bluuebunny/crossref_metadata_2025 huggingface dataset:
Age‐related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population
Authors: Plauchu Henri , De Chadarévian Jean‐Pierre , Bideau Alain , Robert Jacques‐Michel
Published: June 2005

We report the results of a comprehensive and systematic clinical study of 324 patients with hereditary hemorrhagic telangiectasia, selected from a total of 1,270 cases recruited by epidemiological survey. In 94% of the cases, familial occurrence suggested autosomal dominant inheritance; maximum penetrance for at least one manifestation was 97%. Epistaxis was reported by 96% of the patients and, in more than 50%, developed before age 20. Heavy and frequent bleeding occurred mainly in middle‐aged patients. Telangiectasia was documented in 74% of cases, half of whom were younger than 30 years. The frequency of involvement of the hands and wrists was 41%, and for the face, 33%. Visceral involvement was present in 25% of patients, with affected lungs and CNS in the young and gastrointestinal tract and liver in older patients. Symptomatic urinary tract involvement was seen in only two/324 patients. Involvement of other internal sites was not observed.
Congenital microgastria and hypoplastic upper limb anomalies
Authors: Lueder Gregg T. , Fitz‐James Anna , Dowton S. Bruce
Published: June 2005

Six cases of congenital microgastria associated with limb anomalies are reviewed. The microgastria‐hypoplastic upper limb association may arise as a result of aberrant mesodermal development in the 5th embryonic week.
A presumptive translocation 1p;2q resulting in duplication 1p and deletion 2q
Authors: Halal Fahed , Vekemans Michel , Der Kaloustian Vazken M.
Published: June 2005

Here we report on a girl with a translocation between 1 and 2 and duplication 1p and deletion 2q resulting in a multiple congenital anomaly syndrome including intrauterine growth retardation, microcephaly, hypotelorism, cleft palate, subglottic stenosis, umbilical hernia, scoliosis, anal atresia, bilateral calcaneovalgus, overlapping toes, and vertebral anomalies.
Expanding the phenotype of the Proteus syndrome: A severely affected patient with new findings
Authors: Mayatepek Ertan , Kurczynski Thaddeus W. , Ruppert Elizabeth S. , Hennessy James R. , Brinker Ray A. , French Beatrice N.
Published: June 2005

Here we report on a boy who died at 16 1/2 months with hemihypertrophy, eye abnormalities, macrodactyly, hamartomas, pigmented nevi, cerebral involvement, and other anomalies compatible with the Proteus syndrome. In addition, he also had abnormalities previously unreported in the Proteus syndrome including craniosynostosis and complex congenital heart defects. He seems to represent an extremely severe form of the Proteus syndrome and expands the already broad range of the phenotype.
Problems in genetic counseling in a family with an “atypical” centronuclear myopathy
Authors: Müller Bertram , Mostacciuolo Maria Luisa , Danieli Gian Antonio , Grimm Tiemo
Published: June 2005

Genetic counseling often deals with a rare disease the inheritance of which is not clearly established or in which genetic heterogeneity is reported. In addition, relevant parameters such as penetrance, gene frequency, and mutation rate may not be available. In this situation, establishing the risk may be very difficult. An example is presented in which Bayesian risk calculation proved to be of great help in providing precise risk estimates in a family in which an “atypical” centronuclear myopathy was segregating.
Pena‐Shokeir phenotype in sibs with macrocephaly but without growth retardation
Authors: Lammer Edward J. , Donnelly Susan , Holmes Lewis B.
Published: June 2005

A number of more or less distinct subgroups with the Pena‐Shokeir phenotype have been identified. We studied two brothers with the Pena‐Shokeir phenotype who were unusual because they had macrocephaly and normal growth. In the second sib, no neuromuscular abnormalities were found at autopsy. Among the subgroups with Pena‐Shokeir phenotype, these sibs resemble the family reported by Ohlsson et al. [1988] more than the other subgroups that have been proposed. In addition, abnormalities were detected by prenatal ultrasonography during the 18th week of gestation of the second fetus. This finding provides additional evidence that this phenotype may be detected early enough in gestation to consider intervention.
Nonketotic hyperglycinemia in a patient with the 9p– syndrome
Authors: Burton Barbara K. , Pettenati Mark J. , Block Steven M. , Bensen Jeannette , Roach E. Steve
Published: June 2005

We describe a newborn infant with 9p– syndrome and nonketotic hyperglycinemia. This unusual occurrence may not have been coincidental and suggests that there may be a gene for nonketotic hyperglycinemia located on the short arm of chromosome 9.
Chromosome mosaicism in 6,000 amniocenteses
Authors: Wilson Miriam G. , Lin Ming S. , Fujimoto Atsuko , Herbert William , Kaplan Fay M.
Published: June 2005

Multiple cell–multiple flask mosaicism was found in 0.20% of 6,000 amniocenteses, and multiple cell–single flask mosaicism was found in 0.92%. Multiple cell–multiple flask mosaicism usually was found in fetal or infant tissues at delivery or elective abortion.

Most multiple cell–multiple flask mosaicism involved sex chromosomes and was either 45, X/46, XY or 45, X/46, XX. Except for one fetus with 45, X/46, XX and an aortic coarctation, phenotypic abnormalities associated with sex chromosome mosaicism were not found in these patients. One normal boy has continued to show 45,X mosaicism during the first 4 years of life.

Autosome abnormalities found in multiple cell–multiple flask mosaicism included del(18q) associated with fetal anomalies. Apparently normal phenotypes were associated with prenatal trisomy 17, two de novo supernumerary marker chromosomes, and monosomy 21.

