Schimke immuno‐osseous dysplasia: Case report and review
Authors: Ludman Mark D. , Cole David E. C. , Crocker John F. S. , Cohen M. Michael
Published: June 2005

We report on a patient with Schimke immunoosseous dysplasia, an autosomal recessive disorder, and review nine patients from the literature. Manifestations include spondyloepiphyseal dysplasia, lymphopenia, signs of defective cellular immunity, and progressive renal disease. This is the first patient known to have the additional findings of thrombocytopenia and microdontia. © 1993 Wiley‐Liss, Inc.
Historical case of dwarfism: Attempted diagnosis
Authors: Wiedemann Hans‐Rudolf
Published: June 2005

A brief description is given of a male dwarf painted by the Italian artist Geromo Induno in 1852. This portrayal seems not to have been mentioned previously in the medical literature. Several experts were consulted in an attempt to diagnose the underlying skeletal dysplasia. Most opted for pseudoachondroplasia, with the most detailed argument coming from the subject of this Festschrift. © 1993 Wiley‐Liss, Inc.
Another postnatal‐onset obesity syndrome
Authors: Camera Gianni , Marugo Mario , Cohen M. Michael
Published: June 2005

We describe an apparently newly recognized postnatal‐onset obesity syndrome with short stature, mental deficiency, hypogonadism, micropenis, contractures of the fingers, and cleft lip‐palate. Comparison is made with other postnatal‐onset obesity syndromes, particularly Vasquez syndrome and Urban syndrome. The cause of our patient's syndrome is unknown at present. We encourage the reporting of other cases to help clarify whether our patient represents a separate entity. © 1993 Wiley‐Liss, Inc.
Parental origin of chromosome 4p deletion in Wolf‐Hirschhorn syndrome
Authors: Dallapiccola Bruno , Mandich Paola , Bellone Emilia , Selicorni Angelo , Mokin Vahe , Ajmar Franco , Novelli Giuseppe
Published: June 2005

We report on molecular studies in 7 patients with Wolf‐Hirschhorn syndrome (WHC) not showing an obvious chromosome 4p deletion. Analysis of a set of polymorphic probes mapping in the 4p16.3 region showed the absence of paternal haplotypes in 5 cases, and maternal haplotypes in 2. These observations corroborate evidence for preferential paternal origin of the de novo 4p chromosome deletion. The overall results of molecular studies suggest that the preponderance of paternally derived WHC could be due, rather than to imprinting of this region, to an excess of structural rearrangements in the male meiosis, related to differences between the mechanisms of sperm and egg production. © 1993 Wiley‐Liss, Inc.
Mild Brachmann‐de Lange syndrome. Phenotypic and developmental characteristics of mildly affected individuals
Authors: Moeschler John B. , Graham John M.
Published: June 2005

Since 1981, we have identified 3 patients with mild Brachmann‐de Lange syndrome (BDLS) who have had subtle but definite manifestations of the syndrome and mild effects on growth and development.

J.G. (B.D. 12/9/72) was first examined at 20 months. He had rather typical craniofacial findings and hirsutism, limitation of full supination of his arms, and brachyclinodactyly of the 5th fingers. IQ was estimated at 65.

K.H. (B.D. 10/10/83) was first examined by us at age 9 months and was diagnosed as having “mild” BDLS. At age 5, K.H. has demonstrated relatively normal cognitive development (low average–average IQ of 74) with specific learning problems: weakness of visual‐motor skills, delayed expressive language development, and articulation difficulties. At age 7, he was attending a regular 1st grade classroom, with some special education assistance.

M.E.(B.D. 4/19/78) was diagnosed at age 10 years as having “mild” BDLS. His physical changes were more subtle than those of the 2 patients above. At age 10, M.E. was in the regular 4th grade classroom receiving special education support. His IQ was in the borderline‐low‐average range. He had strengths in rote verbal skills, with weaknesses in reading and writing.

