bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic criteria for Walker‐Warburg syndrome
Authors: Dobyns William B. , Pagon Roberta A. , Armstrong Dawna , Curry Cynthia J. R. , Greenberg Frank , Grix Arthur , Holmes Lewis B. , Laxova Renata , Michels Virginia V. , Robinow Meinhard , Zimmerman Roberta L. , Opitz John M. , Reynolds James F.
Published: June 2005

Walker‐Warburg syndrome (WWS) is an autosomal recessive disorder manifest by characteristic brain and eye malformations. We reviewed data on 21 of our patients and an additional 42 patients from the literature. From this review, we expand the phenotype to include congenital muscular dystrophy (CMD) and cleft lip and/or palate (CLP), and revise the diagnostic criteria.

Four abnormalities were present in all patients checked for these anomalies: type II lissencephaly (21/21), cerebellar malformation (20/20), retinal malformation (18/18), and CMD (14/14). We propose that these comprise necessary and sufficient diagnostic criteria for WWS. Two other frequently observed abnormalities, ventricular dilatation with or without hydrocephalus (20/21) and anterior chamber malformation (16/21), are helpful but not necessary diagnostic criteria because they were not constant.

All other abnormalities occurred less frequently. Congenital macrocephaly with hydrocephalus (11/19) was more common than congenital microcephaly (3/19). Dandy‐Walker malformation (10/19) was sometimes associated with posterior cephalocele (5/21). Additional abnormalities included slit‐like ventricles (1/21), microphthalmia (8/21), ocular colobomas (3/15), congenital cataracts (7/20), genital anomalies in males (5/8), and CLP (4/21). Median survival in our series was 9 months.

A related autosomal recessive disorder, Fukuyama congenital muscular dystrophy, consists of similar but less severe brain changes and CMD. It differs from WWS because of consistently less frequent and severe cerebellar and retinal abnormalities. We think that WWS is identical to “cerebro‐oculo‐muscular syndrome” and “muscle, eye, and brain disease”.
Predictive testing for Huntington disease: I. Description of a pilot project in British Columbia
Authors: Fox S. , Bloch M. , Fahy M. , Hayden M. R.
Published: June 2005

The discovery of DNA markers linked to the gene causing Huntington disease (HD) has allowed the development of predictive testing programs for persons at‐risk. A pilot program was established in British Columbia in November 1986. Ninetyfive persons are currently enrolled. The major objective of this project is to introduce and evaluate a protocol for the delivery of test results to persons at‐risk for HD. The criteria for entry and details of the psychosocial assessment before and after receiving a modified risk are presented. The guidelines that are developed from this project will have major applications for predictive testing programs for other late onset autosomal dominant disorders.
Prenatal exclusion testing for Huntington disease using the polymerase chain reaction
Authors: McIntosh I. , Curtis Ann , Millan F. A. , Brock D. J. H. , Opitz John M. , Reynolds James F.
Published: June 2005

Prenatal exclusion of Huntington disease (HD) may be carried out by analysis of cosegregating DNA markers on a first‐trimester chorionic villus sample. The conventional Southern blot method is time‐consuming and requires microgram quantities of DNA and milligram quantities of villus tissue. The use of the polymerase chain reaction (PCR) to amplify genomic DNA by a factor of 107 or more makes it possible to do analyses on very small samples in a few hours and without recourse to Southern blotting or hybridization with radioactive probes. We report on a fetus at risk of HD; prenatal testing was carried out by using the PCR to amplify a polymorphic DNA sequence adjacent to the HD locus. The risk of the fetus inheriting the HD gene could not be excluded and the pregnancy was terminated. This represents an example of gene tracking by using amplification of a restriction fragment length polymorphism at some distance from the relevant mutation.
Human cardiac myosin heavy chain gene mapped within chromosome region 14q11.2→q13
Authors: Matsuoka Rumiko , Yoshida Michihiro C. , Kanda Naotoshi , Kimura Misa , Ozasa Hisashi , Takao Atsuyoshi , Opitz John M. , Reynolds James F.
Published: June 2005

Our previous report demonstrated that two human cardiac α‐ and β‐myosin heavy‐chains (MHCs) which correspond to MYH6 and MYH7 respectively, according to Human Gene Mapping nomenclature, were mapped to human chromosome 14 and that human cardiac and skeletal MHC genes do not cosegregate. For further analysis, the regional mapping method was used. DNA from 4 human deletion and 3 human duplication cell lines were prepared for southern blotting, hybridized with human cardiac α‐ and β‐MHC DNA probes, and the hybridization intensity relative to 46,XX or 46,XY DNA was estimated. The results showed that two human cardiac MHC genes segregated with the 14cen→q13 region of the long arm of human chromosome 14. In situ hybridization of 3H‐labeled human cardiac α‐MHC probe to normal human metaphase chromosome independently confirmed this result.
Angelman and Prader‐Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion
Authors: Knoll J. H. M. , Nicholls R. D. , Magenis R. E. , Graham J. M. , Lalande M. , Latt S. A. , Opitz John M. , Reynolds James F.
Published: June 2005

Many Prader‐Willi syndrome (PWS) and Angelman syndrome (AS) patients have a cytogenetic deletion of 15q11q13. While AS and PWS share a similar cytogenetic anomaly, they have very different clinical phenotypes. DNAs from 4 AS patients were examined using 5 chromosome 15q11q13‐ specific cloned DNA segments. With the present level of resolution, the molecular deletions between AS and those previously reported for PWS did not appear to differ. However, in contrast to the paternal inheritance of the deleted chromosome 15 observed in the majority of PWS patients, maternal inheritance of the deleted chromosome 15 was demonstrated in the AS patients by restriction fragment length polymorphisms (RFLPs).
Acrocallosal syndrome in a girl born to consanguineous parents
Authors: Salgado Leonardo J. , Ali Carlos A. , Castilla Eduardo E.
Published: June 2005