Since an aberrant cell line present in only one primary amniotic fluid cell culture was occasionally identified from another amniocentesis or at birth, multiple cell–single flask mosaicism involving a sex chromosome or a viable autosome abnormality cannot be assumed to be an in vitro event.

Maternal cell contamination, which was found in 0.49% of amniocenteses, could have resulted in an erroneous diagnosis of fetal sex in two cases if cells from independent culture vessels were not examined.
Echinogenic action of L‐α‐lysophosphatidylcholine in Duchenne muscular dystrophy: A study on carrier detection
Authors: Tangorra A. , Curatola G. , Milaniy‐Comparetti M. , Ferretti G.
Published: June 2005

The percentage of echinocytes induced after red cell treatment with L‐α‐lysophosphatidylcholine in the blood of 16 patients affected by Duchenne muscular dystropy (DMD) has been evaluated. Moreover, 15 mothers, 10 sisters, and 15 fathers were also included in the study. We found an increased level of echinocytes in dystrophic patients and in known and possible carriers. Correlations were also evaluated between echinocytes and serum enzymes used in DMD diagnosis, showing an increase of echinocytes also in DMD carriers with normal levels of serum creatine kinase, lactate dehydrogenase, and aldolase.

Our results suggest that the sensitivity of erythrocytes to L‐α‐lysophosphatidylcholine in DMD could be used as a diagnostic test for carrier detection.
Sex vesicle “entrapment”: Translocation or nonhomologous recombination of misaligned Yp and Xp as alternative mechanisms for abnormal inheritance of the sex‐determining region
Authors: Stalvey John R. D. , Durbin Edward J. , Erickson Rober T. P.
Published: June 2005

Abnormal inheritance of the sex determining region, normally located on Yp, results in about 1 in 20,000 phenotypic males with a 46,XX genotype. Studies to date indicate that many 46,XX males apparently arise due to a balanced, yet abnormal, nonhomologous interchange of Xp and Yp termini. However, 2 of the 5 XX males we report here have 3 copies of the pseudoautosomal locus, MIC2. Thus, they appear to have inherited the sex determining region as a result of Yp sequences being added onto the X pseudoautosomal region. Such an unequal, extremely nonhomologous interchange could alternatively be considered to arise from an unbalanced translocation of Yp to Xp. Our results suggest that very unequal interchange or translocation of Yp sequences onto the X pseudoautosomal region is not as rare a mechanism for XX males as originally thought. We also suggest that sex vesicle “entrapment” favors the association of a Yp fragment to the X pseudoautosomal region over a translocation to either Xq or an autosome.
Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy
Authors: Clarke J. T. R. , Skomorowski M. A. , Chang P. L.
Published: June 2005

In a child with enzymatically and histopathologically proven metachromatic leukodystrophy (MLD), the disease pursued a course typical of juvenile MLD characterized by neurological degeneration beginning at age 9 years and ending in death at age 18. A younger brother of the patient was found to have profound deficiency of arylsulfatase A in leukocytes and to excrete five‐ to 20‐fold greater than‐normal amounts of sulfatide in the urine. He was completely free of symptoms attributable to MLD until age 16 when he developed acute cholecystitis caused by sulfatide accumulation in the gallbladder. Results of detailed neurological examination at age 21 years were normal; formal psychometric assessment showed a full‐scale IQ of 105 (Wechsler). Studies on cultured skin fibroblasts from the brother showed defects in arylsulfatase A activity, measured with the use of synthetic and natural substrates, and in radiolabeled sulfatide turnover. Cellulose acetate gel electrophoresis of fibroblast extracts from the patient showed no detectable arylsulfatase A isozyme under conditions that clearly distinguished pseudo‐arylsulfatase A deficiency from classical MLD. Biochemically, the patient was indistinguishable from patients with classical MLD; on the other hand, his clinical course is dramatically more benign than that of his sister who was affected with severe MLD.
Quantitative calibration and use of DNA probes for investigating chromosome abnormalities in the Prader‐Willi syndrome
Authors: Tantravahi Umadevi , Nicholls Robert D. , Stroh Helene , Ringer Steven , Neve Rachael L. , Kaplan Lawrence , Wharton Robert , Wurster‐Hill Doris , Graham John M. , Cantú Eduardo S. , Frias Jaime L. , Kousseff Boris G. , Latt Samuel A.
Published: June 2005

Ten genomic DNA probes, subcloned from inserts derived from a phage library constructed from the DNA of flow‐sorted chromosomes, have now been mapped to locations within 15q11–15q13. By dosage blotting and densitometry, 5 of these probes map to the 15q11.2–15q12 segment missing in one 15 chromosome of a Prader‐Willi syndrome (PWS) patient with a prominent cytological deletion. A sixth probe most likely maps to the same region. The other 4 probes map outside of this segment but within 15q11–15q13. Several of the 15q11.2–15q12 probes, and a cDNA probe homologous to one, have been used to test the DNA from 8 patients exhibiting a wide range of the clinical manifestations expected for PWS patients. DNA deletion was observed in all 3 patients with cytological 15q1 deletions as well as in a patient with an unbalanced (Y;15) translocation. DNA from 1 PWS patient with an unbalanced (5; 15) translocation and an inverted duplication of the short arm and proximal long arm of 15 showed at least 1 and possibly 2 extra copies of each genomic probe tested. In the other 3 patients with no cytological deletions, no DNA deletions were found. Thus, the molecular probes described can be used in most PWS patients to analyze the region of proximal 15q implicated in this syndrome.
A syndrome of primary gonadal failure, short stature, mitral valve prolapse, and mental retardation
Authors: Cantalamessa Luigi , Baldini Marina , Ambrosi Bruno , Fraccaro Marco
Published: June 2005

