bluuebunny/crossref_metadata_2025 huggingface dataset:
Autosomal dominant tetramelic postaxial oligodactyly
Authors: Wulfsberg Eric A. , Mirkinson Laura J. , Meister Steven J.
Published: June 2005

Postaxial limb deficiencies are most frequently unilateral and sporadic with deficiencies of the ulnar ray about one‐third as common as those affecting the radial ray. Postaxial deficiency occurs in a number of genetic and sporadic syndromes, but isolated inherited tetramelic, postaxial oligodactyly has to our knowledge not been described. We report an affected mother and her 3 affected children from a 4‐generation family with apparent autosomal dominant, non‐syndromic, tetramelic, postaxial oligodactyly. The affected individuals manifest a very uniform pattern of postaxial deficiency ranging from complete absence of the 5th metacarpals, metatarsals, and phalanges to complete absence of the 5th metacarpals and metatarsals, but with some residual distal 5th phalanges.

Limb buds may be considered a single developmental field with development proceeding rostral to caudal. Digit formation is apparently controlled by the zone of polarizing activity which releases a diffusible morphogen specifying positional information along the anterior/posterior axis. Recent investigations using chick and mouse embryo models suggest that 5′ members of the Hox‐4 gene cluster are responsible for interpreting this positional information to effect digit formation. The present family may represent a defect in Hox‐4 gene patterning of hand and foot formation, an abnormality in morphogen gradient formation or alternately an inability of the most ulnar rays to respond to morphogen (receptor defect). © 1993 Wiley‐Liss, Inc.
Proliferation and collagen biosynthesis of osteoblasts and chondrocytes in short rib syndrome type beemer
Authors: Brenner Rolf E. , Nerlich Andreas , Kirchner Frank , Mörike Martin , Terinde Rainer , Teller Walter M.
Published: June 2005

We report on a case of lethal short‐limbed skeletal dysplasia with extremely short ribs, median cleft upper lip and palate, malrotation of intestine, lung hypoplasia with bilateral segmentation defect, atrial septum defect, union of distal urethra and vagina, and complex brain malformations. Based on radiological criteria and the pattern of associated abnormalities a short rib syndrome without polydactyly (Type Beemer) was diaguosed. Morphologically, the growth plate showed a reduced proliferation zone and an enlarged zone of hypertrophic cartilage. In addition, islands of persistent hypertrophic cartilage were present even in the metaphysis. In monolayer cell cultures supplemented with 10% fetal calf serum proliferation was normal in articular chondrocytes, reduced in costal chondrocytes, and elevated in osteoblasts from the patient. Clonal growth of costal and articular chondrocyted in methylcellulose could be stimulated normally by insulin‐like growth factor‐I (IGF‐I), IGF‐II, and human growth hormone (hGH). However, the response to transforming growth factor β1 (TGF‐β1) was markedly elevated in articular chondrocytes of the patient compard to those of 3 fetal controls. Quantitative collagen synthesis in both osteoblasts and chondrocytes from the patient did not differ significantly from that of controls. Osteoblasts synthesized predominantly collagen I and minor amounts of collagen III, chondrocytes synthesized primarily collagen II. All collagen chains including CNBr‐peptides of collagen II showed normal migration in PAA gel electrophoresis.
Oculocerebral hypopigmentation syndrome associated with Bartter syndrome
Authors: White C. P. , Waldron M. , Jan J. E. , Carter J. E.
Published: June 2005

We describe a 20‐year‐old man with tyrosinase‐negative oculocutaneous albinism, mental retardation, epilepsy, sensorineural deafness, ataxia, and Bartter syndrome. When combined, these neurocutaneous and renal findings form a previously unreported combination.

The neurological and cutaneous manifestations of this case are distinctly different from those of the syndrome first reported by Cross et al. [1967]. The literature is reviewed and an attempt is made at classifying the oculocerebral hypopigmentation syndromes. © 1993 Wiley‐Liss, Inc.
Clinical and molecular analyses of deletion 3p25‐pter syndrome
Authors: Mowrey Philip N. , Chorney Michael J. , Venditti Charles P. , Latif Farida , Modi William S. , Lerman Michael I. , Zbar Berton , Robins David B. , Rogan Peter K. , Ladda Roger L.
Published: June 2005

Hemizygous deletion of 3p25‐pter is associated with a phenotype of profound growth failure, microcephaly, characteristic facial changes, and mental retardation. Since the severity may be quite variable, we have studied 3 cases of del 3p25‐pter to define the clinical manifestations and the critical chromosome region for phenotypic expression. The patient we now report died at age 6 months and provided an opportunity for a detailed necropsy analysis for only the second time in a del(3p) patient. He had marked hypoplasia of all organs, hypomyelination of white matter, and multiple renal cortical microcysts. Ordered genomic markers from the distal regions of chromosome 3p aided in determining the parent of origin of each deletion and in defining the boundaries of the deleted chromosomal segments. The deleted markers distal to the RAF1 oncogene in 2 of the 3 patients were consistently hemizygous. One patient had an interstitial deletion based on evidence of diploid inheritance of one of the most distal loci (D3S17). Available genetic linkage maps suggest that the deletion spans at least 19 centimorgans (cM). © 1993 Wiley‐Liss, Inc.
Case of ring chromosome 7: The first report of neuropathological findings
Authors: Tsukamoto Hiroko , Sakai Norio , Taniike Masako , Nakatsukasa Mitsuto , Yoshiwara Wataru , Sakamoto Hiromi , Fujimura Harutoshi , Inui Koji , Okada Shintaro
Published: June 2005

We report on a boy with ring chromosome 7 who had severe mental retardation, growth failure, microcephaly, cleft lip and palate, café‐au‐lait sports, nevus flammeus, and genital abnormalities, and died of pneumonia at age 20 months. On autopsy he had fusion of the anterior cerebral hemispheres, accompanied by agenesis of olfactory bulbs and tracts, closely resembling those found in semi‐lobar holoprosencephaly. In addition, heterotopic Purkinje cell cluster in the cerebellar white matter, absence of pigmentation within the brainstem pigmented neurons, and severe hypomyelination in the whole brain were noted.