The present report describes on a 1‐year‐old girl with macrocephaly, bulging forehead, ocular hypertelorism, antimongoloid palpebral slant, convergent strabismus, atrophy of optic papillae, short philtrum, protruding lips, high‐arched palate, bifid uvula, broad trunk, apparently widely spaced nipples, diastasis recti, small umbilical hernia, tapering fingers, fifth‐finger clinodactyly, postaxial polydactyly of the left hand, and bilateral hallux duplication. Partial agenesis of the corpus callosum and central diffuse cortical cerebral atrophy was documented on computed tomography. Chromosomes were normal. Parents were related as half first cousins. Their previous pregnancy had ended in a miscarriage. We suggest that this patient has an acrocallosal syndrome inherited as an autosomal recessive trait. This supports other recent reports that have considered this entity to differ from Greig cephalopolysyndactyly.
Acrocallosal syndrome: New findings
Authors: Moeschler John B. , Pober Barbara R. , Holmes Lewis B. , Graham John M.
Published: June 2005

We describe a 21‐month‐old girl with typical manifestations of the acrocallosal syndrome of craniofacial anomalies, agenesis of the corpus callosum, hallucal duplication, severe hypotonia, and psychomotor retardation. Our patient also had the Dandy‐Walker malformation, imperforate anus with recto vaginal fistula, hypothalamic dysfunction with hypothyroidism and diabetes insipidus, thick, dysplastic pulmonic valve leaflets, central and obstructive apnea, and pulmonary hypertension. These findings add to the delineation of this syndrome.
Acrocallosal syndrome: Additional manifestations
Authors: Casamassima Anthony C. , Beneck Debra , Gewitz Michael H. , Horowitz Marc A. , Woolf Paul K. , Pettersen Isabel M. , Shapiro Lawrence R.
Published: June 2005

The acrocallosal syndrome (ACS) is a probable autosomal recessive condition of macrocephaly, craniofacial and hand and foot abnormalities, absence of the corpus callosum, and mental retardation. This patient had characteristics of the ACS but also had a severe congenital heart defect and other visceral malformations. After comparing the ACS with and contrasting it to other disorders, we concluded that the internal organ abnormalities found in this patient probably represent further manifestations of the ACS.
Incidence of 15q deletions in the Angelman syndrome: A survey of twelve affected persons
Authors: Williams Charles A. , Gray Brian A. , Hendrickson Jill E. , Stone John W. , Cantú Eduardo S.
Published: June 2005

Prometaphase chromosome study of 12 persons with an established diagnosis of the Angelman syndrome demonstrated that 5 had a 15q12 deletion appearing similar to that commonly observed in the Prader‐Willi syndrome. Phenotype‐karyotype correlation did not show any obvious clinical differences between those with and those without the deletion and no clinical overlap between Angelman and Prader‐Willi syndrome was apparent. Our survey suggests that 15q12 deletions are frequent in Angelman syndrome but presence of the deletion does not appear to distinguish different clinical phenotypes. Experience with the cytogenetic study of Prader‐Willi syndrome predicts that considerable complexity will emerge between the presence of 15 chromosome abnormalities and clinical expression of Angelman syndrome.
Direct duplication of chromosome 1, dir dup(1)(p21.2 → p32) in a Bedouin boy with multiple congenital anomalies
Authors: Mohammed F. M. A. , Farag T. I. , Gunawardana S. S. , Al‐Digashim D. D. , Al‐Awadi S. A. , Al‐Othman S. A. , Sundareshan T. S.
Published: June 2005

Here we describe a Bedouin boy with a de novo duplication of 1p and multiple congenital anomalies. He had microcephaly, convergent squint, anteverted nostrils, malformed ears, micrognathia, hypoplasia of the terminal phalanges, clinodactyly of 5th fingers, simian creases, left inguinal hernia, cryptorchidism, and severe postnatal growth retardation. Our clinical findings are compared with those of previous reports of duplication involving chromosome 1p.
Limb deficiency in an infant with Smith‐Lemli‐Opitz syndrome
Authors: Singer Lewis P. , Marion Robert W. , Li John K. H.
Published: June 2005

We describe a 46,XY newborn infant with Smith‐Lemli‐Opitz syndrome (SLOS) with multiple congenital anomalies including female external genitalia, a testis palpable in each labium majus, a cone‐shaped cervix, and normal vagina. Additional anomalies included cleft palate, total anomalous pulmonary venous return, and striking limb defects (ectrodactyly of the left upper limb, radial aplasia, and monodactyly of the right upper limb). To our knowledge, this is the first report of SLOS associated with limb deficiency and the third associated with total anomalous pulmonary venous return. Our patient demonstrates that limb deficiencies may be a rare component manifestation in this syndrome of multiple congenital anomalies.
Glutaric aciduria type II: Review of the phenotype and report of an unusual glomerulopathy
Authors: Wilson Golder N. , de Chadarévian Jean‐Pierre , Kaplan Paige , Loehr James P. , Frerman Frank E. , Goodman Stephen I.
Published: June 2005

