bluuebunny/crossref_metadata_2025 huggingface dataset:
Monozygotic twins concordant for probable Alzheimer disease and increased platelet membrane fluidity
Authors: Zubenko George S. , Ferrell Robert E. , Reynolds James F.
Published: June 2005

This report describes monozygotic twins who were concordant for probable Alzheimer disease, as defined by currently‐accepted clinical criteria. Monozygosity was established by blood typing. Their ages of symptomatic onset were 57 and 66 yr, and the times from onset to institutionalization were 8 and 2 yr, respectively. These results suggest that age at onset and rate of progression are clinical features that can be affected by random processes or exposure to environmental factors. The platelet membrane fluidity of both twins was abnormally increased, and the respective values were identical within experimental limits. This result is consistent with published data suggesting that increased platelet membrane fluidity is associated with a clinically distinct subtype of Alzheimer disease and that this platelet membrane characteristic may be genetically determined.
Renal agenesis with meningomyelocele and absence of Müllerian structures
Authors: Patel Raj‐Rajendra A. , Bixler David , Fraser F. Clarke
Published: June 2005

A new syndrome is identified in an infant. It demonstrates a unique combination of ectodermal and mesodermal developmental defects.
Marfan Syndrome: Exclusion of genetic linkage to three major collagen genes
Authors: Francomano Clair A. , Streeten Elizabeth A. , Meyers Deborah A. , Pyeritz Reed E. , Optiz John M. , Reynolds James F.
Published: June 2005

The Marfan syndrome is an autosomal dominant connective tissue disorder with pleiotropic manifestations affecting skeletal, ocular and cardiovascular systems. Because the fibrillar collagens are major structural components of connective tissue, the hypothesis has long been set forth that the Marfan syndrome is a disorder of fibrillar collagen. We have investigated this hypothesis by performing linkage studies in 12 multiplex families with the Marfan syndrome, using restriction fragment length polymorphisms (RFLP's) associated with 3 genes encoding chains of fibrillar collagens. The data exclude linkage to all 3 candidate genes in 2 families and at least 1 of the candidates is excluded in 6 additional families. Each candidate was excluded in at least 3 families. In no case was strong evidence in favor of linkage of the Marfan syndrome to any of the 3 genes observed. These data speak against the hypothesis that mutations in one or more of these 3 fibrillar collagens cause the classic Marfan syndrome.
Facial midline defect in the fetal alcohol syndrome. Embryogenetic considerations in two clinical cases
Authors: Neri G. , Sammito V. , Romano C. , Sanfilippo S. , Opitz J. M. , Reynolds James F.
Published: June 2005

We report on two unrelated patients with fetal alcohol syndrome with hypoplasia of the periocular region, resulting in a low and narrow forehead and hypotelorism. Other typical manifestations of the syndrome involving the facial midline are also present. These observations can be added to clinical and experimental evidence from other authors, supporting the concept that the facial anomalies of the fetal alcohol syndrome are the expression of a midline defect originating from the disruption of the ordered development of midline mesoderm cells during early embryogenesis.
Monozygotic turner syndrome twins—correlation of phenotype severity and heart defect
Authors: Lin Angela E. , Garver Kenneth L. , Reynolds James F.
Published: June 2005

We report on monozygotic twins with Turner syndrome (45,X) with discordant phenotypes. One twin had severe neck webbing and extremity edema and died of severe coarctation of the aorta. The other twin had fewer craniofacial anomalies and no congenital heart defect, suggesting a pathogenetic relationship between cardiac abnormality and phenotype severity.
Fine mapping of glycerol kinase deficiency and congenital adrenal hypoplasia within Xp21 on the short arm of the human X chromosome
Authors: Davies K. E. , Patterson M. N. , Kenwrick S. J. , Bell M. V. , Sloan H. R. , Westman J. A. , Elsas L. J. , Mahan J. , Optiz John M. , Reynolds James F.
Published: June 2005

We have studied patients with Duchenne muscular dystrophy (DMD), DMD together with glycerol kinase (GK) deficiency, or DMD together with both GK deficiency and congenital adrenal hypoplasia (AHC). Analysis of deletions in these patients allows the mapping of these mutations in Xp21. The following order is proposed: Xpter – L1 – AHC – GK – DMD – Xcen. One of the boys with DMD, GK, and AHC is shown by pulsed‐field‐gel electrophoresis to have a deletion which has a proximal endpoint at least 500 kb distal from the pERT87 (DXS164) locus.
The Weismann‐Netter syndrome
Authors: Robinow Meinhard , Johnson G. Frank , Optiz John M.
Published: June 2005