These 3 patients demonstrate mild BDLS in which characteristic manifestations of the syndrome, particularly craniofacial anomalies, are present and recognizable, but quite subtle, thus making the clinical diagnosis difficult. In addition, the milder physical phenotype is associated with milder cognitive and behavioral consequences. When comparing patients with mild BDLS to those in our practice (4 others) with typical changes, we find that birth weight, absence of major anomalies, and subtlety of craniofacial abnormalities are predictive of mildly affected patients. © 1993 Wiley‐Liss, Inc.
Variability of the Brachmann‐de Lange Syndrome
Authors: Selicorni A. , Lalatta F. , Livini E. , Briscioli V. , Piguzzi T. , Bagozzi D. Clerici , Mastroiacovo P. , Zampino G. , Gaeta G. , Pugliese A. , Cerutti‐Mainaroli P. , Guala A. , Zelante L. , Stabile M. , Belli S. , Franceschini P. , Gianotti A. , Scarano G.
Published: June 2005

Brachmann‐de Lange syndrome (BDLS) is a relatively common multiple congenital anomaly/mental retardation syndrome, whose cause is unknown. The clinical variability of this condition is well‐known. Recently some reports suggested the possible existence of a mild BDLS phenotype.

We report on 30 patients in whom a diagnosis of BDLS was made or strongly suspected in 12 different Italian hospitals. Based on clinical evaluation we divided them into two groups, classical and mild BDLS cases. We compare the clinical data of these patients and we discuss the problems which arise in trying to define clear criteria of distinction between these two groups. © 1993 Wiley‐Liss, Inc.
Mild mental retardation with classic somatic phenotype in the Brachmann‐de Lange syndrome
Authors: Clericuzio Carol L.
Published: June 2005

Severe Mental retardation is the most handicapping disability for individuals with Brachmann‐de Lange syndrome (BDLS). Reports of higher functioning patients with suspected BDLS have invariably described those with a “mild” BDLS somatic phenotype. Here we report on 2 high‐functioning females, ages 3.7 and 10.6 years, with the classic BDLS somatic phenotype, i.e., all growth parameters at 4–5 standard deviations bellow the mean prenatally and postnatally. These 2 patients serve to extend the spectrum of classic BDLS to include cognitive function in the mild‐to ‐moderate range of mental retardation. © 1993 Wiley‐Liss, Inc.
Brachmann‐de Lange syndrome with normal IQ
Authors: Saal Howard M. , Samango‐Sprouse Carole A. , Rodnan Leslie A. , Rosenbaum Kenneth N. , Custer Deborah A.
Published: June 2005

The Brachmann‐de Lange syndrome is a disorder with a high degree of clinical variability, generally associated with moderate to severe mental retardation. To date, 7 previous cases of Brachmann‐de Lange syndrome with normal intelligence (IQ > 70) have been described. We report the eighth case of Brachmann‐de Lange syndrome with normal intelligence. In reviewing thr literature, consistent clinical menifestations seen in these 8 patients that are of prognostic value are the absence of significant limb anomalies and birth weight > 2,500 g. © 1993 Wiley‐Liss, Inc.
Developmental data on individuals with the Brachmann‐de Lange syndrome
Authors: Kline Antonie D. , Stanley Christian , Belevich Jacqueline , Brodsky Karen , Barr Marie , Jackson Laird G.
Published: June 2005

One hundred twenty‐two patients with clinically confirmed Brachmann‐de Lenge syndrome (BDLS) were evaluated developmentally. Recruitment was made from our genetics department and through meetings of the Cornelia de Lange Syndrome Foundation parent support group. Developmental information was obtained from records of physicians, schools and developmental centers, or from parents on each of the 122 individuals, allowing division in to four groups for study: group 1 (n = 48) underwent formal developmental assessments, which generated intelligence or developmental quotients, and had a completed parental questionnaire with specific developmental questions regarding ages of skills mastered; group II (n = 23) had additional developmental records available without formal testing, as well as the questionnaire; group III (n = 22) had a only a completed questionnaire; and group IV (n = 29) had formal developmental testing or other developmental records but no available questionnaire. These data were analyzed in order to be able to predict attainable psychomotor development. Average scores on formal testing were found to be in the mild to moderate level of mental retardation, ranging from below 30 to 85, with an average intelligence quotient of 53, higher than previously reported. Visual‐spatial memory and perceptual organization skills were found to be strengths. Younger individuals born before 1980 demonstrated higher scores on testing. Early intervention appears to play a major role in the level of developmental achievement. © 1993 Wiley‐Liss, Inc.
DiGeorge anomaly with renal agenesis in infants of mothers with diabetes
Authors: Wilson Thomas A. , Blethen Sandra L. , Vallone Ambrose , Alenick D. Scott , Nolan Patricia , Katz Arnold , Amorillo Thomas P. , Goldmuntz Elizabeth , Emanuel Beverly S. , Driscoll Deborah A.
Published: June 2005