A male infant with glutaric aciduria II secondary to electron transfer flavoprotein: ubiquinone oxidoreductase deficiency is compared to previously reported cases of glutaric aciduria II. A common pattern of anomalies in patients with malformations (8/16) includes macrocephaly, large anterior fontanelle, high forehead, flat nasal bridge, telecanthus, and malformed ears. Abnormalities such as hypotonia, cerebral gliosis, heterotopias, hepatomegaly, hepatic periportal necrosis, polycystic kidneys, and genital defects in glutaric aciduria II are reminiscent of those in Zellweger syndrome, whereas elevations of glutaric, ethylmalonic, adipic, and isovaleric acids are quite distinctive. A unique ultrastructural alteration of the glomerular basement membrane was observed in the proposita. This manifestation may represent an early stage in renal cyst formation and provide a diagnostic criterion for glutaric aciduria II when enzyme studies are unavailable.
Estimate of the proportion of Duchenne muscular dystrophy with autosomal recessive inheritance
Authors: Zatz Mayana , Passos‐Bueno Maria Rita , Rapaport Debora
Published: June 2005

The aim of the present report was to estimate the proportion of autosomal recessive (AR) inheritance among families with affected males diagnosed as Duchenne muscular dystrophy (DMD) in which X‐linked inheritance could not be confirmed. A total of 470 families was studied: 20 with at least one affected girl with “Duchenne‐like” phenotype and 450 with only affected boys. Based on the number of families with at least one affected girl and the number of patients per sibship among these pedigrees, the proportion of families with DMD inherited as an AR trait was estimated at 6.8%. It is also estimated that 2.5–4% of male isolated patients diagnosed as DMD may have the AR form, which could be one possible explanation for the inconsistent results between clinical diagnosis and dystrophin assessment in one case recently reported.
Multibranched chromosomes in the ICF syndrome: Immunodeficiency, centromeric instability, and facial anomalies
Authors: Turleau Catherine , Cabanis Marie‐Odile , Girault Danièle , Ledeist Françoise , Mettey René , Puissant Hugues , Prieur Marguerite , De Grouchy Jean
Published: June 2005

A new patient with the rare ICF syndrome (immunodeficiency, centromeric heterochromatin instability, and facial anomalies) is reported. The six patients previously reported in the literature are reviewed. The main clinical and cytogenetic characteristics of the syndrome are discussed.
Further delineation of the Nijmegen breakage syndrome
Authors: Taalman Rob D. F. M. , Hustinx Theo W. J. , Weemaes Corry M. R. , Seemanová Eva , Schmidt Angela , Passarge Eberhard , Scheres Jacques M. J. C.
Published: June 2005

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a “bird‐like” face, immunological defects involving both the humoral and the cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X‐rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X‐irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha‐fetoprotein level in their serum is normal.
Microscopic study of holoprosencephalic facial anomalies in trisomy 13 fetuses
Authors: Sperber G. H. , Honoré L. H. , Machin G. A.
Published: June 2005

The cerebral and facial anatomy of four trisomy 13 fetuses was studied in order to delineate the varying degrees of expression of severity of holoprosencephaly. Fetal heads were serially sectioned and analyzed microscopically in the horizontal plane. Examples of cyclopia, cebocephaly, and a proposed new category, premaxillary dysgenesis, were studied. The last category represents the least severe end of the facial spectrum of holoprosencephaly in this series. In this condition, there are deficiencies or clefts within the premaxilla, in contrast to the usual site of clefting between the maxilla and the premaxilla. There is asymmetry of the defects in the anterior midface of all four cases.
Polyasplenia complex with mesocardia and renal agenesis in an infant of a diabetic mother
Authors: Gonzalez Alfonso , Krassikoff Natalie , Gilbert‐Barness Enid F.
Published: June 2005

Despite improved prenatal care, infants of diabetic mothers (IDM) have an increased risk of congenital malformations. We report on an IDM with multiple congenital anomalies consistent with the polyasplenia complex with associated mesocardia and renal agenesis. The morphologic characteristics of these malformations are discussed. Special emphasis is given to the polyasplenia complex as an example of midline developmental field defect. The importance of maternal levels of hemoglobin A1c in relation to congenital malformations is addressed.
Gaucher disease type I and pregnancy
Authors: Zlotogora J. , Sagi M. , Zeigler M. , Bach G.
Published: June 2005

We surveyed 47 pregnancies of 17 women affected with Gaucher disease (GD) type I. In two women affected with the severe form of GD type I, no change was observed in the course of the disease during pregnancy. In one patient with the moderate form of the disease there was an exacerbation of the disease during and after pregnancy, and thereafter two subsequent pregnancies of this woman ended by early spontaneous abortion. Four women were diagnosed during their pregnancy or soon after delivery suggesting in these women an exacerbation related to pregnancy. In the other ten women there was no change in the course of the disease. In general, the pregnancies of women affected with GD were normal; however, six women needed blood transfusion during pregnancy or at delivery. From these data it is suggested that there is some risk to pregnant women affected with GD type I, and accordingly, appropriate follow‐up should be planned at the beginning of pregnancy in these patients.
Tricho‐rhino‐phalangeal and branchio‐oto syndromes in a family with an inherited rearrangement of chromosome 8q
Authors: Haan E. A. , Hull Y. J. , White S. , Cockington R. , Charlton P. , Callen D. F.
Published: June 2005

Here we report on a family with an inherited rearrangement of chromosome 8q, dir ins(8)(q24.11q13.3q21.13). Individuals with the chromosome abnormality, which does not appear to be associated with deletion of chromosome material, have manifestations of both tricho‐rhino‐phalangeal syndrome (TRPS) and branchio‐oto syndrome (BOS). TRPS has been linked previously to deletions involving 8q24.11→q24.13, but none of the described patients with deletions in this part of 8q have had characteristics of the BOS. The presence of a breakpoint in 8q24.11 without apparent chromosome deletion in the family described suggests that TRPS maps to this band of 8q. Further, it is suggested that BOS maps to either 8q13.3 or 8q21.13.
Prometaphase chromosomes in the tricho‐rhino‐phalangeal syndrome type I
Authors: Yamamoto Yoshifumi , Oguro Noriko , Miyao Masutomo , Yanagisawa Masayoshi , Ohsawa Tadashi
Published: June 2005