The Weismann‐Netter syndrome is a rare, heritable dysplasia of anterior bowing of tibiae and fibulae, often with lateral bowing of femora, short stature, and mild mental retardation. The condition is probably due to a primary metabolic abnormality of bone. The disease process is inactive in the adult. The pathogenesis is unknown. The patient reported here is the only child described in the Anglo‐American literature.
Polyostotic fibrous dysplasia with cranial hyperostosis: New entity or most severe form of polyostotic fibrous dysplasia?
Authors: Viljoen D. L. , Versfeld G. A. , Losken W. , Beighton P. , Optiz John M. , Reynolds James F.
Published: June 2005

Polyostotic fibrous (McCune‐Albright) dysplasia is an uncommon nonhereditable disorder characterized by localized or widespread cystic changes in the skeleton. The limb bones are predominantly affected; craniofacial involvement is rare. We have encountered a severely affected man, with the additional manifestation of massive craniofacial hyperostosis. It is questionable whether this condition is an autonomous entity or represents the end of the spectrum of severity of polyostotic fibrous dysplasia.
Direct method for prenatal diagnosis and carrier detection in Duchenne/Becker muscular dystrophy using the entire dystrophy in cDNA
Authors: Darras Basil T. , Koenig Michel , Kunkel Louis M. , Francke Uta , Optiz John M. , Reynolds James F.
Published: June 2005

DNA sequence polymorphisms (RFLPs) have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne muscular dystropby (DMD) in affected families, but serious limitations and pitfalls are associated with this approach [Darras et al., 1987]. The complementary DNA (cDNA) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients [Koenig et al., 1987]. Two prenatal studies are presented to illustrate how the unambiguous identification of deletion mutations by cDNA probes permits direct DNA‐based diagnoses with high accuracy and in otherwise uninformative families. In a single proband family, DNA marker analysds had determined that the Xp21 chromosomal region present in the affected male was also carried by a male fetus in a oubsequent pregnancy. Analysis of this family's DNA with probes covering the entire 14 kb cDNA revealed a small deletion in the affected male that was not present in the fetus nor in the mother. In the second family the fetus was a female deletion carrier identified by comparing intensities of restriction fragments. Since 1/3 of all DMD patients are thought to result from new mutations and most families have only single affected males, the cloned cDNA probes now available are likely to revolutionize DNA‐based diagnostic studies in this disorder. More reliable, more rapid and less expensive than linkage studies with DNA polymorphisms, this methid will be informative in the more than 50% of DMD/BMD cases that have deletion mutations.
Expanding the spectrum of the Perlman syndrome
Authors: Greenberg Frank , Copeland Karen , Gresik Mary V. , Optiz John M. , Reynolds James F.
Published: June 2005

We report on an infant with manifestations of Perlman syndrome including polyhydramnios, macrosomia, bilateral nephromegaly with nephroblastomatosis, visceromegaly and cryptorchidism. Other findings in this infant not seen in previous patients were diaphragmatic hernia, interrupted aortic arch, hypospadias and polysplenia. This infant meets the diagnostic criteria for Perlman syndrome, suggesting that diaphragmatic hernia and cardiac defects may be additional findings in this disorder.
Further diagnostic thoughts about the elephant man
Authors: Cohen M. Michael , Optiz John M. , Reynolds James F.
Published: June 2005

Further evidence for a diagnosis of the Elephant Man's condition is reviewed. It is known that the Elephant Man had “mocassin” lesions, hyperostoses of the skull, and absence of café‐au‐lait spots, all of which are characteristic of Proteus syndrome. Recently, questions have been raised about his skeletal findings and their relevance to neurofibromatosis. However, other skeletal diagnoses have been entertained, including Maffucci syndrome, Paget's disease of bone, pyarthrosis, and fibrous dysplasia. These diagnostic possibilities are discussed and evaluated critically. It is concluded that the skeletal findings are most consistent with Proteus syndrome and coincidental hip disease secondary to childhood trauma.
Report of two cases of distal deletion of the long arm of chromosome 6
Authors: Stevens Cathy A , Fineman Robert M. , Breg W. Roy , Silken Alan B. , Optiz John M. , Reynolds James F.
Published: June 2005

We report on two patients with distal deletions of 6q. In one case a de novo translocation between chromosomes 6 and 7 resulted in del(6q25→6qter). The other case had a de novo deletion, also from 6q25 to 6qter. There have been eight previous reports of distal deletions of 6q. These patients have developmental retardation, microcephaly, craniofacial anomalies, various types of congenital heart defects, and anomalies of hands and feet. The facial similarities of our two patients and those in six published photographs are subtle and may represent an emerging phenotype.
Ethics and medical genetics in the United States. A national survey
Authors: Wertz Dorothy C. , Fletcher John C. , Reilly Philip
Published: June 2005