We report on 2 infants with the DiGeorge anomaly born to diabetic mothers treated with insulin. Both infants had unilateral renal agenesis. One of the mothers has manifestations suggestive of velo‐cardio‐facial syndrome (VCFS). Cytogenetic studies on both patients and the mother with apparent VCFS were normal. Molecular studies utilizing probes from the DiGeorge critical region did not demonstrate a 22q11 microdeletion in either patient or the mother with apparent VCFS. We conclude that maternal diabetes is a pathogenetic factor in the DiGeorge anomaly, and infants of diabetic mothers who have this anomaly should also be screened for renal agenesis. © 1993 Wiley‐Liss, Inc.
Roberts syndrome: A review of 100 cases and a new rating system for severity
Authors: Van Den Berg David J. , Francke Uta
Published: June 2005

Roberts syndrome (RS) is a rare genetic disorder characterized by pre‐ and postnatal growth retardation, limb defects, and craniofacial anomalies. Affected persons have varying degrees of malformations involving symmetric reduction in the number of digits, and length or presence of bones in the arms and legs. Craniofacial malformations involve hypertelorism, hypoplastic nasal alae, and a high incidence of cleft lip and palate. Familial and sporadic cases have been reported consistent with an autosomal recessive mode of inheritance. Mitotic cells from many individuals with RS display a characteristic cytogenetic phenomenon consisting of repulsion of heterochromatic regions near centromeres, particularly of chromosomes 1, 9, 16, and splaying of the short arms of the acrocentrics and of the distal Yq. Mitosis in RS cells is abnormal in metaphase duration and anaphase progression. Specifically, anaphase figures show a higher degree of chromosomes that are outlying, lagging, or prematurely advancing toward the poles compared to normal controls. RS cells have abnormal nuclear morphology and also show a higher frequency of micronucleation than normal cells, presumably as a result of the abnormal mitotic events during anaphase. Therefore, RS has been interpreted as a human mitotic mutation syndrome which leads to secondary developmental defects. This report reviews 100 cases of RS, summarizes the phenotypic, genetic, cytogenetic, and cell biology findings in Roberts syndrome, and introduces the RS Rating for quantitating severity. © 1993 Wiley‐Liss, Inc.
Malformations and deformations in abdominal pregnancy
Authors: Stevens Cathy A.
Published: June 2005

Abdominal gestation is a relatively uncommon complication of pregnancy. Previous reports describe a high incidence of fetal deformations and mortality as well as maternal mortality. A case of twin abdominal gestation is presented and the literature concerning abdominal pregnancy since 1809 is reviewed. The survival rate of liveborn infants of 30 or more weeks gestation was 63%. The maternal mortality rate since 1809 was 18.2%, but this has decreased to 4.5% during the last 20 years. The combined rate of malformations and deformations in the infants was 21.4%. The most common deformations observed were facial and/or cranial asymmetry and various joint abnormalities. Among the most common malformations were limb deficiency and central nervous system malformations. Proposed mechanisms of compression and vascular disruption are discussed. © 1993 Wiley‐Liss, Inc.
Genetic etiology of nuclear cataract: Evidence for a major gene
Authors: Heiba Ibrahim M. , Elston Robert C. , Klein Barbara E. K. , Kein Ronald
Published: June 2005

Sibling correlations and segregation analysis were used to examine the familial distribution of age‐sex‐adgusted measures of nuclear sclerosis in 1,247 individuals from 564 sibships in the Beaver Dam Eye Study. There are highly significant sibling correlations for all sibs, and separately for sister‐sister, sister‐brother, and brother‐brother pairs. Two transformed normal distributions give the best fit to the data. The hypothesis of mendelian transmission of a major effect cannot be rejected, but the hypothesis of a random environmental major effrect is rejectd. The parameters of the τABfree model showed close similarity to the values expected under a mendelian hypothesis. Our results suggest that a single major gene can account for 35% of the total variability of age‐sex‐adjusted measures of nuclear sclerosis. © 1993 Wiley‐Liss, Inc.
Familial remitting chorea, nystagmus, and cataracts
Authors: Wheeler Patricia G. , Dobyns William B. , Plager David A. , Ellis Forrest D.
Published: June 2005