Two brothers referred for hypogonadism presented with short stature, mild mental retardation, and minor anomalies. In addition, both patients had hypogonadism due to primary gonadal failure and mitral valve prolapse, in the absence of other heart defects. A complete hormonal evaluation in one of the patients showed abnormal growth hormone (GH) and gonadotropin responses to different stimuli, findings suggestive of a disorder of hypothalamic‐pituitary regulation. Both patients had normal chromosomes (46,XY) as did their mother (46,XX), who had some of the clinical manifestations found in her sons but in a milder form. We propose that this is a new syndrome.
Autosomal recessive acro‐fronto‐facio‐nasal dysostosis associated with genitourinary anomalies
Authors: Richieri‐Costa A. , Montagnoli L. , Kamiya T. Y.
Published: June 2005

We report a 6‐month‐old boy, born of consanguineous (first‐cousin) parents (F = 1/16) presenting microbrachycephaly, wide forehead, marked hypertelorism, broad nose with a midline groove with a bilateral small “blind dimple” in each side, hypospadias, syndactyly between fingers 3 and 4, broad thumbs, and halluces. This association of anomalies suggests the diagnosis of a “new” type of acrofronto‐facio‐nasal dysostosis. Normal chromosomes, parental consanguinity, and familial occurrence suggest autosomal recessive inheritance.
Johanson‐Blizzard syndrome: Clinical and pathological findings in 2 sibs
Authors: Gould Nevenka S. , Paton John B. , Bennett Angela R.
Published: June 2005

Here we report on 2 sibs with the Johanson‐Blizzard syndrome (JBS). The first child died in the neonatal period, the autopsy showing presence of pancreatic ducts and islets surrounded by connective tissue and a total absence of acini. Morphologic changes suggested dysplasia leading to developmental failure, but early acinar destruction could not be ruled out. The second child had a constellation of abnormalities consistent with JBS, was managed surgically, and is maintained on replacement for his pancreatic enzyme and thyroid hypofunction. At 10 years, he is in a school for the hearing‐impaired and is performing appropriately for his age.
Duplication of 5ql1.2→q13.1 from a familial (5;20) balanced insertion
Authors: Yip Moh‐Ying , Kemp John , Hanson Nils , Wilson Meredith , Purvis‐Smith Stuart , Lam‐Po‐Tang P. R. L.
Published: June 2005

A 2‐year‐old boy with gross motor delay and few minor anomalies has a pure duplication of a small segment of chromosome 5q11.2→q13.1. A balanced insertion of this 5q segment into chromosome 20q proximal to the centromere has been found in his father, uncle, and paternal grandmother.
Terminal deletion 4q in a severely retarded boy
Authors: de Michelena Maria I. , Campos Patricia J.
Published: June 2005

We report a boy with a de novo terminal deletion of chromosome 4q, (q31 → qter) and compare him to 17 previously reported cases with the same anomaly. This case contributes further to the delineation of the del(4)(q31) phenotype, which seems to be clinically recognizable.
Prenatal diagnosis of cystic fibrosis by using linked DNA markers in 138 pregnancies at l‐in‐4 risk
Authors: Feldman G. L. , Lewiston N. , Fernbach S. D. , O'Brien W. E. , Williamson R. , Wainwright B. J. , Beaudet A. L.
Published: June 2005

Prenatal diagnosis was carried out in 138 pregnancies at 1‐in‐4 risk for cystic fibrosis (CF) by using closely linked DNA markers, including XV‐2c and KM‐19. In fully informative families, 25 of 123 (20%) fetuses were predicted to be affected; 16 of these 25 pregnancies were terminated and 9 were continued. Postnatal sweat tests are completed in 42 cases; the diagnoses were confirmed in 4 of 4 infants predicted to be affected and in 37 of 38 infants predicted to be unaffected. One infant predicted to be a carrier had an abnormal sweat test after birth, but the mother also had an abnormal sweat test, and there was no evidence of an error in linkage analysis. The data indicate that prenatal diagnosis using linkage analysis is fully informative in most families and is highly reliable with either chorionic villus sampling or amniocentesis. Although Outcome data are available on only 42 pregnancies, based on our experience, on general principles of linkage of the known DNA markers with CF we recommend that DNA analysis replace microvillar intestinal enzyme analysis for 1‐in‐4 risk pregnancies when DNA is available from the propositus.
Epilepsy and clefting disorders: Lack of evidence of a familial association
Authors: Hecht Jacqueline T. , Annegers J. Fred , Kurland Leonard T.
Published: June 2005

Offspring of women with epilepsy who are taking anticonvulsant medications have an increased incidence of clefting abnormalities. However, there is disagreement as to the extent to which this increase is due to a teratogenic effect of anticonvulsant medications or to a familial association of epilepsy and clefting. Some investigators suggested, but were unable to demonstrate adequately, that clefting and epilepsy associate together in families. In order to address this issue, individuals with a clefting disorder and their relatives were ascertained to determine whether clefting and epilepsy aggregate together in families. The incidence of epilepsy was not increased over that in the general population with a standardized morbidity ratio (SMR) for epilepsy of 0.9 (95% CI 0.2–2.6) for first‐degree relatives (excluding parents) and 0.0 for second‐degree relatives. The SMRs ranged from 0.7–2.2 for the individual relative types (parents 1.5, sibs 0.7, children 2.2) and were also not increased. These results do not support suggestions that clefting and epilepsy segregate together in families.
Estimation of fertility and fitness in Huntington disease in New England
Authors: Mastromauro Carol A. , Meissen Gregory J. , Cupples L. Adrienne , Kiely Dan K. , Berkman Barbara , Myers Richard H.
Published: June 2005

The advent of presymptomatic and prenatal testing in Huntington disease (HD) may change the reproductive behavior of persons at risk for HD. In order to assess future change, an analysis of fertility and reproductive fitness was carried out on 999 affected and 2,253 unaffected offspring from 235 New England families. Ascertainment biases observed for persons born before 1910 and after 1929 reduced the sample to 250 HD cases and 201 unaffected sib controls born between 1910 and 1929.