The approaches of 295 medical geneticists in the United States to 14 clinical problems and 3 screening situations that required a moral choice aresummarized. These data are part of a survey of 682 geneticists in 19 nations. Of 490 U.S. geneticists asked to participate, 295 (60%) returned anonymous detailed questionnaires. There was strong (> 75%) consensus that preserving the mother's confidentiality overrides disclosure of true paternity; that conflicting test results, new/controversial interpretations of results, and ambiguous/artifactual results should be disclosed; that artificial insemination by donor, adoption, taking chances, contraception, sterilization, and in‐vitro fertilization with a donor egg should be presented as reproductive options to carriers of disorders not diagnosable prenatally; that prenatal diagnosis should be performed for patients who refuse abortion and for maternal anxiety in the absence of medical indications; that screening in the workplace should be voluntary. There was no consensus about disclosure of a diagnosis of Huntington disease or hemophilia A to relatives at risk, against the patient's wishes, or about disclosure of parental translocations. Geneticists in the U.S. differed from 18 other nations in presenting surrogate motherhood as an option (67%); willingness to perform prenatal diagnosis for sex selection or refer (62%); and disclosure of XY genotype in a female (62%). Men were more likely than women to say that they would give directive counseling. Women were more likely than men to say that they would perform prenatal diagnosis for maternal anxiety or for sex selection.
Cryptomicrotia and short, stubby fingers with excess fingertip arch patterns in a mother and son
Authors: Tonoki Hidefumi , Ohura Takehiko , Niikawa Norio , Optiz John M. , Reynolds James F.
Published: June 2005

We describe a malformation syndrome of bilateral cryptomicrotia, brachytelomesophalangy, hypoplastic toe nails, and excess fingertip arch patterns in a chrormosomally and mentally normal mother and son. Familial occurrence of this malformation complex has not been described previously and the manifestations of the patients do not correspond to those of any known malformation syndromes. The disorder in this family may be attributable to the pleiotropic effect of an autosomal or an X‐linked dominant gene.
Variant of atelosteogenesis? Report of a 20‐week fetus
Authors: Herzberg Arlene J. , Effmann Eric L. , Bradford William D. , Optiz John M. , Reynolds James F.
Published: June 2005

We report on a 20‐week fetus with manifestations similar, but not identical, to those of atelosteogenesis. The present fetus had rhizomelic micromelia with absence of ossification in the humerus, radius, ulna, and cervical and upper thoracic vertebral bodies; coronal clefts in the ossified thoracic vertebral bodies; and talipes equinovarus. The physes were relatively normal on histologic examination.
Maternal serum hexosaminidase A in pregnancy: Effects of gestational age and fetal genotype
Authors: Ben‐Yoseph Yoav , Pack Beverley A. , Thomas Pamela M. , Nadler Henry L. , Kaback Michael M. , Optiz John M. , Reynolds James F.
Published: June 2005

The diagnostic usefulness of sulfated fluorogenic substrates in carrier detection of Tay‐Sachs disease in serum during pregnancy was assessed by testing coded samples. Gradual increase in serum hexosaminidase activities toward these substrates was observed throughout pregnancy in both carrier and non‐carriers of the Tay‐Sachs gene, but absolute discrimination between the 2 genotypes could not be achieved even when values were compared within the same gestational age. Examination of isolated isozyme fractions with the sulfated substrates showed that the increased activities during pregnancy were due to a genuine increase in hexosaminidase A and not associated with the elevation of hexosaminidase I (or P), which was evident only with unsulfated substrates. The extent of the increase was influenced by the genotype of the fetus as indicated by higher values in pregnant carriers who carried non‐carrier fetuses. We conclude that determination of serum hexosaminidase A during pregnancy by sulfated fluorogenic substrates may have a prenatal diagnostic value when used in obligate heterozygotes for Tay‐Sachs disease, but is unreliable for screening purposes.
Absence of fibula and ulna with oligodactyly, contractures, right‐angle bowing of femora, abnormal facial morphology, cleft lip/palate and brain malformation in two sibs: A possible new lethal syndrome
Authors: Pfeiffer R. A. , Stöss H. , Voight H. J. , Wündisch G. F. , Optiz John M. , Reynolds James F.
Published: June 2005