The patient may represent the most severe manifestation of ring chromosome 7, and this is the first detailed neuropathological report on this subject. © 1993 Wiley‐Liss, Inc.
Prenatal in situ hybridization test for deleted steroid sulfatase gene
Authors: Lebo Roger V. , Lynch Eric D. , Golbus Mitchell S. , Flandermeyer Robert R. , Yen Pauline H. , Shapiro Larry J.
Published: June 2005

X‐linked ichthyosis results from steroid sulfatase (STS) deficiency; 90% of affected patients have a complete deletion of the entire 146 kb STS gene on the distal X chromosome short arm (Xp22.3). In these families prenatal diagnosis and carrier testing can be completed in 2 days by hybridizing simultaneously 2 different cosmid probes labeled with fluorescein or Texas red and counterstaining interphase nuclear DNA with DAPI. An STS gene probe labeled with Texas red hybridizes specially to the steroid sulfatase gene on the X chromosome. A second flanking probe labeled with fluorescein hybridizes to both the normal Y chromosome and normal and STS deleted X chromosomes. In this fashion the interphase nuclei of normal males, affected males, normal females, and carrier females can be distinguished unambiguously. Because normal males and carrier females each show two yellow‐green fluorescein spots and one Texas red STS spot, use of this test prenatally requires determining fetal sex independently with repetitive X and Y chromosome specific probes. This procedure can be used with lymphocytes, direct and cultured chorionic villus cells, direct and cultured amniocytes, and fibroblasts. Similar methods are anticipated to be useful for rapid diagnostic assessment of other aneuploid gene disorders. © 1993 Wiley‐Liss, Inc.
Mandibulofacial dysostosis: Report on two Brazilian families suggesting autosomal recessive inheritance
Authors: Richieri‐Costa A. , Bortolozo M. A. , Lauris J. R. P. , Lauris R. C. M. C. , Guion‐Almeida M. L. , Marques D. , Moreti D.
Published: June 2005

We report on mandibulofacial dysostosis in 2 brothers born to normal nonconsanguineous parents, and a girl (F = 1/16) born to normal consanguineous parents. Normal clinical, skeletal, audiologic, and cephalometric studies in the parents, as well as the absense of limp anomalies in these children, exclude the autosomal recessive (Nager and Genée‐Widemann) mandibulofacial dysostoses. The data of the present patients associated with the few additional reports on mandibulofacial dysostosis recurring in sibs, suggest the possibility of an autosomal recessive Treacher Collins‐like mandibulofacial dysotosis. © 1993 Wiley‐Liss, Inc.
Uniparental disomy revisited: The first twelve years
Authors: Engel Eric
Published: June 2005

Uniparental disomy (UPD), the exceptional derivation of a pair of the offspring chromosomes from one parent only, may be compatible with normal or abnormal development and can result from gamete complementation, chromosome loss in trisomy, or duplication in monosomy, (with or without residual mosaicism) and somatic recombination. In isodisomy, the uniparental pair is a duplicate of a same chromosome DNA template and causes and increased risk or recessive disorder by reduction to homozygosity. In heterodisomy, the pair remains heterozygous, made up of 2 non‐recombinant homologous segments. But both iso‐ and heterodisomy may also cause disruption of the genomic imprints needed for differential expression of some maternal and paternal genes crucial to growth and development. Pure UPD preserves euploidy and, when harmful, is best regarded as a genomic qualitative imbalance by symmetrical excess and loss of parental homologous contribution affecting zygosity and imprint content. Instances of UPD reported till the spring 1992 are reviewed and their deleterious effects are described as they carried out lethality or morbidity by altering imprinting processes, mimicking deletions, generating recessive disorders, or prompting malignant cellular growth. © 1993 Wiley‐Liss, Inc.
Acalvaria: A unique congenital anomaly
Authors: Harris Cheryl P. , Townsend Jeannette J. , Carey John C.
Published: June 2005

Acalvaria is a rare malformation usually regarded as a postneurulation defect. It consists of absense of the calvarial bones, dura mater and associated muscles in the presence of a normal skull base and normal facial bones. The condition is frequenctly confused by prenatal ultrasonography with anencephaly or an encephalocele. Whereas the cerebral hemispheres are absent in anencephaly, the cranial contents in acalvaria are generally complete, though some neuropathological abnormality is often present. The presumed pathogenesis of acalvaria is faulty migration of the membranous neurocranium with normal placement of the embryonic ectoderm, resulting in absence of the calvaria but an intact layer of skin over the brain parenchyma. We describe 2 cases of acalvaria, one misdiagnosed ultrasonographically as an occipital encephalocele prenatally. The brain in one fetus demonstrated semilobar holoprosencephaly and micropolygyria, but in the other, was structurally and histologically normal with the exception of hydrocephalus. © 1993 Wiley‐Liss, Inc.
No evidence for linkage to the type 1 or type 2 neurofibromatosis loci in Noonan syndrome families
Authors: Flintoff Wayne F. , Bahuau Michel , Lyonnet Stanislas , Gilgenkrantz Simone , Lacombe Didier , Marçon François , Levilliers Jacqueline , Kachaner Jean , Munnich Arnold , Merrer Martine Le
Published: June 2005