We report on 2 brothers with chorea and monocular horizontal nystagmus beginning in early infancy, both of which remit during the first decade of life, and peripheral cataracts. While this condition shares manifestations with benign hereditary chorea and several other familial movement disrders, the slowly remitting course of the chorea combined with the visual abnormalities appears to be unuque. © 1993 Wiley‐Liss, Inc.
Further characterization of 19 cases of rea(21q21q) and delineation as isochromosomes or robertsonian translocations in down syndrome
Authors: Shaffer Lisa G. , McCaskill Christopher , Haller Vickie , Brown Judith A. , Jackson‐Cook Colleen K.
Published: June 2005

We have used 9 conventional RFLPs and 6 dinucleotide repeat polymorphisms on chromosome 21q to demonstrate that 17 of 19 cases of rea(21q21q) were consistent with isochromosomes i(21q) with the remaining 2 being true Robertsonian translocations. Eight of the 17 isochromosomes were of maternal origin and 9 cases were paternally derived. The 2 Robertsonian translocations were both maternally derived. Of the 17 isochromosomes, 7 were dicentric Wc(21q)I and 10 were monocentric M21q)l. Both rob(21q21q) were monocentric. Our findings agree with those made in 17 previously published cases of rea(21q21q). The parental origins of the i(21q) were equally divided between maternal (n = 17) and paternal (n = 15) origins. All 4 true rob(21q21q) reported to date are of maternal origin. Collectively, it appears that most homologous rearrangements of chromosome 21 are isochromosomes and only a small proportion are consistent with true Robertsonian translocations. © 1993 Wiley‐Liss, Inc.
C to T nucleotide substitution in codon 713 of amyloid precursor protein gene not found in 86 unrelated schizophrenics from multiplex families
Authors: Coon Hilary , Hoff Mark , Holik John , Delisi Lynn E. , Crowe Timothy , Freedman Robert , Shields Gail , Boccio Angela M. , Lerman Melissa , Gershon Elliot S. , Gejman Pablo V. , Leppert Mark , Byerley William
Published: June 2005

Jones et al. Nature Genet 1:306–309, [1992] recently detected a C to T nucleotide transition (codon 713) in a highly conserved region of the beta‐amyloid precursor gene in a single case of schizophrenia. Although the sequence variant may be a natural polymorphism, it is crucial to determine whether the mutation might be present in a small subset of schizophrenics. We isolated DNA from 86 unrelated chronic schizophrenics who had a first degree relative with chronic schizophrenia or chronic schizoaffective disorder. After PCR amplification of exon 17, we were unable to detect the presence of the codon 713 variant in these schizophrenic cases, as well as in 156 controls. Unless additional cases are found with the codon 713 mutation, it is unlikely that the sequence variant is pathogenic for schizophrenia. © 1993 Wiley‐Liss, Inc.
DSM‐III‐R personality disorders in parents of schizophrenic patients
Authors: Dorfman Arlene , Shields Gail , Delisi Lynn E.
Published: June 2005

This study examines the frequency of DSM‐III‐R personality disorders in parents of 58 patients who were admitted consecutively to a New York State psychiatric hospital with a first admission for a schizophrenia‐like psychosis. For comparison, a control group of 65 families were randomly recruited who were in the same age group and denied any psychiatric history in their immediate families. Significantly more parents of the patients had a diagnosed personality disorder than controls. These were classificed as schizoid, schizotypal, histrionic, and sadistic types by DSM‐III‐R criteria. While paranoid personality disorder was frequent, it was equally distributed among both groups of parents. These data suggest that the genetic boundaries to a “schizophrenia spectrum” disorder may extend further than previously thought and particularly the specific characteristics that are common to a wide variety of these disorders need to be examined in further analyses. © 1993 Wiley‐Liss, Inc.
Review of the putative association of dopamine D2 receptor and alcoholism: A meta‐analysis
Authors: Pato Carlos N. , Macciardi Fabio , Pato Michele T. , Verga Massimiliano , Kennedy James L.
Published: June 2005