Absence of fibulae, and unilateral absence of ulna, associated with lateral oligodactyly, and rectangular bowing of the femora are the prominent features of a lethal syndrome studied in two children of related parents. Other malformations are cleft lip and palate and posterior midline abnormalities of the brain. One similar though not identical MCA‐syndrome was reported. The literature is reviewed with respect to ulno‐fibular malformations.
Neurofibromatosis with fully expressed Noonan syndrome
Authors: Abuelo Dianne N. , Meryash David L. , Optiz John M. , Reynolds James F.
Published: June 2005

We present an 18‐year‐old man with neurofibromatosis (NF) and classic manifestations of the Noonan syndrome (NS), including the cardiac findings. His father also has neurofibromatosis but only some of the characteristics of Noonan syndrome. This case lends further support to the notion that the neurofibromatosis‐Noonan syndrome (NF‐NS) is a discrete entity and demonstrates that the NF‐NS can be inherited, with variable expression of the Noonan phenotype within a family.
Aortic hypoplasia and cardiac valvular abnormalities in a boy with fragile X syndrome
Authors: Waldstein Gail , Hagerman Randi
Published: June 2005

An 18‐year‐old mentally retarded male with the Martin‐Bell syndrome was fragile X positive. He died suddenly with viral pneumonia and myocarditis. At autopsy, generalized tubular hypoplasia of the aorta and a mild coarctation were discovered. The base of the mitral and tricuspid valves showed striking aberrations in elastin distribution and structure by light microscopy. Local collagen alterations were also noted. Comparable changes were seen in the skin elastin as well as a severe depletion of acid mucopolysaccharides. These changes suggest a structural disruption underlying the clinical connective tissue problems in some patients with the fragile X syndrome.
Cognitive profiles of boys with the fragile X syndrome
Authors: Kemper Melinda B. , Hagerman Randi J. , Altshul‐Stark Debra
Published: June 2005

Testing 20 boys with the fragile X (or Martin‐Bell) syndrome with the Kaufman Assessment Battery for Children (K‐ABC) showed a consistent pattern of strengths and weaknesses that may be useful in predicting a fragile X positive result from cytogenetic testing. This K‐ABC pattern included 1) Sequential Scale score less than the Simultaneous Scale score; 2) Mental Processing Composite less than the Achievement Scale score; 3) Spatial Memory subtest score less than the Matrix Analogies subtest score; and 4) Arithmetic subtest score less than the mean of the Achievement subtest scores. A comparison group of 20 boys did not demonstrate such a pattern. Testing with the K‐ABC should be considered for boys who present as learning disabled, hyperactive with attentional problems, or mildly retarded. Boys with three or four of the four features of the K‐ABC fragile X pattern should be considered for medical evaluation and cytogenetic testing.
Experience with multiple approaches to the prenatal diagnosis of the fragile X syndrome: Amniotic fluid, chorionic villi, fetal blood and molecular methods
Authors: Shapiro Lawrence R. , Wilmot Patrick L. , Murphy Patricia D. , Breg W. Roy
Published: June 2005

We have had experience with 160 prenatal diagnosis cases for the fragile X syndrome [fra(X)] or Martin‐Bell Syndrome. In 140, amniotic fluid was utilized; 98 had a documented family history of fra(X). The 94 completed cases included 4 no growth; 56 males of which 7 were fra(X)‐positive and 2 false‐negative; 38 females of which 5 were fra(X) positive. There was no fra(X) positive result when a family history of mental retardation was not documented as fra(X). Molecular methods (RFLPs) were utilized in 10 amniotic fluid and 5 chorionic villus specimens (CVS). Percutaneous umbilical blood sampling was used in 2 negative cases and 1 fra(X) positive case because of timing, tissue culture failure or confirmation of another method. CVS were received in 13 cases, and RFLPs were utilized in 5 of the CVS cases. There was no positive fra(X) CVS chromosome result in males, 1 positive result in a female, but 2 false negatives were detected by RFLPs.
Folic acid treatment of fragile X males: A further study
Authors: Fisch Gene S. , Cohen Ira L. , Gross Anne C. , Jenkins Valerie , Jenkins Edmund C. , Brown W. T.
Published: June 2005

Investigations of the effect of high dose folic acid treatment of fragile X syndrome in males has produced mixed results. However, no study had examined the possible drug effects of folic acid on non‐fragile X control males. Therefore, we examined the effect of folic acid on fragile X males using non‐fragile X control males. Subjects were assigned randomly to an ABA or BAB design. Duration of either folic acid or placebo condition was 4 months. Folic acid or placebo was given in a double‐blind fashion. At the end of each condition, the subjects' behavior was assessed.