Prometaphase chromosome analysis was undertaken in a patient with familial tricho‐rhino‐phalangeal syndrome type I (TRPS‐I). The patient had apparently normal chromosomes and produced counterevidence to part of Bühler's hypothesis. Thus, although some cases of typical TRPS‐I may be derived from a deletion of 8q24.12, others might be caused by gene mutation or submicroscopic deletion involving the corresponding locus within the band 8q24.11 → 24.13.
Wisconsin consanguinity studies. II: Familial adenocarcinomatosis
Authors: Lebel Robert Roger , Gallagher William B.
Published: June 2005

Predisposition to carcinoma in certain families has been recognized as an autosomal dominant trait. We describe a large pedigree (over 1,000 persons) including ten consanguineous unions with inbreeding coefficients from 0.02 to 0.17. Persons of consanguineous parentage accounted for 16 of 18 cases of adenocarcinoma (most of which were colorectal). Three women with breast cancer were relatives but not of consanguineous parentage. Only six of 36 persons with a malignancy of any kind were unrelated spouses, and only one of these had adenocarcinoma. Multiple primary carcinomas and/or early age‐of‐onset were observed only in products of consanguinity. In this extended family, the occurrence of adenocarcinoma appears to segregate as an autosomal recessive trait. It is conceivable that a proto‐oncogene is segregating in this family and that, in some members, consanguineous unions have produced homozygosity for this oncogene.
Optic atrophy, hearing loss, and peripheral neuropathy
Authors: Hagemoser Kristal , Weinstein Joel , Bresnick George , Nellis Robert , Kirkpatrick Susan , Pauli Richard M.
Published: June 2005

Here we report on two families with a previously apparently undescribed, autosomal dominant disorder resulting in optic atrophy and subsequent development of hearing loss and peripheral neuropathy. This disorder differs from previous syndromes resulting in this triad of effects both in the severity and early onset of the optic atrophy and in its mode of transmission. Review of published cases of optic atrophy + hearing loss + peripheral neuropathy suggests that there are at least three such specific disorders; classification of these published cases by first‐appearing symptom also results in a clean division by most‐likely inheritance.
Male infant with ichthyosis, Kallmann syndrome, chondrodysplasia punctata, and an Xp chromosome deletion
Authors: Bick David , Curry Cynthia J. R. , McGill John R. , Schorderet Daniel F. , Bux Robert C. , Moore Charleen M.
Published: June 2005

We report on a male infant with X‐linked ichthyosis, X‐linked Kallmann syndrome, and X‐linked recessive chondrodysplasia punctata (CPXR). Chromosome analysis showed a terminal deletion with a breakpoint at Xp22.31, inherited maternally. This patient confirms the localization of XLI, XLK, and CPXR to this region of the X chromosome and represents an example of a “contiguous gene syndrome.”

A comparison of the manifestations of patients with CPXR, warfarin embryopathy, and vitamin K epoxide reductase deficiency shows a remarkable similarity. However, vitamin K epoxide reductase deficiency does not appear to be the cause of CPXR. We propose that CPXR may be due to a defect in a vitamin K‐dependent bone protein such as vitamin K‐dependent bone carboxylase, osteocalcin, or matrix Gla protein.
Two infants with del(3)(p25pter) and a review of previously reported cases
Authors: Ramer Jeanette C. , Ladda Roger L. , Frankel Carl
Published: June 2005

Del(3)(p25pter) is associated with a characteristic multiple congenital anomalies/mental retardation syndrome. Early recognition of these manifestations and identification of the chromosome defect are essential for proper management and counseling.
Duchenne muscular dystrophy in monozygotic twins: Deletion of 5′ fragments of the gene
Authors: Lonasescu Victor V. , Searby Charles C. , Ionasescu Rebecca , Patil Shivanand
Published: June 2005

A recombinant DNA study for deletion evaluation was performed in a 4 generation family with Duchenne muscular dystrophy (DMD) in twins. The patients were 6 years old, had a history of progressive difficulty in walking since age 4, and showed weak gluteals, iliopsoas, latissimus dorsi, rhomboids, lower trapezius, sternocleidomastoids, pseudohypertrophic calves, and tight heelcords. Both patients had high serum creatine kinase of 19,000 and 11,000 IU, respectively, and the muscle biopsy of the left vastus lateralis showed dystrophic alterations. Both twins had the same red cell types for ABO, Rh, CDE, MNSs, Kelly, Lewis, Duffy, and Kidd. HLA typing also detected the same antigens in both twins: A2, B44, DR4, and DR5. Cytogenetic studies were consistent with 46, XY male individuals with normal banding pattern. By cDNA probes the entire DMD gene was surveyed for missing or abnormal‐sized restriction fragments. Both twin boys showed absence of 8.5, 8.0, 4.6, 4.2, and 3.1 kb fragments on Hind III blots and absence of 13.5, 3.7, 2.9, and 1.4 kb fragments on Bgl II blots both hybridized with cDNA l‐2a corresponding to most 5′ region of the DMD gene. The mother and other relatives of the patient did not show deletion. These findings strongly suggest that the deletion in the DMD monozygotic twins represents a new mutation.
Trisomy 18 and hepatoblastoma
Authors: Mamlok Viviane , Nichols Myron , Lockhart Lillian , Mamlok Robert
Published: June 2005