A linkage analysis has been performed on 6 two‐generation families with classical Noonan syndrome to determine whether the shydrome is linked to neurofibromatosis type 1 on chromosome 17q or to neurofibromatosis type 2 on chromosome 22q. A significantly negative location score was obtained between 10cM centromeric to and 15 cM telomeric from the neurofibromatosis type 1 locus. A significantly negative lod score was obtained with a marker mapping within the region where neurofibromatosis type 2 is thought to be located. These data indicate that Noonan syndrome is not tightly linked to either neurofibromatosis type 1 or type 2. © 1993 Wiley‐Liss, Inc.
Historical essay: Of monsters and prodigies: The interpretation of birth defects in the sixteenth century
Authors: Walton Michael T. , Fineman Robert M. , Walton Phyllis J.
Published: June 2005

In the sixteenth century, a time of religious and social upheaval, naturalistic theories of generation were joined to ideas that monstrous births were divine signs. In this paper, we explore how medicine and theology were combined to explain the almost cataclysmic religious, social and political events of the century. © 1993 Wiley‐Liss, Inc.
Congenital muscular dystrophy with neurological abnormalities: Association with Hirschsprung disease
Authors: Mandel Hanna , Brik Riva , Ludatscher Ruth , Braun Jacob , Berant Moshe
Published: June 2005

We report on a baby girl with congenital muscular dystrophy (CMD) with neurological abnormalities (“CMD Plus” condition), who also had Hirschsprung disease. This association may indicate a category of congenital muscular dystrophy with involvement of the visceral nervous system. We propose that Hirschsprung disease be added to the list of anomalies pertaining to the “CMD Plus” array, and that CMD should be considered when Hirschsprung disease occurs with central nervous system anomalies. © 1993 Wiley‐Liss, Inc.
Congenital pulmonary lymphangiectasis with chylothorax: A heterogeneous lymphatic vessel abnormality
Authors: Moerman Philippe , Vandenberghe Kamiel , Devlieger Hugo , Van Hole Chris , Fryns Jean‐Pierre , Lauweryns Joseph M.
Published: June 2005

We report on 7 perinatal autopsy cases of primary congenital pulmonary lymphangiectasis (CPL) with bilateral chylothorax. This study demonstrates that primary CPL is often complicated by chylous pleural effusions with ensuing pulmonary hypoplasia. Conversely, CPL appears to be a constant pathological finding in spontaneous congenital chylothorax. These observations indicate a common pathogenesis for both disorders. The basic defects is not an intrinsic lung abnormality, but a developmental error of the lymphatic system resulting in a pulmonary lymphatic obstruction sequence.

The cause of CPL is heterogeneous. Apparently, most cases are sporadic occurrences. We report the second instance of CPL in sibs. This indicates that some cases are genetically determined with autosomal recessive inheritance. CPL may also be part of a multiple congenital anomalies (MCA) syndrome such as Noonan, Ullrich‐Turner, and Down syndrome. © 1993 Wiley‐Liss, Inc.
Severe axial anomalies in the oculo‐auriculo‐vertebral (Goldenhar) complex
Authors: Rodríguez José Ignacio , Palacios José , Lapunzina Pablo
Published: June 2005

We have studied 4 infants with oculo‐auriculovertebral (OAV) complex or Goldenhar “syndrome” who also had severe axial anomalies, including multiple vertebral segmentation errors affecting the thoracic and the lumbar spine. One of them presented a previously unreported pattern of vertebral and rib anomalies similar to spondylocostal dysostosis. Three patients had twins, and all 4 patients had other associated non‐skeletal malformations which affected the midline, i.e., cleft lip and palate, esophageal atresia with tracheoesophageal fistula, and ventricular septal defect.

The broad extent of the axial anomalies, the association with midline defects and twinning, and the combination in the same patient of two distinct conditions support the concept that OAV complex is a polytopic developmental field defect arising during blastogenesis. © 1993 Wiley‐Liss, Inc.
Jancar syndrome: Mental retardation, spasticity, and distal transverse limbs defects
Authors: Zlotogora Joël , Glick Benjamin
Published: June 2005

We report on a child with mental retardation, spasticity, and distal transverse defects of the limbs born to healthy parents related as first cousin. This is the third child reported to be affected with the syndrome described by Jancar. We confirm the existence of the syndrome as a separate entity and raise possibility that it may be inherited as an autosomal recessive trait. © 1993 Wiley‐Liss, Inc.
Norman‐Roberts syndrome: Clinical and molecular studies
Authors: Iannetti Paola , Schwartz Charles E. , Dietz‐Band Jeanne , Light Elizabeth , Timmerman Julie , Chessa Luciana
Published: June 2005

We report on a 7‐year‐old boy with microcephaly, bitemporal hollowig, low sloping forehead, slightly prominent occiput, widely set eyes, broad and prominent nasal bridge, and severe postnatal growth deficiency. Hypertonia, hyperreflexia, seizures, and profound mental retardation were also present. Brain MRI documented partial agyric cortex with patchy pachygyria, colpocephaly, and hypoplasia of corpus callosum and brain stem, which is consistent with the diagnosis of lissencephaly type I grade 2. On the basis of his phenotypic appearance the patient is considered to have the Norman‐Roberts syndrome. Molecular studies, performed by means of in situ hybridization and DNA probe analysis, did not demonstrate deletion in the Miller‐Dieker/isolated Lissencephaly critical region on the short arm of chromosome 17. © 1993 Wiley‐Liss, Inc.
Multiple pterygium syndrome with body asymmetry
Authors: Willems Patrick J. , Colpaert Cecile , Vaerenbergh Myriam , Van Thienen Marie‐Noëlle , Parizel Paul M. , Van Marck Eric , Schuerwegh Walter H. , Martin Jean‐Jecques
Published: June 2005

We report on a fetus with multiple pterygia in the popliteal, antecubital, intercrural, axillary, and nuchal region, arthrogryposis, camptodactyly, anal atresia, hypospadias, ambiguous genitalia, and neonatal death. Arthrogryposis was much more pronounced at the left than at the right side. Moreover, there was gross body asymmetry with hypoplasia of the left arm, leg, pelvis, and kidney.