At the end of the study, parents were asked to complete a questionnaire. Using parents' responses, we examined 22 items on the Autistic Descriptors Checklist and two subscales from the Vineland Adaptive Behavior Scale which corresponded to areas of behavior parents' noted to have shown improvement. We did not find significant differences between fragile X males and control males, within subjects, nor across folic acid and placebo conditions.

Thus, our follow‐up study confirms and extends our original findings, as well as those of other researchers: namely, that no dramatic changes in behavior result from high dose folic acid. Moreover, subtle improvements observed in earlier investigations were not confirmed.
Inactivation pattern of the fragile X in heterozygous carriers
Authors: Fryns Jean‐Pierre , Berghe Herman Van Den
Published: June 2005

In this report we present new data on BrdU‐inactivation studies in lymphocytes of five heterozygotes.

The present data confirm our previous findings that the prediction of the mental status of female heterozygote carriers cannot be based on the X‐inactivation pattern. The general tendency to carry the fragile site on the active X is confirmed and the results of previous studies and hypotheses are reviewed.
Fragile (X) expression, age and the degree of intellectual handicap in the male
Authors: Turner Gillian , Partington Michael W.
Published: June 2005

The proportion of cells expressing the fra(X) was compared to the guardian's opinion of who was the “brighter” in 31 sibships of 2 or more affected males. Six fra(X) positive males in the normal workforce were compared in a similar way to other affected relatives. A correlation was found between lower values of expression and “brightness” by the Wilcoxson signed rank test (<0.01, 2‐tail). A decline in fra(X) expression occurs with age. Some apparently normal non‐expressing transmitting males may be accounted for by these findings.
Multipoint linkage of 9 anonymous probes to HPRT, factor 9, and fragile X
Authors: Brown W. Ted , Ye Wu , Gross Anne C. , Chan Colin B. , Dobkin Carl S. , Jenkins Edmund C.
Published: June 2005

We have analyzed the segregation of restriction fragment length polymorphisms (RFLPs) associated with 9 anonymous probes detecting loci DXS10, DXS15, DXS19, DXS37, DXS51, DXS52, DXS98, DXS99, and DXS100 and probes for HPRT and F9 in a set of 40 families segregating fragile X (fra(X)). Using two‐point and multipoint analysis, we have established their relative genetic locations. The results indicate that DXS99 and DXS10, unlike previous reports, are not tightly linked to F9. A new locus was found to map within the F9 ‐ fra(X) region. DXS98 showed 6% recombination with fra(X) and appeared to be the closest locus to fra(X). These results will be useful for mapping the relative position of newly defined X probes in this region and for future genetic studies of families with fra(X), hemophilia B, or Lesch‐Nyhan mutations.
Pulsed‐field gel mapping studies in the vicinity of the fragile site at Xq27.3
Authors: Patterson M. , Bell M. , Schwartz C. , Davies K.
Published: June 2005

Physical mapping strategies are being employed for an analysis of the fragile X site region. Deletion breakpoints which may be close to the fragile site appear to be at a distance of at least several hundred kb from the nearest DNA probes. Further evidence is found for physical linkage between St14 (DXS52), DX13 (DXS15) and MN12 (DXS33). The data indicate differences in CG content and/or methylation levels between the distal and proximal sides of the fragile site.
Investigation of the twinning rate in families with the fragile X syndrome
Authors: Sherman S. L. , Turner G. , Sheffield L. , Laing S. , Robinson H.
Published: June 2005

An excess of twins in families with the Martin‐Bell or fra(X) syndrome was noted previously in one family study [Fryns, 1986]. We tried to confirm this observation in a second large sample of families from a different population. We calculated the number of twin births among the total number of live births of known obligate carriers found in fra(X) families ascertained in New South Wales, Australia. We only included births of known sex and excluded triplets. There were 5 male pairs, 3 female pairs and 9 unlike sex pairs of twins born among 752 live births. Thus the twining rate was 1/44 per live birth. We compared this rate to that found in two different types of individuals: 1) the rate of 1/96 which was obtained from the 1985 vital statistics for New South Wales, and 2) the rate 1/75 obtained from a sample of live births of obligate carriers with hemophilia A. The increase in twinning among heterozygotes with the fra(X) was highly significant when compared to the census data (p<0.001). However, it was not significantly different from that in the hemophilia data (p<0.05) which were collected in the same way as in the fra(X) families.
Fragile X syndrome: Incidence, clinical and cytogenetic findings in the black and white populations of South Carolina
Authors: Schwartz C. E. , Phelan M. C. , Pulliam L. H. , Wilkes G. , Vanner L. V. , Albiez K. L. , Potts W. A. , Rogers R. C. , Schroer R. J. , Saul R. A. , Prouty L. A. , Dean J. H. , Taylor H. A. , Stevenson R. E.
Published: June 2005