A 4‐month‐old girl with trisomy 18 had a congenital heart defect and an hepatoblastoma.
Weaver syndrome: The changing phenotype in an adult
Authors: Greenberg Frank , Wasiewski Warren , McCabe Edward R. B.
Published: June 2005

We report on a 25‐year‐old woman who was diagnosed with Weaver syndrome after reevaluation because of the family's concern regarding recurrence risk for mental retardation in offspring of the woman's brother. The diagnosis was suggested on the basis of postnatal growth excess, camptodactyly, and developmental delay, but with a somewhat atypical facial appearance. When childhood photographs were reviewed, her facial characteristics were more consistent with those of Weaver syndrome in early childhood, but became less obvious with age. This is the second adult reported with Weaver syndrome and provides documentation of the adult phenotype. The diagnosis may be more difficult to make in adolescents and adults if one uses criteria developed for facial manifestations in young children.
Validity of cytogenetic analyses from trophoblast tissue throughout gestation
Authors: Miny Peter , Basaran Seher , Pawlowitzki I. Harry , Horst Jürgen , Westendorp Andre , Niedner Wolfram , Holzgreve Wolfgang
Published: June 2005

Cytogenetic findings in the Münster Chorionic Villi Sampling (CVS) program are presented after 1,184 first trimester transcervical samplings and 131 second and third trimester placentacenteses. In the first trimester series the abnormality rate is low (2.4%) in patients with only an age‐dependent aneuploidy risk. In this group terminations were performed in only 1.6% because of aneuploidy. True mosaicism was found more frequently after CVS, and the risk of maternal cell contamination seems higher as compared to amniocentesis. There are no obvious differences in the overall rate of diagnostic errors after both procedures, when metaphases after direct preparation and chorionic cell cultures are analysed and doubtful findings such as mosaicism are adequately followed up by amniocentesis. The cytogenetic techniques also offer a very rapid approach to karyotyping in the second and third trimester. We found a high rate of aneuploidy (15%) when placentacentesis was performed after sonographic diagnosis of fetal abnormalities. We conclude that cytogenetic analysis from trophoblast tissue is an accurate diagnostic tool applicable from first to third trimester of pregnancy.
Two rare developmental defects of the lower limbs with confirmation of the lewin and opitz hypothesis on the fibular and tibial developmental fields
Authors: Pavone Lorenzo , Viljoen Denis , Ardito Salvatore , Rizzo Renata , Neri Giovanni , Longo Gianfranco , Beighton Peter
Published: June 2005

We report on two unrelated patients with malformations of the lower limbs. One had a unilateral apparent doubling of the volume of the femur with distal bifurcation, shortness of the tibiae, absence of fibulae, and lateral ray deficiencies of both feet. The other had a partial duplication of the distal left femur, hypoplasia and proximal dislocation of the ipsilateral tibia, syndactyly of the right 1st and 2nd toes, and preaxial polydactyly of the left foot. This report supports the hypothesis of Lewin and Opitz on the presence of two distinct fields of development: the fibular and the tibial.
Humero‐radial synostosis with ulnar defects in sibs
Authors: Ramer Jeanette C. , Ladda Roger L.
Published: June 2005

Sibs with virtually identical humero‐radial synostosis (HRS) are presented and compared with 17 previously reported cases from the literature of recessively transmitted HRS. The range of anomalies described includes (in addition to humero‐radial synostosis) ulnar hypoplasia, patellar hypoplasia, and chronic glomerulo‐nephritis.
Familial uterine hernia syndrome: Report of an Arab family with four affected males
Authors: Naguib Kamal K. , Teebi Ahmad S. , Farag Talaat I. , Al‐Awadi Sadika A. , El‐Khalifa Mohammed Y. , Mahfouz El‐Sayed
Published: June 2005

We report an Arab Bedouin family including four males with uterine hernia syndrome. All had a male chromosome constitution and phenotype, inguinal herniae, cryptochidism, and persistence of Müllerian derivatives. Histopathological studies confirmed the presence of both testicular tissue and Müllerian derivatives. The presence of two affected brothers and two affected maternal uncles suggests X‐linked inheritance. Autosomal recessive determination with male sex limitation is also a possibility based on parental consanguinity in one sibship.
Slowly progressive macrocephaly with hamartomas: A new syndrome?
Authors: Halal Fahed , Silver Kenneth
Published: June 2005

We report on an 8 1/2‐year‐old boy with slowly progressive macrocephaly, psychomotor retardation, multiple subcutaneous angiolipomas, hypertelorism, exotropia, prolonged drooling, cutis marmorata, telangiectasia, congenital heart defect, broad thumbs and great toes, and muscle wasting. The syndrome is similar to the Bannayan‐Zonana syndrome and seems to be inherited as an autosomal dominant trait. The father has partial manifestations of the syndrome.
A case of the Freire‐Maia odontotrichomelic syndrome: Nosology with EEC syndrome
Authors: Pavone Lorenzo , Rizzo Renata , Tiné Alessandra , Micali Giuseppe , Sorge Giovanni , Neri Giovanni
Published: June 2005

We report on a patient, born to consanguineous parents, who had a complex malformation syndrome of severe upper limbs anomalies, peculiar face, structural ear anomalies, nasolacrima1 duct obstruction, and abnormal hair and nails. We think that the clinical manifestations of the patient are similar to those described by Freire‐Maia as the odontotrichomelic syndrome; the differential diagnosis between thissyndrome and ectrodactyly, ectodermal dysplasia, and cleft/lip palate (EEC) syndrome is discussed.
Bilateral renal agenesis and Mullerian anomalies in a 47,XXX fetus
Authors: Hogge W. Allen , Vick Dan J. , Schnatterly Patricia A. , MacMillan R. Hunt
Published: June 2005