As this spectrum of anomalies does not fit any of the known multiple pterygium syndromes, this patient adds another clinical entity to the already wide spectrum of multiple pterygium syndromes. © 1993 Wiley‐Liss, Inc.
VACTERL with hydrocephalus: Spontaneous chromosome breakage and rearrangement in a family showing apparent sex‐linked recessive inheritance
Authors: Wang Hungshu , Hunter Alasdair G. W. , Clifford Brian , McLaughlin Margaret , Thompson Diane
Published: June 2005

The rate of spontaneous and mitomycin C induced chromosome breakage and sister chromatid exchange (SCE) was studied in three related cases diagnosed with VACTERL‐H syndrome. There have been recent reports of sporadic patients with VACTERL‐H in whom high rates of chromosome breakage were observed. This has led to the suggestion that some of these patients may represent the severe expression of Fanconi anemia. The pattern of inheritance in our family is highly suggestive of X‐linked recessive inheritance supporting the hypothesis that VACTERL‐H is, at least in some cases, a syndrome and not an association. © 1993 Wiley‐Liss, Inc.
Julia Pastrana, the nondescript: An example of congenital, generalized hypertrichosis terminalis with gingival hyperplasia
Authors: Licsc Jan Bondeson , Miles A. E. W.
Published: June 2005

Julia Pastrana (1834–1860) has gained immortality as one of the most extreme cases of generalized hypertrichosis upon record. When she was exhibited for money in the United States and Europe during the years 1855–1860, people thronged to see her, and she was several times described in the medical press of the day. After Julia Pastrana's death in childbirth, her corpse was embalmed in a very life‐like manner, and exhibited all over Europe for several decades. Later, the mummy was believed to be lost, but in 1990 it was discovered at the Oslo Forensic Institute. Some writers have included Julia Pastrana among the cases of congenital hypertrichosis languinosa. However, a microscopic examination of hair samples from the mummy shows that her hairy growth is unmistakably terminal in character, and we propose that she instead was an example of congenital, generalized hypertrichosis terminalis with associated gingival hyperplasia. While many earlier writers have asserted that Julia Pastrana's dentition was abnormal, a radiographic examination of the mummy has shown that she had a complete permanent dentition. © 1993 Wiley‐Liss, Inc.
Screening for carriers of Tay‐Sachs disease in the ultraorthodox Ashkenazi Jewish community in Israel
Authors: Broide Etty , Zeigler Marcia , Eckstein Joseph , Bach Gideon
Published: June 2005

A screening program for the detection of Tay‐Sachs disease (TSD) carriers in the ultra Orthodox community of Ashkenazi Jews has operated in Israel since 1986. The purpose of this program is the prevention of marriages of 2 heterozygotes. The screened individuals are mostly couples in the engagement process or students in religious high schools. Two mandatory requirements guide this program. First, anonymity of the tested individuals who are identified only by code numbers; second completion of the test results of couples in the engagement process within a few days. The screening program is performed by the determination of hexosaminidase A (Hex A) activity in serum which is repeated in serum and leukocyte extracts in couples where both partners were found in the heterozygote range in the initial tests.

The minimal carrier frequency was estimated to be 1:26 or higher, which is higher then in the general Jewish Ashkenazi population. This higher carrier frequency apparently stems from the fact that most members of this community originate from central Europe where the TSD carrier frequency was previously reported to be the highest in the Ashkenazi population. Since the beginning of the screening program no TSD child has been born to newlywed couples of this community in Israel. © 1993 Wiley‐Liss, Inc.
Terminal deletion of 7q presenting in utero with a truncus arteriosus and nonimmune hydrops
Authors: Finley Brent E. , Seguin John H. , Bennett Timothy L. , Ardinger Robert , Burlbaw Jeannette , Levitch Lenna , Keifer Cathy , Pasztor Linda
Published: June 2005

Terminal deletion of 7q presents with variable anatomical and developmental findings. This case is the first reported in utero diagnosis based on cytogenetic findings and in utero demonstration of resolving congestive heart failure due to a truncus arteriosus. © 1993 Wiley‐Liss, Inc.
Clarification of subtle reciprocal rearrangements using fluorescence in situ hybridization
Authors: Sullivan Beth A. , Leana‐Cox Julie , Schwartz Stuart
Published: June 2005

Fluorescence in situ hybridization (FISH) using chromosome‐specific DNA libraries as painting probes was applied in the analysis of six subtle, balanced chromosome rearrangements. Both fresh and older slides, some of which had been previously G‐banded, were used to determine if FISH could identify unambiguously very small amounts of translocated material. Our results indicate that this procedure can clearly and precisely distinguish the specific components of extremely subtle translocations, in different cell types, such as leukocytes, aminocytes, and chorionic villus, and irregardless of preparation age. This ability makes FISH a valuable tool in clinical cytogenetics for the confirmation of preliminary G‐banded karyotypes. © 1993 Wiley‐Liss, Inc.
Carpenter syndrome with normal intelligence: Brazilian girl born to consanguineous parents
Authors: Richieri‐Costa A. , Pirolo L. , Cohen M. M.
Published: June 2005