No increase in reproductive rate was found in HD‐affected men compared to male control sibs. A small increase in fertility averaging 0.5 child was seen in HD‐affected females compared to unaffected females, but this difference was not significant. The increase in mean number of children for HD females is accounted for in part by a small number of affected women who had very large families. No evidence was found to suggest that any increase in reproductive rate for affected persons was related to offspring being born after HD onset. The fitness of both HD‐affected and unaffected females was not significantly different from that of the general population of Massachusetts.
Familial immotile‐cilia syndrome in English springer spaniel dogs
Authors: Edwards David F. , Kennedy John R. , Patton Clark S. , Toal Robert L. , Daniel Gregory B. , Lothrop Clinton D.
Published: June 2005

A laboratory‐maintained colony of English springer spaniel dogs heterozygous for a putative autosomal recessive immotile‐cilia syndrome (ICS) has been studied. Matings between dogs thought to be heterozygous for ICS resulted in 22 pups, five (three males and two females) of which were homozygous for ICS. Four of the five ICS‐affected dogs had chronic rhinitis and bronchopneumonia. The other dog had a serious nasal discharge and died at 10 days. Four dogs had situs inversus totalis (Kartagener syndrome), and the two males of reproductive age were azoospermic. In the two ICS dogs studied for ciliary function, in vivo mucociliary clearance was absent, and in vitro ciliary beat was rarely observed and of low frequency. Scanning and transmission electron microscopy disclosed the same lesions in respiratory cilia from all dogs with ICS, including random orientation and partial outer dynein arm deficiency. Four of five dogs with ICS had dilated lateral ventricles. One female pup with neonatal rhinitis and bronchopneumonia, situs solitus, and dilated lateral ventricles was presumed to be homozygous for ICS, but died without functional or structural confirmation of defective respiratory cilia. An autosomal recessive mode of inheritance for the ciliary defects and respiratory signs of ICS in these dogs is proposed.
Acrofacial dysostoses
Authors: Le Merrer M. , Cikuli M. , Ribier J. , Briard M. L.
Published: June 2005

A female baby was born with phocomelia, bilateral cleft lip and palate, marked micrognathia, malar hypoplasia, absence of lower eyelids, and absence of external ears. Radiological examination showed hypoplastic pectoral and pelvic girdles, short humeri and femora, with absence of forearms and legs, and oligodactyly of upper limbs.

Her mother has triphalangism of the left thumb and a hypoplastic right thumb with stiff metacarpophalangeal joint. She also has downward‐slanting palpebral fissures, malar hypoplasia, and deepset eyes.

This observation offers an opportunity to revisit the acrofacial dysostoses syndromes, including Nager‐Reynier syndrome, Genée‐Wiedeman syndrome, and lethal forms.
Apparently previously undescribed X‐linked dominant syndrome with facial and skeletal anomalies
Authors: Kapur Saroj , Swinford Ann , Freimanis Atis K. , Lachman Ralph S.
Published: June 2005

We report on a syndrome of widow's peak, ptosis, skeletal abnormalities and other minor anomalies in a large family. The condition appears to be inherited in an X‐linked dominant fashion. No similar cases have been found in the literature, suggesting that this is a “new” syndrome. Study of 5 generations of the family documents information on the natural history of the condition.
Autosomal dominant inheritance of the Kabuki make‐up (Niikawa‐Kuroki) syndrome
Authors: Halal Fahed , Gledhill Robert , Dudkiewicz Aaron
Published: June 2005

We report on three individuals (two sibs and their father) with the Kabuki make‐up syndrome. The two sibs had congenital dislocation of the hips and all three individuals had short stature and the facial characteristics of the syndrome. To our knowledge this is the first report of familial occurrence of the Kabuki make‐up syndrome.
Immotile cilia syndrome including polysplenia, situs inversus, and extrahepatic biliary atresia
Authors: Gershoni‐Baruch Ruth , Gottfried Emanuel , Pery Menucha , Sahin Abdala , Etzioni Amos
Published: June 2005

Here we report on 2 sibs with immotile cilia syndrome (ICS), born to consanguineous Arab parents. Both had the Kartagener triad. In addition, one sib had polysplenia and extraheptic biliary atresia. This observation, together with other literature reports, suggests that the occurrence of ICS with polysplenia and extrahepatic biliary atresia represent the result of a single dysmorphogenetic process. It is concluded that polysplenia and extrahepatic biliary atresia are rare and unusual manifestations of ICS.
Nager acrofacial dysostosis: Autosomal dominant inheritance in mild to moderately affected mother and lethally affected phocomelic son
Authors: Hall Bryan D.
Published: June 2005

A mild to moderately affected mother with Nager acrofacial dysostosis produced a severely affected phocomelic son. This apparent autosomal dominant transmission and the extreme variability dictates a reassessment of the genetics of Nager acrofacial dysostosis.
Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen‐genetic heterogeneity in insulin‐dependent diabetes
Authors: Allen David B. , MacDonald Michael J. , Gottschall Jerome L. , Hunter Jay B.
Published: June 2005