Congenital absence of the kidneys (bilateral renal agenesis, BRA) is a genetically heterogeneous condition, and all modes of inheritance have been suggested as causes. The finding of a 47,XXX chromosome constitution in a fetus with BRA and developmental arrest of the mesonephric and paramesonephric systems raises the possibility that X chromosome trisomy also may cause the urogenital adysplasia sequence.
“Acadian” and “classical” forms of Friedreich ataxia are most probably caused by mutations at the same locus
Authors: Keats Bronya J. B. , Ward Laura J. , Shaw Jacqui , Wickremasinghe Aranda , Chamberlain Susan
Published: June 2005

“Acadian ataxia” is a form of Friedreich ataxia found in individuals of Acadian ancestry. It was described by Barbeau (in Sobue I (ed): Spinocerebellar Degeneration; Tokyo: Univ. Tokyo Press, pp 121‐142, 1980) as having a slower course of degeneration and less severe secondary symptoms than “classical” Friedreich ataxia. He suggested that these 2 forms of the disease may be distinct. The mutation causing “classical” Friedreich ataxia has recently been mapped to chromosome 9 through genetic linkage studies, and here we show that the locus causing Friedreich ataxia in Acadian families from southwestern Louisiana is tightly linked to the same DNA marker, D9S15. Thus, these 2 disorders, which may be differentiated clinically, are most probably due to mutation(s) at the same locus on chromosome 9.
A new lethal brittle bone syndrome with increased amount of type V collagen in a patient
Authors: Bonaventure Jacky , Zylberberg Louise , Cohen‐Solal Lola , Allain Jean‐Claude , Lasselin Catherine , Maroteaux Pierre
Published: June 2005

A new lethal brittle bone disease is described in three patients with slender long bones, thin ribs, hypomineralized calvaria, and normal facial appearance. In spite of several limb fractures this syndrome can be differentiated from the lethal forms of osteogenesis imperfecta and is better related to the thin‐bone group of lethal dysplasias. Biochemical investigation of collagen from one of the patients by the use of gel electrophoresis and high‐pressure liquid chromatography analyses failed to demonstrate any evident defect in the structure of type I collagen chains. Nevertheless collagen extractability from the dermis was altered owing to an increase in the proportion of acid‐soluble material. Tritium‐proline labeling of cultured fibroblasts confirmed the reduction in total collagen synthesis. This was attributed to a lower type I and type III amount whereas type V collagen level was markedly increased in the cell layer. RNA analysis of the three collagen types with the appropriate cDNA probes confirmed the protein data.

Electron microscopic examination of bone and skin showed morphologically abnormal fibroblasts and osteoblasts with an abundant distended rough endoplasmic reticulum and an altered plasma membrane. Unexpected thin fibrils with a banding pattern and surrounding the type I fibrils were observed. They might represent type V collagen. We suggest that, in this patient, the moderate decrease in type I collagen amount is insufficient to account for the radiological findings and that type V collagen overproduction could play a role in the bone brittleness by interfering with the process of mineralization.
Emerging phenotype of duplication (7p): A report of three cases and review of the literature
Authors: Milunsky Jeffrey M. , Wyandt Herman E. , Milunsky Aubrey
Published: June 2005

Here we report on three patients with dup (7p) and review the previously published 17 cases. Characteristic manifestations include severe/profound psychomotor retardation, dolicho‐cephaly or microbrachycephaly, gaping fontanels and wide sagittal and metopic sutures, hypertelorism, large apparently low‐set ears, micrognathia, choanal atresia/stenosis, hyper‐extensible joints subject to dislocation, joint contractures, and a high rate of cardiac septal defects. Our analysis suggests that dup(7p) is associated with a recognizable characteristic phenotype.
Characterization of an unusual and complex chromosome 21 rearrangement using somatic cell genetics and cloned DNA probes
Authors: Van Keuren Margaret L. , Stewart Gordon D. , Bradley Cynthia M. , Kurnit David M. , Neve Rachael L. , Watkins Paul C. , Tanzi Rudolph E. , Gusella James F. , Patterson David
Published: June 2005

In a previous case of a newborn infant with typical Down syndrome, chromosome analysis indicated the presence of an unusual and complex translocation of chromosome 21. The patient's cells contained one normal chromosome 21 and a rearranged, F group‐sized submeta‐centric chromosome. This abnormal chromosome appeared to involve duplication of the distal portion of 21q with translocation to the short arm, and a deletion of C‐band‐positive centromeric heterochromatin. Using linearly ordered cloned DNA probes, we report the detailed molecular examination of this abnormal chromosome, which has been isolated on a hamster background in a hybrid cell line. Both short arm and pericentromeric sequences are present on this chromosome, as well as distal 21q sequences. However, a substantial portion of proximal 21q is deleted. The distal boundary of this deleted section can be pinpointed within the region between two loci (D21S8 and D21S54), a distance of about 5,000 kb. This study illustrates the power of using precisely mapped, linearly ordered DNA probes to characterize this type of rearrangement. In addition, this hybrid cell line can also be used as a member of a mapping panel to map DNA sequences regionally on chromosome 21.
Prenatal diagnosis of cystic kidney disease with ventriculomegaly: A report of six cases in two related sib ships
Authors: Reuss A , den Hollander J. C. , Niermeijer M. F. , Wladimiroff J. W. , van Diggelen O. P. , Lindhout D. , Los F. J.
Published: June 2005

In 2 consanguineous relationships, a Cape Verdian man fathered six fetuses (5 male) with fetal ventriculomegaly and echodense fetal kidneys as visualized by ultrasonography between 16 and 32 weeks.