Eight recent studies have focused on the putative association of the dopamine D2 receptor (DRD2) gene and alcoholism. In this report, these studies are reviewed and the data and findings are examined in a meta‐analysis. Four reports find a statistically significant increased risk for alcoholism in subjects carrying the A1 allele and 4 failed to observe a significant increase in risk. Overall, our metaanalysis of the results from all 8 studies supported a statistically significant association between the A1 allele of DRD2 and alcoholism, with an apparent increase in relative risk associated with increased severity of alcoholism. These results must be interpreted cautiously because the A1 allele of DRD2 varies significantly in frequency from one population to another. This variability in the population frequency of the A1 allele could result in an apparent association resulting from unrelated population differences. These findings support the need for carefully designed studies that minimize the ethnic heterogeneity of the subject and control populations. © 1993 Wiley‐Liss, Inc.
On attitudes and appreciation 6 months after predictive DNA testing for huntington disease in the Dutch program
Authors: Tibben Aad , Frets Petra G. , van de Kamp Jacques J. P. , Niermeijer Martinus F. , der Vlis Maria Vegtervan , Roos Raymund A. C. , Rooymans Harry G. M. , van Ommen Gert‐Jan B. , Verhage Frans
Published: June 2005

We have studied the 6‐month follow‐up attitudes of 63 individuals, after predictive testing for Huntington disease (HD). Reducing uncertainty (81%) and family planning (60%) were the major reasons for taking the test. Twenty‐four individuals were diagnosed as having an increased risk (± 98%), and 39 a decreased risk (± 2%).

Among those with an increased risk, denial or minimization of the ultimate impact of the increased risk result was observed. Most of them (84%) rated their current life situation, at the very least, as being good. Twenty‐one percent of individuals with an increased risk who originally planned to have a family, decided to refrain from having children. Sixty percent of those with increased risk who still wished to have children, would choose to have prenatal testing. In most individuals with increased risk, the test result did not increase the previously expected control over their own future.

Half of the partners of persons with increased risk acknowledged the burden of the future disease. Half had no one in whom they could confide. They showed loyalty to the denial and avoidance reactions of their spouses.

Half of the individuals with decreased risk denied the impact of the result, as reflected by absence of relief, and emotional numbness. A third of persons with decreased risk experienced involvement with problems of affected relatives.

We found that 20% of all participants were discontented with the support given by their general practitioner, who is normally regarded as being the most significant professional for aftercare. Our findings suggest that the perpetuation of psychological defenses, which may temporarily be adequate, may ultimately prevent an individual from taking advantage of being informed. These questions should be further addressed in long‐term follow‐up studies. © 1993 Wiley‐Liss, Inc.
Association of monoamine oxidase (MAO) activity with alcoholism and alcoholic subtypes
Authors: Devor Eric J. , Cloninger C. Robert , Hoffman Paula L. , Tabakoff Boris
Published: June 2005

A familial/genetic study of platelet monoamine oxidase (MAO) activity in alcoholics was carried out. MAO activities were determined using phenylethylamine (PEA) as substrate at Km concentration (1.2 μM) and at saturating concentration (12.0 μM). Complex segregation analysis of familial data indicated a single major gene mode of transmission of activity at both substrate concentrations. In addition, the present sample size (13 families, 108 members) proved sufficient to allow correlation analysis of enzyme activity with affection status and clinical subtypes of affecteds. MAO activity was significantly correlated with alcoholism at both Km and saturating substrate concentrations and a significant correlation between low MAO activity and Cloninger Type II alcoholism was seen at Km substrate concentration. These results confirm a hierachical cosegregation of platelet MAO activity and alcoholism suggesting that MAO activity warrants continued status as a marker in alcoholism. © 1993 Wiley‐Liss, Inc.
Rett syndrome associated with tuberous sclerosis in a male and in a female: Evidence for arrested motor and mental development
Authors: Philippart Michel
Published: June 2005