Individuals in South Carolina with the Fragile X [ fra(X) ] or Martin‐Bell syndrome have been ascertained by referral for evaluation of facial abnormalities, macroorchidism or mental deficit; by screening patients in residential and day programs for the mentally retarded; and by family follow up after an index case has been identified. Between 1982 and 1987, 100 positive fra(X) males were diagnosed. Of these, 35 were residents of residential facilities for the mentally retarded representing 2.5% of the population of institutionalized males. Another 23 were found in community day programs for the mentally retarded. Of these 58 cases, 28 (48%) were ascertained by screening for the craniofacial characteristics of the Martin‐Bell syndrome, namely long face, midface hypoplasia, prominent forehead, large mandible and large simple pinnae. Although this screening procedure proved to be productive, it was found that the craniofacial traits of long face, midface hypoplasia, large jaw and simple pinnae were found less frequently in black fra(X) positive males and in prepubertal boys of both races.
The fragile X in sicily: An epidemiological survey
Authors: Neri G. , Sanfilippo S. , Pavone L. , Mollica F. , Barberi I. , Giuffre L. , Romano C. , Mattina T. , Cammarata M. , Ragusa M. G. , Sammito V. , Ventimiglia G. , Musumeci S. A.
Published: June 2005

We have studied a group of 349 institutionalized propositi with mental retardation, and found 12 fra(X)‐positive cases among 155 males (7.7%) and 8 fra(X)‐positive cases among 194 females (4.1%). The males had characteristic manifestations of the Martin‐Bell syndrome. Another 7 males, who were initially considered “borderline”, having expression of fra(X) < 4% and a non‐characteristic phenotype, were eventually considered negative.

Among 5,624 patients (2,764 males and 2,860 females) that were admitted to the Pediatric Department of the University of Catania during the period July 1986 ‐ June 1987, 210 (120 males and 90 females) had mental retardation. Of these, 75 were analyzed for the presence of fra(X) (q27.3); 5 males (0.18% of all males) and 2 females (0.07% of all females) were fra(X)‐positive. The males had the Martin Bell syndrome phenotype.
Fragile X families in a Northern Swedish county ‐ a genealogical study demonstrating apparent paternal transmission from the 18th century
Authors: Holmgren Gösta , Son Blomquist Hans K. , Drugge Ulf , Gustavson Karl‐Henrik
Published: June 2005

Eleven families including 35 cases with fra(X) mental retardation (MR) were traced genealogically using the Research Archives at Umeå University. Seven of the cases were women with fra(X). All of the families originated partly or totally from the county of Västerbotten. It was possible to link 7 of the index families to common ancestors over an 8–11 generation span. The remaining 4 families were not traced to the same ancestors. However, they were linked together pair‐wise over a 7–8 generation span. Transmission of the fra(X) mutation was studied in these families. In the pedigree analyses, priority was given to maternal transmission. In 2 families the fra(X) mutation was transmitted solely through females over 7 or 8 generations respectively. Within 9 families the mutation was transmitted by males in 2–5 generations in order to reach common ancestors.
Pregnancy in women with cerebrotendinous xanthomatosis (CTX): High risk condition for fetus and newborn infant?
Authors: Berginer V. M. , Carmi R. , Salen G. , Opitz John M. , Reynolds James F.
Published: June 2005

Cerebrotendinous xanthomatosis (CTX), is one of the few autosomal recessive progressive storage diseases allowing affected individuals to reproduce. We investigated 38 CTX patients and most of their families. The possibility of a high risk situation for the fetus and/or the apparently healthy newborn infant born to CTX mothers and female carriers of the gene is discussed for genetic counseling purposes and in view of available treatment.
Arachnodactyly and unusual dermatoglyphics: Study of a case
Authors: Krush Anne J. , Schaumann Blanka A. , Youssoufian Hagop , Opitz John M. , Reynolds James F.
Published: June 2005