We report on a Brazilian girl with Carpenter syndrome born to consanguineous parents. She had normal neuropsychological development, postnatal overgrowth, and oligodontia of the permanent teeth. Clinical and genetic aspects are discussed. © 1993 Wiley‐Liss, Inc.
Two siblings with midline field defects and Hirschsprung disease: Variable expression of Toriello‐Carey or new syndrome?
Authors: Jespers A. , Buntinx I. , Melis K. , Vaerenberg M. , Janssens G.
Published: June 2005

We describe 2 sibs with multiple congenital anomalies. The main manifestations include hypoplasia of the corpus callosum and/or cerebellar hypoplasia, Robin sequence, pharyngeal and laryngeal hypoplasia, abnormal ears, excessive neck skin, cardiac defect, and Hirschsprung disease. The presence in 2 sibs born to healthy, consanguineous parents suggests autosomal recessive inheritance. These anomalies must have arisen during blastogenesis; the syndrome resembles most the condition described in 1988 by Toriello and Carey (Am J Med Genet 31:17–23). © 1993 Wiley‐Liss, Inc.
Familial pallister‐hall syndrome: Case report and hormonal evaluation
Authors: Sills Irene N. , Rapaport Robert , Robinson L. Pat , Leiber Caroline , Shih Ling Yu , Horlick Mary N. B. , Schwartz Malcolm , Desposito Franklin
Published: June 2005

Pallister‐Hall syndrome is a usually lethal dysplasia/malformation syndrome characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial polydactyly, craniofacial malformations, imperforate anus, and other malformations. We report a familial case in a male infant and his female sib fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an autosomal dominant mutation, or a segregating submicroscopic chromosome abnormality. Detailed endocrine evaluation on the surviving infant revealed documented pituitary function, pituitary deficit, and hypothalamic deficiency. We suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in pallister‐Hall syndrome. © 1993 Wiley‐Liss, Inc.
Reproductive failure in a patient with neurofibromatosis‐noonan syndrome
Authors: Meschede Dieter , Froster Ursula G. , Gullotta Filippo , Nieschlag Eberhard
Published: June 2005

We report on a 39‐year‐old man with neurofibromatosis‐Noonan syndrome and longstanding infertility. Comprehensive testing did not uncover any significant endocrine abnormalities, but the testicular seminiferous epithelium was found to be severely compromised. While the occasional association of neurofibromatosis with signs of Noonan syndrome has been reported, reproductive failure has not been previously described in this condition. © 1993 Wiley‐Liss, Inc.
Interstitial Duplication of 7(q22→q34)
Authors: Stratton Robert F. , Dupont Barbara R. , Mattern Vicki L. , Schelonka Robert L. , Moore Charleen M.
Published: June 2005

We report on a 3‐year‐old boy with an interstitial duplication of 7(q22→q34), confirmed with fluorescent in‐situ hybridization. He had post‐natal growth retardation, developmental delay, frontal and parietal bossing, deep‐set eyes, strabismus, bilateral optic nerve hypoplasia, and mild dilatation of the cerebral ventricles. His Phenotype was not significantly different from that of the three previously reported patients with interstitial duplication of the smaller segment 7(q22→q31). © 1993 Wiley‐Liss, Inc.
Autosomal imbalance syndromes: Genetic interactions and the origin of congenital malformations in aneuploidy syndromes
Authors: Lurie Iosif W.
Published: June 2005

In some autosomal imbalance syndromes an additional imbalance interferes with the occurrence of the anomalies typical of the syndrome itself. For example, polydactyly was found in patients with “pure” del(3p) more frequently (11/23) than in patients where these deletions were associated with different partial trisomies (2/28). The opposite situation was shown in del(7q) syndrome where various defects of the holoprosencephalic group were found to be rarer in patients with “pure” deletions, than in cases with simultaneous occurrence of various partial trisomies. It suggests the importance of gene interaction in determining the phenotypic picture of autosomal imbalance syndromes. © 1993 Wiley‐Liss, Inc.
Prenatal diagnosis of nonrhizomelic chondrodysplasiapunctata (Conradi‐Hünermann syndrome)
Authors: Pryde Peter G. , Bawle Erawati , Brandt Francisco , Romero Roberto , Treadwell Marjorie C. , Evans Mark I.
Published: June 2005

Chondrodysplasia punctata has been classified into two major types including the rare autosomal recessive “rhizomelic type” and a more common but genetically heterogenous nonrhizomelic type (referrred to by some authors as “Sonradi‐Hünermann (CH) type”). The former is typically lethal, manifesting serious anomalies, and allowing several instances of confident prenatal diagnosis. The latter being milder has more subtle anomalies and prenatal diagnosis has been uncommonly reported (confined to cases diagnosed incidentally by flat‐plate X‐ray examination of the mother in late third trimester, and a case found by directed ultrasound performed in a mandelian affected mother). Cases included (1) a young primigravida thought to be affected with Conradi‐Hünermann syndrome presented at 16 weeks gestation for prenatal diagnosis and counseling. Ultrasound examination of the fetus detected assymetric limb shortness allowing the presumptive diagnosis of an affected fetus which was confirmed after delivery near term. (2) A normal 38‐year‐old multipara with unremarkable family history underwent routine fetal ultrasound evaluation at 18 weeks gestation. Disorganization of the spine, premature echogenicity of femorl epipheses, and frontal bossing with depressed nasal bridge were described. Neonatal examination confirmed suspicion of CH. Case 1 demonstrates the importance of solid clinical diagnosis in Mendelian malformation‐affected parents for directing prenatal diagnostic efforts. Case 2 represents the first index case of CH diagnosed antenatally by ultrasound. Diagnostic clues which must be considered in establishing these diagnoses are discussed, as are some of the difficulties and limitations in antenatal counseling such cases. © 1993 Wiley‐Liss, Inc.
Prenatal diagnosis of Charcot‐Marie‐Tooth disease type 1a by multicolor in situ hybridization
Authors: Lebo Roger V. , Martelli Lucia , Su Ying , Li Lanying , Lynch Eric , Mansfield Elaine , Pua Kong‐Hu , Watson Daniel F. , Chueh Jane , Hurko Orest
Published: June 2005