It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)‐DR3‐associated allele and an HLA‐DR4‐associated allele in insulin‐dependent diabetes mellitus (IDDM). Equally well established are the association of DR3 with Graves' disease and other autoimmune disorders in nondiabetics and the increased prevalence of autoimmune thyroid disease in IDDM. Perhaps in large part because of these facts, it has been postulated that there are two major forms of classical IDDM—one form characterized by coexistent autoimmune disease, such as autoimmune thyroid disease which is associated with DR3, and another form not associated with additional autoimmune disorders, which is associated with DR4. Several studies have repudiated the idea of specific clinical findings in IDDM being associated exclusively with DR4. However, the DR3‐thyroid association in IDDM has not been investigated carefully. Therefore, in order to study this putative association, we divided a group of diabetic children into overlapping subgroups based on thyroid enlargement, antithyroid microsomal antibodies, acquired hypothyroidism, and no evidence of thyroid disease. The distributions of HLA‐DR3 and ‐DR4 among these subgroups did not differ from each other; nor did the distribution of the HLA alleles differ from those of randomly selected IDDM individuals. These results suggest that thyroid autoimmunity in IDDM is part of the IDDM “syndrome” and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA‐thyroid disease association to support this heterogeneity.
Congenital shortness of the costocoracoid ligament
Authors: Bamforth J. Stephen , Bell Michael H. , Hall Judith G. , Salter Robert B.
Published: June 2005

We report a large kindred in which individuals presented with fixation of the scapula to the first rib by a congenitally short costocoracoid ligament. Cosmetic deformity with rounding of the shoulder and loss of the anterior clavicular contour was the main concern of the affected individuals. Movements requiring rotation or retraction of the scapula were limited, although this did not interfere with normal activities. Surgical treatment consists of excision of the costocoracoid ligament and resulted in some correction of the cosmetic deformity. The pedigree supports an autosomal dominant mode of inheritance with variable expression. The abnormality results in a pectoral girdle which is reminiscent of that seen in the monotremes.
Atypical postaxial acrofacial dysostosis (AFD): Diabetic embryopathy or a new AFD syndrome?
Authors: Richieri‐Costa A. , Guion‐Almeida M. L.
Published: June 2005

We report on a Brazilian girl, born to a diabetic mother, and presenting with atypical pre/postaxial acrofacial dysostosis, nosologically related to the Genée‐Wiedemann syndrome. Clinical and genetic aspects of this acrofacial dysostosis and its relationship to diabetic embryopathy are discussed.
A case of de novo i(12p) with 12q whole‐arm translocation mosaicism
Authors: Marques‐de‐Faria Antonia Paula , Hackel Christine
Published: June 2005

We report a dup(12p) due to a de novo i(12p) in a girl with mosaicism for 12q whole‐arm translocations onto 7p, 7q, and 11q terminal regions. The dup(12p) syndrome was confirmed by clinical, cytogenetic, and LDH‐dosage studies.
Nocturnal rhythm of growth hormone in Duchenne patients: Effect of different doses of mazindol and/or cyproheptadine
Authors: Zatz Mayana , Rapaport Debora , Pavanello Rita C. M. , Rocha Jane M. L. , Vainzof Mariz , Nicolau W.
Published: June 2005

Human growth hormone (hGH) inhibition may be beneficial for Duchenne muscular dystrophy (DMD) patients and slow the rate of progression of the disease. The purpose of the present investigation was 1) to assess, before any therapeutic trial, the natural growth hormone (GH) rhythm during physiological sleep in DMD patients and in normal control boys of comparable age; 2) to evaluate the effect of different doses of two potential GH inhibitors on nocturnal GH secretion in DMD patients receiving mazindol (1–4 mg), cyproheptadine (4–8 mg), or both drugs.

The results from the present investigation showed 1) wide variability in nocturnal GH secretion before medication; 2) no correlation between nocturnal GH concentration and height, age, bone age, L‐dopa provocative test, or Tanner staging; and 3) no consistent effect on GH release after mazindol, cyproheptadine therapy, or combined therapy.
A case of cardio‐facio‐cutaneous syndrome
Authors: Mucklow E. S.
Published: June 2005

A 6‐yr‐old girl is described who presented with failure to thrive at age 3 months and was found to have mental retardation, growth retardation, disproportionately large head, distinctive face, abnormal hair, eczema, heart defect, splenomegaly, and multiple hemangiomata. She is thought to have the cardio‐facio‐cutaneous syndrome and to be the first such case identified in Britain.
Dandy‐Walker malformation with postaxial polydactyly: A new syndrome?
Authors: Pierquin G. , Deroover J. , Levi S. , Masson T. , Hayez‐Delatte F. , Van Regemorter N.
Published: June 2005

We report on two sibs with Dandy‐Walker malformation and tetramelic postaxial polydactyly. We conclude that this is a new autosomal recessive syndrome.
Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3)
Authors: Ishikiriyama Satoshi , Tonoki Hidefumi , Shibuya Yoshitaka , Chin Shinki , Harada Naoki , Abe Kyohko , Niikawa Norio
Published: June 2005

We report on a child with Waardenburg syndrome type I and a paracentric inversion of chromosome 2. This 20‐month‐old boy has dystopia canthorum, sensorineural deafness, heterochromia iridis, partially albinotic ocular fundi, and partial leukodermia. He does not have mental retardation or any skeletal abnormalities. Family history was unremarkable. Cytogenetic studies demonstrated that the patient has a paracentric inversion (2)(q35q37.3); his parents have normal chromosomes. These findings suggest that the locus of the gene for Waardenburg syndrome type I may be at 2q35 or 2q37.3.
Autosomal recessive form of whistling face syndrome in sibs
Authors: Dallapiccola Bruno , Giannotti Aldo , Lembo Antonio , Sagui Luigi
Published: June 2005

Two sibs with the whistling face syndrome, born to unaffected parents, are presented. They had the full facial and limb manifestations typical of this disorder, for which there is evidence of autosomal dominant inheritance. The existence of an autosomal recessive form of this syndrome has been suspected previously on the basis of a limited number of observations.