Two sporadic cases of tuberous sclerosis presented with flexion spasms in a male and early intractable seizures evolving into a Lennox–Gastaut syndrome in a female. Early hypotonia and lack of substantial motor development are key features of the Rett syndrome, more easily overlooked than hand‐wringing. Clumsy self‐feeding and immature ambulation were the highest achievements in the second case now aged 36 years. Immaturity rather than degeneration, dementia, or assumed tissue destruction, is the capital feature of many disorders of early brain development leading to profound motor as well as mental retardation. Studying unusual clinical combinations is more likely to shed light on the underlying etiology than focusing on procrustean syndrome definitions. © 1993 Wiley‐Liss, Inc.
Genetic disorders that masquerade as multiple sclerosis
Authors: Natowicz Marvin R. , Bejjani Bassem
Published: June 2005

There are many genetic disorders that have signs and symptoms suggestive of multiple sclerosis and that may easily be overlooked in the evaluation of both adult and pediatric multiple sclerosis patients. The recognition of a genetic disorder as the cause of a patient's “multiple sclerosis” phenotype has important implications not only for the patient, but often also for others in the patient's family who may be at risk for the same disease. We present here a review of single gene disorders that can masquerade as multiple sclerosis. For each disorder, the major clinical and biochemical characteristics are discussed, together with the appropriate testing to screen for and confirm the diagnosis. In addition, guidelines are presented for when to suspect an underlying genetic condition in a patient with a diagnosis of definite or probable multiple sclerosis. The great variety of genetic disorders that can masquerade as multiple sclerosis and the many implications of a genetic diagnosis underscore the importance of recognizing genocopies of multiple sclerosis. © 1994 Wiley‐Liss, Inc.
Walker‐Warburg syndrome: Report of three affected sibs
Authors: Rodgers Benjamin L. , Vanner Lauren V. , Pai G. S. , Sens Mary Anne
Published: June 2005

Walker‐Warburg syndrome (WWS) is a lethal, autosomal recessive disorder characterized by Type II lissencephaly, retinal malformation, cerebellar malformation, and congenital muscular dystrophy. We report on 3 sibs with WWS born to a consanguineous couple. The fetal hydrocephalus associated with this syndrome, while not consistent or necessary for diagnosis, is the key manifestation for its prenatal detection. These sibs illustrate the importance of a careful search for associated malformation(s) in a fetus or newborn infant with hydrocephalus and the potential pitfalls of accurate genetic risk estimation in families of such propositi. © 1994 Wiley‐Liss, Inc.
Prenatal diagnosis of Smith–Lemli–Opitz syndrome, type II
Authors: Johnson Judith A. , Aughton David J. , Comstock Christine H. , von Oeyen Paul T. , Higgins James V. , Schulz Rex
Published: June 2005

Smith–Lemli–Opitz syndrome, type II (SLOS‐II) is a severe autosomal recessive disorder characterized by a distinctive face, unusual cleft palate, postaxial polydactyly, congenital heart defects, renal anomalies, and male pseudohermaphroditism. We present the first report of prenatal diagnosis of SLOS‐II, as well as an additional report of prenatal detection of multiple anomalies, in which a positive diagnosis of SLOS II was made postanatally. In neither case was the pregnancy known prospectively to be at risk for SLOS‐II. In the former case, targeted sonographic examination at 31 weeks of gestation showed intrauterine growth retardation, atrioventricular septal defect, mesomelic shortening of the arms, small kidneys, overlapping fingers, and female external genitalia; a 46,XY chromosome constitution had been ascertained previously. A provisional diagnosis of SLOS‐II was made prenatally. In the latter case, targeted sonographic examination at 18 weeks of gestation showed severe oligohydramnios, atrioventricular septal defect, and Dandy–Walker malformation. The kidneys and bladder were not visualized. The chromosome constitution was 46,XX. The diagnosis of SLOS‐II was made postnatally. In both cases, additional findings compatible with SLOS‐II were noted postnatally. Prenatal detection of congenital heart defects and renal abnormalities, in combination with certain additional findings (most notably, female external genitalia in the presence of a 46,XY karyotype, polydactyly, disproportionately short limbs, or intrauterine growth retardation) and a normal karyotype, suggests the diagnosis of SLOS‐II, and warrants further investigation. © 1994 Wiley‐Liss, Inc.
Juvenile variant of Schimke immunoosseous dysplasia
Authors: Hashimoto Kazuhiro , Takeuchi Ariko , Ieshima Atsushi , Takada Mitsuyoshi , Kasagi Masaaki
Published: June 2005