Genetic heterogeneity within the most common genetic neuropathy, Charcot‐Marie‐Tooth disease (CMT) result in about 70% slow nerve conduction CMT1 and 30% normal nerve conduction CMT2. Autosomal dominant CMT1A on chromosome 17p11.2 represents about 70% of CMT1 cases and about 50% of all CMT cases. Three different size CMT1A duplications with variable flanking breakpoints were characterized by multicolor in situ hybridization and confirmed by pulsed field gel electrophoresis and quantitative polymerase chain reaction (PCR) amplification. These different size duplications result in the same CMT1A phenotype confirming that trisomy of a normal gene region results in CMT1A. the smallest duplication does not include the 409 locus used previously to screen for CMT1A duplications. Direct analysis of interphase nuclei from fetuses and at‐risk patients by multicolor in situ hybridization to a commonly duplicated CMT1A probe is informative more often than polymorphic PCR analysis, faster than pulsed field gel electrophoresis (PFGE), and faster, more informative, and more reliable than restriction enzyme analysis. CMT1B restriction enzyme analysis of CMT pedigrees without CMT1A is expected to diagnose another 8% of at‐risk CMT1 patients (total: 78%). © 1993 Wiley‐Liss, Inc.
Is there a relationship between inborn errors of metabolism and extensive mongolian spots?
Authors: Mendez Heirie Miriam Marques , Pinto Laís Izabel Borges , Paskulin Giorgio Adriano , Ricachnevsky NÉLson
Published: June 2005

We report on a case of inborn errors of metabolism in association with extensive Mongolian spots. We suggest that this association may be due to a disequilibrium of metabolism during embryonic development. © 1993 Wiley‐Liss, Inc.
Evaluation of families wherein a single male manifests a phenotype of X‐linked lymphoproliferative disease (XLP)
Authors: Grierson Helen L. , Skare James , Church Joseph , Silberman Teresa , Davis Jack R , Kobrinsky Nathan , McGregor Rebert , Israels Sara , McCarty James , Andrews Lucy G. , Blecha Timothy , Erdman Steve , Obringer Angela , Scharnhorst David , Purtilo David T.
Published: June 2005

The Epstein‐Barr virus (EBV)‐induced diseases of males with X‐linked lymphoproliferative disease (XLP) include fatal infectious mononucleosis (IM), non‐Hodgkin lymphoma (ML), agammaglobulinemia, and aplastic anemia. These phenotypes also occur as sporadic cases in families, and EBV seronegative males in these families must be considered at risk for XLP until they seroconvert normally to EBV. Given that 50% of males inheriting the defective XLP gene die following primary EBV infection, it is vital that they be identified pre‐EBV infection. Here we report result using molecular genetic techniques to provide information as to the relative risks of EBV negative males and potential carrier females in ten families wherein a single male had died of IM. © 1993 Wiley‐Liss, Inc.
Congenital hypothyroidism presenting as apparent spondyloepiphyseal dysplasia
Authors: Eberle Andrea J.
Published: June 2005

An 11‐year‐old boy with short stature, dysplastic epiphyses, and vertebral abnormalities was thought to have spondyloepiphyseal dysplasia. He was subsequently found to have epiphyseal dysplasia secondary to congenital hypothyroidism. The radiographic findings in longstanding congenital hypothyroidism and spondyloepiphyseal dysplasia are compared and a possible mechanism for the dysplasia of hypothyroidism is discussed. © 1993 Wiley‐Liss, Inc.
X‐inactivation pattern in an Ullrich–Turner syndrome patient with a small ring X and normal intelligence
Authors: Zenger‐Hain Julie L. , Wiktor Anne , Goldman Jose , Van Dyke Daniel L. , Weiss Lester
Published: June 2005

In a description of 8 girls who had Ullrich–Turner syndrome (UTS) with a small r(X), mental retardation, and other unusual findings, it was hypothesized that the distinctive phenotype was associated with the loss of the X inactivation center from the r(X) and lack of genetic inactivation of the ring [Van Dyke et al., 1992]. Here, we present a 17‐year‐old young woman with 45,X/46,X,r(X)(?p11q13) mosaicism, Ullrich–Turner syndrome, and normal intelligence. In situ hybridization with the X‐centromere DNA probe DXZ1 (Oncor, Inc., Gaithersburg, MD) was performaed on previously G‐banded slides, and the probe hybridized to the centromere regions of the normal X and the ring. The r(X) appears to be inactivated since a buccal smear demonstrated 5% Barr bodies. Furthermore, DAPI stain and FISH analysis with the X‐centromere DNA probe DXZ1 was employed to distinguish the inactive X from the active X, and verified the presence of a sex chromatin mass in fibroblasts. These observations are consistent with the active‐ring‐X‐and‐mental‐retardation hypothesis since the ring in this patient, although very small, appears to be normally inactivated and she has normal intelligence. © 1993 Wiley‐Liss, Inc.
Clinical, cytogenetic, and molecular evidence for an infant with Smith–Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion
Authors: Zori Roberto T. , Lupski James R. , Heju Zhang , Greenberg Frank , Killian James M. , Gray Brian A. , Driscoll Daniel J. , Patel Pragna I. , Zackowski Joleen L.
Published: June 2005