Our study substantiates genetic heterogeneity of this condition and suggests that the autosomal recessive form could be even less rare than is generally considered.
Heterogeneity of X‐linked recessive (Spino)cerebellar ataxia with or without spastic diplegia
Authors: Apak Selçuk , Yüksel Memnune , Özmen Meral , Saka Nurçin , Darendeliler Feyza , Neuhäuser Gerhard
Published: June 2005

Ataxia with spastic diplegia was seen in seven males of a Turkish family, obviously transmitted as an X‐linked recessive trait. The first clinical sign in infancy was nystagmus; ataxia and pyramidal signs were noted at age 2–3 years. Patients were never able to walk. Dysarthria, orthopedic impairment, and mild mental retardation appeared later as the disorder progressed. Death occurred in the 3rd or 4th decade from infectious diseases. The syndrome resembles X‐linked spinocerebellar ataxia and X‐linked spastic paraplegia in some aspects but is different if compared with previously published reports. Laboratory and neurophysiological studies showed no abnormalities. Various aspects of X‐linked ataxia are discussed: genetic heterogeneity is apparent from observations reported.
Duplication of 16q and deletion of 15q
Authors: Nyhan William L. , Mascarello James , Barshop Bruce , Doroski Diane , Hirschhorn Kurt
Published: June 2005

A patient with distal arthrogryposis, congenital dislocations of the hips, a prominent forehead, epicanthal folds, thin lips, and a poorly defined philtrum was found to have a deletion of 15q and a duplication of 16q. Her mother, maternal grandmother, and great grandmother had a balanced t(15q−, 16q+). The gene for adenine phosphoribosyl transferase was assignable to the 16q22 → 16qter area that was duplicated.
Antenatal diagnosis of 45,X/48,XYYY
Authors: Bryke Christine R. , Mahoney Maurice J. , Yang‐Feng Teresa L.
Published: June 2005

A diagnosis of 45,X/48,XYYY was made antenatally. Counseling this case was hampered by the paucity of literature describing the phenotype of patients with this chromosome constitution. The fetus had ambiguous external genitalia, a horseshoe kidney, a cerebral cortical cyst and arachnodactyly.
Genetic diagnosis of the preimplantation embryo
Authors: Buster John E. , Carson Sandra A.
Published: June 2005

Genetic diagnosis and therapy is well established in the antenatal period. The advancement of uterine and in vitro fertilization allow access to the early blastocyst. Simultaneously, laboratory techniques are being miniaturized to be sufficiently sensitive and specific for diagnosis with only a few cells. Thus genetic diagnosis and therapy may be extended from the antenatal patient to the antegravid patient. This article discusses the techniques of uterine lavage and in vitro fertilization as well as the diagnostic possibilities that this early embryonic period offers.
“Vascular Neurofibromatosis” and infantile Gangrene
Authors: Kousseff Boris G. , Gilbert‐Barness Enid F.
Published: June 2005

An 11‐year‐old boy with slowly progressive gangrene caused by vasculopathy similar to that of neurofibromatosis (NF) type 1 (NF I; von Recklinghausen disease [NFvR]) and a newborn girl with idiopathic gangrene with vascular changes resembling those of NFvR prompted the analysis of all 105 propositi with NF (NF I and NF II) evaluated between January 2, 1982, and December 31, 1986, at the genetics clinic of University of South Florida. They were analyzed for renal hypertension, symptomatic ischemia, and known vascular changes. One additional 27‐month‐old boy with NFvR was found to have extensive vascular changes with renal hypertension. The vasculopathy indicated asymmetric over/ undergrowth of cellular and extracellular components of the vascular wall and implied dysregulation of the paracrine growth mechanism. Immunocytochemical studies of affected vessels were done only in the 11‐year‐old boy and showed positive neuron‐specific enolase, S‐100 protein, and glial fibrillary acidic protein (GFAP) reactions indicative of Schwann cell involvement.

The vascular changes in children with NFvR are mostly asymptomatic; however hypertension secondary to renal artery stenosis and/or Moya‐moya disease have been reported infrequently. Our patients with vasculopathies provoked thoughts in regard to the so‐called vascular NF, its place in current NF nomenclature and classification, relationship to fibromuscular dysplasia (FMD), and possible role in infantile gangrene.
Recessive inheritance of a high number of sodium pump sites
Authors: Hasstedt Sandra J. , Wu Lily L. , Kuida Hiroshi , Williams Roger R.
Published: June 2005