We report on a 16‐year‐old girl with spondyloepiphyseal dysplasia, nephrotic syndrome, lymphopenia, and signs of defective cellular immunity. The manifestations are very similar to those reported by Spranger et al. [1991: J Pediatr 119:64–72] as Schimke immunoosseous dysplasia, except for age of onset. In Schimke immunoosseous dysplasia, growth retardations as an initial symptom is noted in early childhood and about 1 year after onset of progressive proteinuria. In our case the skeletal abnormality was noted at age 10 years as dislocation of the hip joints and the diagnosis of nephrotic syndrome was made at age 16 years. The findings strongly suggest that our patient has a juvenile variant of Schimke immunoosseous dysplasia. © 1994 Wiley‐Liss, Inc.
Restoration of half the normal dystrophin sequence in a double‐deletion Duchenne muscular dystrophy family
Authors: Hoop R. C. , Russo L. S. , Riconda D. L. , Schwartz L. S. , Hoffman E. P.
Published: June 2005

Two male cousins with Duchenne musoular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions—one in the 5′, proximal deletional hotspot region, and the other in the 3′, more distal deletional hotspot region. The second propositus showed only the 5′ deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, we show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier's dystrophin genes, giving rise to a son with a partially “repaired” gene retaining only the 5′ deletion. © 1994 Wiley‐Liss, Inc.
Bilateral coats retinopathy associated with aplastic anaemia and mild dyskeratotic signs
Authors: Kajtár Pál , Méhes Károly
Published: June 2005

A 2‐year‐old girl presented with thrombocytopenic purpura. Clinical examination and follow‐up documented severe bone marrow hypoplasia associated with bilateral progressive Coasts retinopathy, nail dystrophy, fine hair, and apparent chromosome instability. The syndrome is regarded as a variant of the Révész syndrome sharing some findings of dyskeratosis congenita. © 1994 Wiley‐Liss, Inc.
Unstable pre‐mutation may explain mosaic disease expression of incontinentia pigmenti in males
Authors: Traupe Heiko , Vehring Karl‐Heinz
Published: June 2005

Mosiac skin lesions following the lines of Blaschko are found in boys affected by incontinentia pigmenti (IP). For an X‐linked gene defect, this is rather surprising. To explain the mosaic disease expression of IP in males, we propose that the disease is caused by an unstable pre‐mutation, which normally remains silent in males during early embryogenesis. Occasionally “silencing” is incomplete and gives rise to clinical manifest IP reflecting a mosaic state of alleles with the full and the pre‐mutation in the same patient. This model can account for mother‐to‐son transmission of IP and for disparate phenotypes in monozygotic female twins. © 1994 Wiley‐Liss, Inc.
Branchio‐oculo‐facial syndrome: Broadening the spectrum
Authors: McCool Michelle , Weaver David D.
Published: June 2005

We present 3 individuals, a mother, her son, and an unrelated child, with a number of manifestations reported in the branchio‐oculo‐facial syndrome (BOFS). The former 2 individuals lacked the ocular and branchial abnormalities normally encountered in this syndrome. However, unilateral renal agenesis was present in the first child, a defect infrequently found in the BOF syndrome. Both the mother and her son also had bilateral supra‐auricular sinuses. These defects may represent persistence of the otic vesicle sinus tract. The second child has a mild expression of this condition, among the mildest reported in the literature. The BOFS appears to represent a spectrum involving the development of the optic vesicles, branchial arches, eyes, face, lips, and kidneys. The variations seen in this disorder and the overlap between this condition and the branchio‐oto‐renal syndrome may represent different mutations within a single gene or may be a contiguous gene deletion syndrome. © 1994 Wiley‐Liss, Inc.
Further delineation of pseudotrisomy 13 syndrome: A case without polydactyly
Authors: Ramos‐Arroyo M. A. , de Miguel C. , Valiente A. , Moreno‐Laguna S.
Published: June 2005

We report on a baby with holoprosencephaly, median cleft lip, cardiac and genital anomalies, normal upper limbs, and a 46,XX karyotype. We also reviewed 22 karyotypically normal cases whose clinical features resembled trisomy 13 syndrome and compared them with the case we present. The problem of variable expression of the pseudotrisomy 13 syndrome versus genetic heterogeneity is illustrated. © 1994 Wiley‐Liss, Inc.