We describe an infant with del(17) (p11.2p12) whose deleted chromosome was inherited from a mosaic mother. The child had manifestations consistent with Smith–Magenis syndrome. The mother appeared to be of normal intelligence and she had minimal findings of Smith–Magenis syndrome. Separation of chromosome 17 homologues in somatic cell hybrids and molecular studies confirmed the cytogenetic diagnoses and the fact that the mother was mosaic. Furthermore, molecular analysis demonstrated novel breakpoints in this family, with the deletion extending into and completely encompassing the markers duplicated in Charcot‐Marie‐Tooth (CMT) disease. Although this Smith–Magenis syndrome patient is completely deleted for the CMT region, her electrophysiological findings are different from those found in CMT. This is the only reported case of Smith–Magenis syndrome with transmission from a partially affected mosaic mother. Transmission of interstitial deletions from mosaic parents may be more common than thought; therefore, parental chromosomes should be examined when interstitial deletions are identified. © 1993 Wiley‐Liss, Inc.
Natural history of the recombinant (8) syndrome
Authors: Sujansky Eva , Smith Ann C. M. , Prescott Karen E. , Freehauf Cindy L. , Clericuzio Carol , Robinson Arthur
Published: June 2005

The recombinant 8 [Rec(8)] syndrome [rec(8), (8qter→8q22.1::8p23.1→8qter] is due to a parental inv(8)(8pter→8p23.1::8q22.1→8p23.1::8q22.1→8qter). All inv(8) parents we have studied were of Hispanic origin. The Rec(8) phenotype consists of a characteristic set of minor facial anomalies, cardiovascular and other major malformations, and moderate to severe mental retardation. The clinical phenotype is relatively consistent in all published cases; however the natural history of the condition has remained unknown. Retrospective and prospective information on 42 propositi, spanning a period from 5 days to 23 years, allowed us to define the natural history of this syndrome, tabulate the frequency and the evolution of phenotypic abnormalities, and share our experience with different therapeutic approaches. © 1993 Wiley‐Liss, Inc.
DOOR syndrome (deafness, onycho‐osteodystrophy, and mental retardation): A new patient and delineation of neurologic variability among recessive cases
Authors: Lin Henry J. , Kakkis Emil D. , Eteson Donna J. , Lachman Ralph S.
Published: June 2005

We report the seventeenth case of the recessive form of the DOOR syndrome. The parents were Guatemalan and not known to be consanguineous. The patient had developmental delay, severe sensorineural deafness, and abnormal nails and phalanges in the hands and feet. Urinary 2‐oxoglutarate excretion was normal. The patient was among a subset of DOOR syndrome patients may be useful in discussing the prognosis for newly identified cases. © 1993 Wiley‐Liss, Inc.
Malformations and minor anomalies in non‐trisomic, autosomal aneuploidy
Authors: Cunniff Christopher , Pope Sandra K.
Published: June 2005

We examined the medical records of 43 individuals with non‐trisomic, autosomal aneuploidy evaluated by the Arkansas Genetics Program. Birthweight and the presence of malformations and minor anomalies by organ system were analyzed on each patient. Low birthweight was present in 28% (N = 12) of the patients, 72% (N = 31) of the subjects had a malformation, and 93% (N = 40) had a minor anomaly. Of the entire sample, the most common site of a malformation or minor anomaly was limbs (79%). The most common site of a malformation was the head (21%), eyes (21%), or heart (26%). If a malformation was present, the head was significantly more likely (P<.04) than another body system to be the site of an additional malformation or minor anomaly. A malformation or minor anomaly of the ears was significantly more likely (P<.03) to be present when there was an associated eye anomaly than when no anomaly of the eye was identified. These data have implications for chromosome screening of individuals with malformations or minor anomalies and for the clinical evaluation of those found to have non‐trisomic autosomal aneuploidy. © 1993 Wiley‐Liss, Inc.
Skeletal abnormalities in the Apert syndrome
Authors: Cohen M. Michael , Kreiborg Sven
Published: June 2005

This paper reports on skeletal abnormalities in 38 patients with Apert syndrome. Analysis includes alterations in the shoulders, humeri, elbows, hips, knees, rib cage, and spine (except the cervical spine).

Some patients had subacromial dimples and elbow dimples during infancy. Mobility at the glenohumeral joint was limited. Progressive limitation in abduction, forward flexion, and external rotation with growth was virtually a constant finding. The acromioclavicular joint was prominent and sometimes had an angular, pointed appearance clinically. This was often associated with atrophic musculature and winging of the scapulae. Limited elbow mobility was common and usually mild in degree. Decreased elbow extension was most often found with decreased flexion, pronation, and supination occurring less frequently. Limited elbow mobility did not change significantly with growth in contrast to the increasing severity observed in the shoulder joint. Short humeri were a constant finding beyond infancy and genua valga of mild degree were present in many cases.

Radiographic examination strongly suggests that the Apert syndrome is characterized by a multiple epiphyseal dysplasia. We found delay in appearance of postnatal ossification centers, particularly in the humeral head, greater tuberosity, capitulum, and radial head. Subsequently, these bones became abnormal in shape. Glenoid dysplasia was observed consistently. The neck of the scapula was very short or absent and the inferior margin of the glenoid cavity was poorly demarcated from the infraglenoid tubercle. The humeral head became oblong in shape with relative prominence of the greater tuberosity which compromised abduction. In the elbow, the capitulum was often small and the radial head was flat in many instances. Subluxation or dislocation of the radial head or angulation of the radial neck was observed in some cases. In the hip joint of some adults, the femoral necks were short and broad with prominence of the greater trochanters. Less common radiographic findings are also discussed. © 1993 Wiley‐Liss, Inc.
Evidence for multi‐site closure of the neural tube in humans
Authors: Van Allen Margot I. , Kalousek Dagmar K. , Chernoff Gerold F. , Juriloff Diana , Harris Muriel , McGillivray Barbara C. , Yong Siu‐Li , Langlois Sylvie , Macleod Patrick M. , Chitayat David , Friedman Jan M. , Wilson R. Doug , McFadden Deborah , Pantzar J. , Ritchie Susan , Hall Judith G.
Published: June 2005

Four separate initiation sites for neural tube (NT) fusion have been demonstrated recently in mice and other experimental animals. We evaluated the question of whether the mult‐site model vs. the traditional single‐site model of NT closure provided the best explanation for neural tube defects (NTDs) in humans. Evidence for segmental vs. continuous NT closure was obtained by review of our recent clinical cases of NTDs and previous medical literature.