Clinical and dermatoglyphic findings are reported on a 3–yr old girl with multiple congenital anomalies and unusual dermatoglyphics. The anomalies, including contractural arachnodactyly, rhizomelia (a relative shortening of the proximal segment of the limbs), skin dimples, clinodactyly, disharmonic hand bone maturation, absent, hypoplastic and unusually positioned digital and metacarpophalangeal flexion creases, are not indicative of Marfan syndrome, but it is unclear what this syndrome constitutes. Among the child's most striking dermatoglyphic features, the fingertip patterns (mostly large whorls with extralimital triradii) extend proximally to the middle phalanx and are associated with unusually placed triradii. The furrows between the epidermal ridges are narrower on the volar aspects of the middle and distal phalanges than on the proximal phalanges and palms, resulting in a higher ridge density in the former areas. Dermatoglyphic comparisons between the proposita and her parents are provided. These dermatoglyphic aberrations may indicate the presence of a deleterious agent active during the period of the development of the ridge configurations and of the digital flexion creases.
Achondroplasia with ankylosing spondylitis
Authors: Randolph L. M. , Shohat M. , Miller D. , Lachman R. , Rimoin D. L. , Opitz John M. , Reynolds James F.
Published: June 2005

A 41‐year‐old‐white man with achondroplasia has been followed intermittently since age 27. During this time, he has complained of neck and back pain with limited mobility in both. Other problems have included temporomandibular joint pain, dysuria without apparent urinary tract infection iritis, anemia, and an elevated gamma globulin fraction. Recently he returned to the clinic complaining of rigidity of the entire spine. Radiographs showed complete fusion of the sacroiliac joints and fusion of the cervical vertebral bodies and apophyseal joints, consistent with ankylosing spondylitis. He was found to be HLA B‐27 positive. This case illustrates the importance of considering other diseases whenever atypical orthopedic problems arise in patients with a bone dysplasia.
Cohen syndrome: A connective tissue disorder?
Authors: Méhes Károly , Kosztolányi György , Kardos Maria , Horváth Magdolna , Opitz John M. , Reynolds James F.
Published: June 2005

Mitral valve prolapse and severe gastroesophageal reflux with hiatal hernia were found in a girl aged 2 years, 4 months with Cohen syndrome. The clinical manifestations suggest the presence of a connective tissue disorder in the patient.
The ascertainment sampling problem and estimation of genetic parameters when parental haplotypes are known
Authors: Shute Nereda C. E. , Opitz John M. , Reynolds James F.
Published: June 2005

Comparisons of bias and standard errors of genetic parameter estimates arising from various estimation procedures are made by using contrived genetic data in which parental haplotypes are known in addition to the haplotypes of affected sibs. These comparisons show that knowledge of parental haplotypes can reduce standard errors of genetic parameter estimates by between 10% and 45% as compared to estimates when parental information is not available. The added information does not appear to change the standard errors of ascertainment–assumption–free estimates relative to those from classical methods. This implies that the decision to accept possible bias arising from a classical estimation method or to accept slightly increased standard errors under an ascertainment–assumption–free approach is comparable to that involved when parental haplotypes are unknown.
Insertional translocations: Report of two new families and review of the literature
Authors: Abuelo Dianne N. , Barsel‐Bowers Gail , Richardson Anne , Opitz John M. , Reynolds James F.
Published: June 2005

We describe two families with insertional translocations. In the first, a large family ascertained because of repeated pregnancy loss, the insertional translocation, ins(1;3)(q32;p13pter), was found to be segregating through three generations. In the second family, ascertained through a proposita with congenital malformations, multiple spontaneous abortions also occurred. The father had an insertional translocation, inv 4(p14,q21.1)ins(7,4)(q32;q21.1 q23). These cases illustrate that recurrent fetal wastage may be caused by insertional translocations and in fact may be the only clinical manifestation of this unusual type of chromosome rearrangement.
Meckel syndrome with polysplenia: Case report and review of the literature
Authors: Shen‐Schwarz S. , Dave H. , Opitz John M. , Reynolds James F.
Published: June 2005

A 19‐week gestation female fetus had multiple anomalies suggesting Meckel syndrome with polysplenia. In over 200 reported cases of Meckel syndrome, only 2 similar cases are documented. Both were male infants, one with bilateral left‐sidedness (polysplenia), the other with bilateral right‐sidedness (M‐anisosplenia). Meckel syndrome is a complex MCA (multiple congenital anomaly) syndrome. Thus, the finding of polysplenia is to be interpreted as another such midline anomaly, rather than as a causally independent malformation.
A liveborn infant with tetraploidy
Authors: Lafer C. Z. , Neu R. L. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on an 22‐month‐old white girl with tetraploidy who is growing well, but who is extremely delayed in psychomotor development. When counseling parents it is important to realize that, although quite rare, tetraploid individuals can be born alive and live for at least 22 moths. The implications are also relevant to prenatal diagnosis.
Very superior intelligence in a child with Noonan syndrome
Authors: Finegan Jo‐Anne K. , Hughes Helen E. , Opitz John M. , Reynolds James F.
Published: June 2005