During prenatal monitoring, an increased alpha fetoprotein level and abnormal acetyl‐cholinesterase were detected at amniocentesis in 5 of 6 affected fetuses. Chromosomes were normal. Five pregnancies resulted in elective termination; one child was still‐born prematurely. Hydrocephalus and cystic disease of the (renal) cortico medullary areas were found. One fetus had polydactyly. The differential diagnosis and prenatal diagnosis of this presumably autosomal recessive syndrome are discussed.
Cystic hygroma and 45,X/46,XY mosaicism
Authors: Verp Marion S. , Sheikh Zubie , Amarose Anthony P. , Cibils Luis A.
Published: June 2005

We report a case of fetal cystic hygroma with 45,X/46,XY mosaicism.
Acromesomelic dysplasia: Radiologic, clinical, and pathological study
Authors: del Moral Rafael Fernández , Jiménez José M. Santolaya , González José I. Rodríguez , Vicario Ricardo Franco
Published: June 2005

We report a 51‐year‐old woman with aeromesomelic dysplasia. Pathologic studies on adult bone are reported. Hydrocephalus and mild oligophrenia are additional findings.
CFC syndrome: Report on three additional cases
Authors: Sorge Giovanni , Forti Filippo Di , Scarano Gioacchino , Ventruto Valerio , Zelante Leopoldo , Dallapiccola Bruno
Published: June 2005

We describe three patients, originating from three different Italian localities, affected by the cardio‐facio‐cutaneous (CFC) syndrome. In addition to a varying degree of mental retardation, these patients present characteristics consisting of a peculiar face with bitemporal frontal constriction and other anomalies involving the eyes, nose, ears, hair, skin, and heart that are consistent with this diagnosis.
Terminal deletion of the long arm of chromosome 10: Case report and review of the literature
Authors: Gorinati Marino , Zamboni Gaetano , Padoin Nadia , Dodero Andrea , Caufin Daniele , Memo Luigi
Published: June 2005

We report on a newborn girl with a terminal deletion of the long arm of chromosome 10: del (10)(pter→q26). The phenotypic manifestations are compatible with those of the previously reported cases. In addition, the association with abnormalities of the urinary tract is reported for the first time. A clinical and neurodevelopmental follow‐up is described up to age 18 months.
Poland anomaly in mother and daughter
Authors: Cobben Jan M. , Robinson Peter H. , van Essen Antonie J. , van der Wiel Herman L. , ten Kate Leo P.
Published: June 2005

We report on Poland anomaly in a mother and her daughter. Further family history was negative for abnormalities of the hands or the pectoralis major muscle. A review of published cases of familial Poland anomaly is presented. Implications concerning the possible etiology of familial cases of Poland anomaly are given.
Familial abdominal wall defects
Authors: Hershey Douglas W. , Haesslein Hanns C. , Marr Clifford C. , Adkins John C.
Published: June 2005

We report 2 families, each having multiple sibs with abdominal wall defects. In family 1, normal parents gave birth to identical (monochorionic, diamniotic) twins. This is the first reported case of gastroschisis occurring in monozygotic twins. In family 2, a normal mother gave birth to a son with omphalocele. Two subsequent pregnancies with a different husband resulted in a stillborn girl with partial atresia of the colon and a liveborn girl with gastroschisis. In neither case were there any associated anomalies. In neither of the 2 families was there consanguinity or history of other abdominal wall defects. The familial occurrence of these defects suggests that 1) multifactorial determination should be considered in at least some cases of abdominal wall defects, 2) the bowel atresias that occasionally accompany gastroschisis may also have a genetic (multifactorial) cause, and 3) some cases of gastroschisis and omphalocele may have the same genetic cause.
CAMFAK syndrome: A demyelinating inherited disease similar to Cockayne syndrome
Authors: Talwar Dinesh , Smith Stephen A.
Published: June 2005

CAMFAK syndrome is an inherited disease characterized by congenital cataracts, microcephaly, failure to thrive, and kyphoscoliosis with onset in early infancy. Its pathogenesis has not been clearly defined. We report on a patient with this syndrome and present evidence that it is a neurologic disease characterized by peripheral and central demyelination similar to that seen in Cockayne syndrome.
Oliver McFarlane Syndrome: A 25‐year follow‐up
Authors: Sampson J. R. , Tolmie J. L. , Cant J. S.
Published: June 2005

We describe findings in a 29‐year‐old woman with Oliver McFarlane syndrome after 25 years of follow‐up, and we review findings in six other reported cases. Pigmentary retinal degeneration, trichomegaly, prenatal onset growth failure, anterior pituitary deficiencies, and peripheral neuropathy characterize the condition.
Dermatoglyphics in von Recklinghausen neurofibromatosis
Authors: Pallotta Rosanna , Carlone Gaetana , Petrucci Altea , Chiarelli Francesco
Published: June 2005