With the multi‐site NT closure model, we find that the majority of NTDs can be explained by failure of fusion of one of the closures or their contiguous neuropores. We hypothesize that: Anencephaly results from failure of closure 2 for meroacranium and closures 2 and 4 for holoacranium. Spina bifida cystica results from failure of rostral and/or caudal closure 1 fusion. Craniorachischisis results from failure of closures 2,4, and 1. Closure 3 non‐fusion is rare, presenting as a midfacial cleft extending from the upper lip through the frontal area (“facioschisis”). Frontal and parietal cephaloceles occur at the sites of the junctions of the cranial closures 3‐2 and 2–4 (the prosencephalic and mesencephalic neuropores). Occipital cephaloceles result from incomplete membrane fusion of closure 4. In humans, the most caudal NT may have a 5th closure site involving L2 to S2. Closure below S2 is by secondary neurulation.

Evidence for multi‐site NT closure is apparent in clinical cases of NTDs, as well as in previous epidemiological studies, empiric recurrence risk studies, and pathological studies. Genetic variations of NT closures sites occur in mice and are evident in humans, e.g., familial NTDs with Sikh heritage (closure 4 and rostral 1), Meckel‐Gruber syndrome (closure 4), and Walker‐Warburg syndrome (2–4 neuropore, closure 4). Environmental and teratogenic exposures frequently affect specific closure sites, e.g., folate deficiency (closures 2, 4, and caudal 1) and valproic acid (closure 5 and canalization).

Classification of NTDs by closure site is recommended for all studies of NTDs in humans. We conclude that (1) multi‐site NT closure provides the best explanation for NTDs in humans; (2) closure sites are most likely controlled by separate genes expressed during embryogenesis, and variations in rate and location of closures would make embryos more susceptible to environmental and other factors; (3) homologies between the mouse and human genomes may allow linkage studies to be done for families with recurrence of NTDs; and (4) recurrence risks and associated anomalies vary between closure sites, so that more accurate genetic counselling can be given based on the location of the NTD(s) in the proband(s). © 1993 Wiley‐Liss, Inc.
Short rib‐polydactyly syndrome (SRPS) with anencephaly and other central nervous system anomalies: A new type of SRPS or a more severe expression of a known SRPS entity?
Authors: Martínez‐Frías MaríA‐Luisa , Bermejo Eva , Urioste Miguel , Egüés Javier , Soler José A. LÓPez
Published: June 2005

We describe two patients with short rib‐poly‐dactyly syndrome (SRPS) from two unrelated Spanish families. These patients present clinical and radiological characteristics that overlap those of the different established types of SRPS. In addition, one patient had anencephaly and the other patient had severe brain abnormalities with a family history of an older sister with anencephaly, and a brother diagnosed with SRPS. This second family is interesting in that the two affected brothers present with different clinical and radiological findings; for example, one had ovoid tibiae and the other did not. This particular family shows that intrafamiliar variation is also observed within SRPS.

It remains unsettled whether these cases might be considered a new type of SRPS or a variant of an established entity or whether the differences between the SRPS represent variability or heterogeneity. Molecular studies may answer this question in the near future. © 1993 Wiley‐Liss, Inc.
Split hand/split foot anomaly in a family segregating a balanced translocation with breakpoint on 7q22.1
Authors: Genuardi Maurizio , Pomponi Maria Grazia , Sammito Vincenza , Bellussi Angelo , Zollino Marcella , Neri Giovanni
Published: June 2005

An apparently balanced translocation, t(2;7)(q21.1;q22.1) was detected in a female patient with bilateral split hand and right split foot. Split hand/split foot (SHSF) segregated as an autosomal dominant character with low penetrance in her family. The translocation was present in 6 of 13 additional relatives investigated, one of whom also had split hand on right. This observation provides further confirmation of the presence of a locus for SHSF on 7q and narrows the critical region to band 7q22.1. Defects caused by alterations of this chromosome region are variable and include manifestations of both syndromal and non‐syndromal SHSF. Review of SHSF cases associated with chromosome 7 abnormalities showed a preferential involvement of the lower limbs and of the right side, suggesting the action of locally restricted developmental resistance mechanisms. © 1993 Wiley‐Liss, Inc.
Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna
Authors: Beighton P. , Sujansky E. , Patzak B. , Portele K. A.
Published: June 2005

Skeletal material in the Museum of Pathological Anatomy, Vienna, has been appraised in order to modify existing descriptive designations and to establish diagnoses of specific genetic disorders. In this way osseous material relating to classical genetic syndromes has been identified and will be available for further study.

Among the skeletons of adults in the museum, the following genetic conditions could be diagnosed: achondroplasia, Marfan syndrome, cleidocranial dysostosis, and diaphyseal, aclasia. In adult sisters with dwarfism and a rickety bone disorder, the final diagnosis was uncertain. Infantile bone dysplasias, genetic conditions involving the skull, and malformation syndromes which are all represented in the museum are currently being analyzed. © 1993 Wiley‐Liss, Inc.