The number of sodium pump sites on erythrocytes was measured on 1,847 individuals in 80 Utah kindreds ascertained through probands with cardiovascular disease. Likelihood analysis supported recessive inheritance of high pump number. The major locus explained 14.0% of the variance in pump number; polygenic inheritance explained another 63.4%. Homozygotes for the recessive allele occurred with a frequency of 1.74% and had a mean pump number estimated as 566.0 sites/red blood cell (RBC) versus a mean of 312.2 sites/RBC for the other genotypes. Young individuals with the high pump number genotype were leaner, and older adults with the high pump number genotype were heavier. Diabetes and early hypertension were more prevalent in women with the high pump number genotype. Although not significant, obesity in adults of both sexes and early coronary heart disease in men were more prevalent in individuals with the high pump number genotype.
Occurrence of male phenotype in genotypic females with congenital virilizing adrenal hyperplasia
Authors: Chan‐Cua Sioksoan , Freidenberg Gary , Jones Kenneth Lee
Published: June 2005

We report on two genotypic females with complete masculinization of the external genitalia secondary to congenital adrenal hyperplasia resulting from 21‐hydroxylase deficiency. One patient had the salt‐losing variant, and the other had the simple virilizing or nonsalt‐losing variant. One was evaluated neonatally during an adrenal crisis and misidentified as male; the second was unrecognized. Both were being reared as males when the true genotype was recognized during evaluation for cryptorchidism. The female internal genitalia were subsequently removed and testicular implants placed. These cases demonstrate the need to exclude congenital virilizing adrenal hyperplasia in any phenotypic male infant with bilateral cryptorchidism. When this condition is diagnosed, early and genotypically appropriate sex assignment is important if reproductive function is to be preserved and subsequent emotional and social complications avoided.
Craniofrontonasal dysostosis with deafness and axillary pterygia
Authors: Michels Virginia V. , Derleth Douglas P. , Hoffman Alan D. , Goldston Anne S.
Published: June 2005

Craniofrontonasal dysostosis (CFND) is an inherited disorder previously referred to as craniofrontonasal dysplasia. However, there is no evidence of tissue dysplasia and, therefore, the term dysostosis has been substituted. The disorder is characterized by frontonasal dysostosis, coronal craniostenosis, and the variable presence of other skeletal defects, including short webbed neck, sloping shoulders, polydactyly, syndactyly, and broad first toes. Here we report an affected mother and daughter who also have limited hip abduction. In addition, the mother had an axillary pterygia, congenital footplate fixation of the left ear, and right sensorineural hearing loss; these manifestations have not been reported previously in CFND and expand the phenotype of this syndrome. Both patients had marked restriction of shoulder abduction, and the mother had limited forearm pronation; these manifestations have been reported in only one other patient with CFND. Awareness of the possibility of these abnormalities may allow for early intervention by physical therapy and hearing aides in infants and young children with these manifestations as a component of CFND.
Linkage localization of Börjeson‐Forssman‐Lehmann syndrome
Authors: Mathews Katherine D. , Ardinger Holly H. , Nishimura Darryl Y. , Buetow Kenneth H. , Murray Jeffrey C. , Bartley James A.
Published: June 2005

Börjeson‐Forssman‐Lehmann syndrome (BFLS) is a form of X‐linked mental retardation (XLMR) with characteristic minor physical anomalies. It has no biochemical or cytogenetic markers. Heterozygous females may be entirely normal or may have mild‐to‐moderate manifestations. We studied 41 individuals from one family with BFLS for linkage on the X chromosome. The highest lod scores were 2.32 with DXS10 and 2.24 with DXS51, both at a θ = 0.0. A single recombinant was found between HPRT and BFLS. These results suggest that the BFLS locus is on the distal portion of Xq. Previously reported linkage studies in families with XLMR have not shown linkage with DXS10. This study suggests that one of the several X chromosome loci whose dysfunction is associated with mental retardation is located on distal Xq.
MCA/MR syndrome with oligodactyly and Möbius anomaly in first cousins: New syndrome or familial facial‐limb disruption sequence?
Authors: Journel H. , Roussey M. , Le Marec B.
Published: June 2005

We report on two sibs with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome who have a first cousin with Möbius anomaly. This may represent a new MCA/MR syndrome.
Inheritance and phenotypic expression of a t(7;9)(q36;q34)mat
Authors: Krauss C. M. , Liptak K. J. , Aggarwal A. , Robinson D.
Published: June 2005

We describe a subtle familial chromosome rearrangement which involves 7q36 and 9q34. The clinical manifestations of 3 apparently balanced individuals with presumed identical translocation breakpoints are presented. In addition, the phenotypes of 2 cytogenetically unbalanced sibs in the same nuclear family are compared.
Partial deletion of 14q and partial duplication of 14q in sibs: Testicular mosaicism for t(14q;14q) as a common mechanism
Authors: Masada Christopher T. , Olney Ann Haskins , Fordyce Renee , Sanger Warren G.
Published: June 2005

The propositus and a subsequently born sister presented with multiple congenital anomalies. Chromosome analyses were performed initially on peripheral blood lymphocytes from the propositus and his parents: the propositus was found to have a deletion of chromosome 14 (q32.11‐>qter); the parents' chromosomes were normal. When the sister of the propositus was born, she was determined to have a duplication of an equivalent segment of 14qter. Chromosome studies on the parents' fibroblasts demonstrated no structural abnormality or mosaicism. The parents have an older, phenotypically normal, healthy daughter, which supports mosaicism for intragonadal t(14;14)(q32.11;q32.33) in one parent. Chromosome polymorphism comparisons show that the normal number 14 chromosome in the propositus and his sister was inherited from the mother, thus indicating paternal testicular mosaicism. Clinical findings are compared to those of other reported cases of deletion 14q and duplication 14q.
Prevalence of familial hypercholesterolemia in Johannesburg Jews
Authors: Seftel Harry C. , Baker Sheila G. , Jenkins Trefor , Mendelsohn Dennis
Published: June 2005