We studied dermatoglyphic traits in 27 patients (12 males and 15 females) with neurofibromatosis type I (NF‐1) to verify which characteristics may be considered typical of this disorder. The frequency of digital central pockets in the patients was significantly greater than in control individuals (P <.005), but when we evaluated the sexes separately, the difference was significant only among females (P <.002). The distribution of central pockets on the various fingers was significantly different in affected females, compared with normal controls, but only on fingers II (P <.05), IV (P.002), and V (P < .05). The quantitative finger tip pattern values and the total finger ridge count (TFRC) were always higher in the patients, as well as was the a–b ridge count. The latter was significantly increased only on the right hand in females (P < .01). Among the patients, the at̂d angle values were increased on both hands of females and on the right hand in males, whereas both the ulnar index A'‐d and the a‐t' ridge counts were diminished. The frequency of high endings (5′ or 5″) of line A was increased in NF‐1 patients on both hands. Like in previous investigations, our patients showed an increased number of secondary creases, limited to II degree according to Vormittag et al. [1986] (P < .048). Our results only partially confirmed prior data. Therefore, we think that there is no typical dermatoglyphic pattern in NF‐1 and that this parameter is not a diagnostic indicator in this disorder.
Holoprosencephaly and interstitial deletion of 2(p2101p2109)
Authors: Wilson William G. , Shanks Daniel E. , Sudduth Kathryn W. , Couper Kathy A. , McIlhenny Joan
Published: June 2005

We report on a girl with holoprosencephaly and a small, de novo interstitial deletion of most of band 2(p21). The similarity between the cytogenetic findings and CNS malformations in our patient and those recently reported by Münke et al. [Am J Med Genet 30:929–938, 1988] suggests a phenotypic relationship between deletion of this band and holoprosencephaly.
Perspectives on holoprosencephaly: Part III. Spectra, distinctions, continuities, and discontinuities
Authors: Cohen M. Michael
Published: June 2005

This paper attempts to balance our knowledge of holoprosencephalic spectra and continuities with important distinctions and discontinuities. Prevalence studies and syndrome delineation are briefly reviewed. The following topics receive detailed coverage: human teratogens, special aspects of forebrain and hindbrain malformations, aprosencephaly/atelencephaly, association with neural tube defects, current assessment of “facial principles,” and endocrine abnormalities.
BBBG syndrome or opitz syndrome: New family
Authors: Verloes Alain , Le Merrer Martine , Briard Marie‐Louise
Published: June 2005

We report on a family where the propositus had G syndrome, including laryngeal cleft, and another relative had the facial anomalies typical of the BBB syndrome.

We review the literature on the BBB and G syndrome, and argue that no clinical or laboratory criteria permit a differential diagnosis of the two syndromes. Therefore, we suggest that they should be considered variable expression of the same gene. The name BBBG syndrome is proposed for the amalgamated syndrome.
Multiple malformations and exposure to therapeutic ultrasound during organogenesis
Authors: McLeod D. Ross , Fowlow S. B.
Published: June 2005

We present a case of sacral agenesis, microcephaly, and developmental delay. The pregnancy with this child was complicated by left psoas bursitis that was treated by 18 applications of ultrasound between days 6 and 29 of gestation.
Infantile hemangioendothelioma of the liver in patient with interstitial deletion of chromosome 6q: Report of an autopsy case
Authors: Ito Hisao , Yamasaki Takemi , Okamoto Osamu , Tahara Eiichi
Published: June 2005

Here we report an infantile hemangioendothelioma of the liver that developed in a 6 month‐old boy with an interstitial deletion of chromosome 6q. His clinical manifestations included developmental delay, feeding problems, and multiple anomalies including microcephaly, hypertelorism, apparently lowset abnormal ears, prominent nasal bridge, cubitus valgus, overwrapping of fingers, cryptorchidism, and micropenis. He died abruptly at age 27 weeks from a perforating duodenal ulcer. Autopsy demonstrated atrial septal defect, microencephaly, and thymic atrophy. A solitary small tumor was found in the liver and diagnosed histologically as the infantile hemangioendothelioma, type 1. This is the first report of a del(6)q with infantile hemangioendothelioma.
Trisomy 18 at age 21 years
Authors: Smith A. , Field B. , Learoyd B. M.
Published: June 2005

Here we report on a woman with non‐mosaic trisomy 18, who is now 21 years old. She has the characteristic face of older trisomy 18 survivors, marked kyphoscoliosis, spastic quadriplegia with contractures, and profound mental retardation. She has pyorrhea with loss of three canine teeth. At 20.5 years, she had her first menstrual cycle with development of secondary sexual characteristics.
Hydrops revisited: Literature review of 1, 414 cases published in the 1980s
Authors: Machin Geoffrey A.
Published: June 2005

This paper reviews 47 series of hydrops fetalis (804 cases) and 610 individual cases published since 1980. From this large number of cases, guidelines are derived for prenatal diagnosis and management.
Genetic hemochromatosis: Distribution analysis of six laboratory measures of iron metabolism
Authors: Borecki I. B. , Rao D. C. , le Mignon L. , Yaouanq J. , Simon M. , Lalouel J. M.
Published: June 2005

Six laboratory measures of iron metabolism were studied in a control sample, and a family sample was ascertained on the basis of probands with clinically diagnosed genetic hemochromatosis. The respective distribution of each variable evidenced a mixture of components, presumably arising from the segregation of an HLA‐linked locus for hemochromatosis. There were significant differences in the distributional characteristics with respect to sex and genotype‐specific variances. These aspects of the data have important implications for subsequent segregation and linkage analyses, which traditionally assume homoscedasticity and homogeneity of the genetic effect.
Familial duodenal atresia: A report of two families and review
Authors: Best Lyle G. , Wiseman Nathan E. , Chudley Albert E.
Published: June 2005

We report on 2 families with recurrence of uncomplicated duodenal atresia. The presence of consanguinity in one family, the frequent occurrence of consanguinity in parents of affected children previously reported, and the equal sex ratio suggest autosomal recessive inheritance.