The prevalence of heterozygous familial hypercholesterolemia was determined in a representative sample of 403 young Jewish men resident in Johannesburg, South Africa. Preliminary screening by measurement of serum total cholesterol demonstrated that 25 of them had levels ⩾ 7.5 mmol/1 (290 mg/dl). On the basis of subsequent clinical, biochemical, and family studies, 6 men, or about 1 in 67 of the total sample, were considered to be heterozygotes. This very high prevalence, about 7 times greater than that found in other Caucasian populations, is probably related to founder effect. It may help to explain the high frequency of coronary heart disease in Johannesburg Jews.
Microtia and associated anomalies: Statistical analysis
Authors: Kaye Celia I. , Rollnick Beverly R. , Hauck Walter W. , Martin Alice O. , Richtsmeier Joan T. , Nagatoshi Konrad
Published: June 2005

Terms such as oculoauriculovertebral dysplasia, Goldenhar syndrome, and hemifacial microsomia have been used to describe microtia with specific combinations of other craniofacial anomalies. Microtia is also observed with anomalies of postcranial structures. Statistical studies were performed on 297 patients with microtia and other anomalies to identify subgroups of patients representing previously described or new associations. Analysis identified 15 subgroups of patients with specific patterns of anomalies. Log‐linear analyses of cranial and postcranial variables demonstrated a positive association between mandibular hypoplasia and cervical spine fusion, which was, in turn, positively associated with other spine anomalies (P < .02) and other skeletal anomalies (P < .001). Although unilateral microtia was commonly observed with mandibular hypoplasia, mandibular hypoplasia was negatively associated with bilateral microtia. Many of the associated anomalies were of structures not derived from the 1st and 2nd branchial arch neural crest. However, most associated anomalies were of structures derived from migratory cell populations or populations undergoing differentiation prior to migration between the 19th and 24th day post‐fertilization (neural crest, ectodermal placode, mesoderm, surface ectoderm). These findings suggest that many different cell populations may be disturbed in the pathogenesis of microtia in association with other anomalies. The timing of the pathogenetic event may determine the specific pattern of associated anomalies.
Third case of Pfeiffer‐type cardiocranial syndrome
Authors: Stratton Robert F. , Parsons David S.
Published: June 2005

We report on a third child with a newly recognized craniosynostosis syndrome involving the sagittal suture. Additional findings not related to the abnormal head growth include micrognathia with limited mouth opening, tracheobronchial anomalies, congenital heart defects, microphallus, cryptorchidism, and growth and mental retardation.
Tay‐Sachs disease carrier screening: Follow‐up of a case‐finding approach
Authors: Clarke J. T. R. , Skomorowski M. A. , Zuker S.
Published: June 2005

In order to determine the status of Tay‐Sachs disease carrier identification in Toronto, Canada, since a change was made in 1978 from testing in the context of large‐scale community clinics (up to 1,200 individuals tested in 1 day) to a case‐finding approach to screening, a sample of area Jews was surveyed by questionnaire. The results indicated that a trend has developed for individuals at risk to delay testing until pregnancy when carrier detection is technically more difficult and the time available for retesting and organizing prenatal diagnosis is limited. If the trend continues, the full potential of chorionic villus sampling (CVS) for the prenatal diagnosis of the disease will be difficult to realize.
Counseling and decision dilemmas associated with fetal blood sampling
Authors: Ulm Janet E. , Shah Dinesh M. , Dev Vaithilingam G. , Phillips John A.
Published: June 2005

Counseling before fetal blood sampling via cordocentesis is more difficult than that done before amniocentesis because 1) a fetal anomaly has been detected or is very likely, 2) the cordocentesis procedure may have a higher risk than does amniocentesis, and 3) the gestational age is frequently advanced before referral. These factors result in counseling and decision dilemmas that include that 1) the advanced gestational age may preclude the option of termination, 2) fetal prognosis may be poor despite normal cytogenetic results, and 3) the benefit of a diagnosis to provide indications for various delivery options must be weighed against the psychological burden of documenting a chromosome abnormality far in advance of delivery. Thus, counseling before cordocentesis requires engaging the couple in decision making regarding potential management of the pregnancy as a prerequisite to choosing or declining the procedure.
Genetic effects in Brazilian populations due to consanguineous marriages
Authors: Freire‐Maia Newton
Published: June 2005

Estimates of “relative risks” and “attributable risks” are presented for two Brazilian regions with the lowest (F=0.00030) and the highest (F=0.00395) inbreeding levels of the country, and for the whole country (F=0.00088). The abolition of all consanguineous marriages (from second cousins up to and including uncle‐niece/aunt‐nephew marriages) in Brazil would eliminate only about 0.22, 3.05, and 0.65% of the “total damage,” respectively. “Total damage” is defined as including abortions, miscarriages, stillbirths, infant‐Juvenile mortality (up to the age of 20 years), and anomalies in the survivors. The reduction of prenatal damage would be 0.11, 1.46, and 0.31%, and that of postnatal damage would be 0.49, 6.65, and 1.36%, respectively.
Fetal loss rate after chorionic villus sampling and subsequent amniocentesis
Authors: Brandenburg H. , Jahoda M. G. J. , Pijpers L. , Reuss A. , Kleyer W. J. , Wladimiroff J. W.
Published: June 2005

Here we review a group of 82 patients who underwent both chorionic villus sampling (CVS) and amniocentesis in the same pregnancy during the period May 1984–May 1988. A fetal loss rate of 2.5% is documented. This is not essentially different from the sum of fetal loss rates following each of the procedures separately (CVS, 1.9%; amniocentesis, 1.0%) established during the same period.