Psychological assessment documents very superior intelligence in a child with Noonan syndrome.
Angular homeostasis II: Pursuit of a moving target in a plane and some implications for cardiac teratology
Authors: Sagawa Y. , Berger K. R. , Trojak J. E. , Brown K. L. , Murphy E. A. , Opitz John M.
Published: June 2005

A model of cardiac ontogenesis is analyzed. It is cast in terms of the geometry of the pursuit of a linearly moving target by the growth of a chain of cells in the same plane, the pursuer, which at each step adjusts its direction of growth towards the current position of the target. The endpoint is the fusion between them, which can occur in 2 modes: either by the leading cell of the pursuer catching up with the target (pursuer‐mediated fusion, or PMF) or by the target running into the preformed side of the pursuer (target‐mediated fusion, or TMF). The causal specifications are the step size, the speed of the pursuer, the speed of the target, the restoration constant, and the initial direction of the pursuer; the outcome variables are the number of steps to fusion and the mode of fusion. The pattern of behavior is complicated, being more‐or‐less regular over large tracts of values, interspersed with abrupt, threshold‐like changes that may generate a dichotomous pattern of inheritance despite a continuous gradation of genetic of other causes. The temporary abolition of the correction process (a change introduced to simulate the pattern of the effect of a teratogen) may delay fusion and suggest how a septum may fail to fuse, the ductus arteriosus to close, or an endocardial cushion to form. But the model also predicts that under certain plausible conditions, the “teratogen” would speed up fusion and hence perhaps offset a genetic predisposition to a congenital defect.
Hyperpigmented lesions of the retinal pigment epithelium in familial adenomatous polyposis
Authors: Baker Richard H. , Heinemann M.‐H. , Miller Helen H. , DeCosse Jerome J. , Opitz John M. , Reynolds James F.
Published: June 2005

Ophthalmic examinations were performed on 56 patients with validated familial adenomatous polyposis (FAP) for hyperpigmented defects of the retinal pigment epithelium. Such lesions were seen bilaterally in 29 patients (52%) and unilaterally in 8 patients (14%). Of the 56 patients, 33 had one or more of the extracolonic expressions associated with Gardner syndrome. We found retinal lesions in 8 patients without any of the expressions of Gardner syndrome. No association was found between Gardner syndrome and the retinal lesions when these patients were compared to patients without any stigmata of Gardner syndrome, nor was any significant association found when each of the expressions was compared individually with the presence of the pigmented retinal lesions. The presence or absence of eye findings were seen to cluster within families. There was no association with sex. Fundus lesions are apparently a variable expression of the FAP gene and are not specifically associated with Gardner syndrome.
Genetic prediction in X‐linked agammaglobulinaemia
Authors: Lau Y. L. , Levinsky R. J. , Malcolm S. , Goodship J. , Winter R. , Pembrey M. , Neri Giovanni , Reynolds James F.
Published: June 2005

S21 (DXS17) and pXG12 (DXS94), two probes linked to the locus of X‐linked agammaglobulinaemia (XLA), were used for genetic prediction in 13 such families. A method of allowing for nonallelic genetic heterogeneity was demonstrated in the calculation of the genetic risks, specifying a certain proportion of unlinked families. We further estimated the impact due to the uncertainty of the proportion of unlinked families on the final genetic risks in each family and this can be taken into account during genetic counseling.
Do some patients with fragile X syndrome have precocious puberty?
Authors: Butler Merlin G. , Najjar Jennifer L. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on an 81½‐year‐old white girl with fra (X) syndrome; she had mental deficiency, hyperactivity, speech disturbances, slightly prominent ears, mild joint laxity and 20% fra (X) expression. Additional findings include idiopathic precocious puberty and a right ovarian cyst. Ovarian cysts have been reported previously in heterozygous females, but to our knowledge idiopathic precocious puberty is a new finding in this syndrome. Whether precocious puberty is a coincidental finding in this patient or a previously unreported manifestation of the fra (X) syndrome is not clear.
Prader‐Willi habitus, osteopenia, and camptodactyly (Urban‐Rogers‐Meyer syndrome): A probable second report
Authors: Pagnan Nina A. B. , Gollop Thomaz Rafael , Opitz John M. , Reynolds James F.
Published: June 2005

Here we describe a 12‐year‐old boy with finger and toe contractures, obesity, mental retardation, osteoporosis, and genital anomalies. This clinical picture was first described by Urban et al. [1979] and has been designated as “Prader‐Willi habitus, osteoporosis, and hand contractures.” To our knowledge, our patient represents the second report of this condition.
Effect of mazindol on growth hormone levels in patients with Duchenne muscular dystrophy
Authors: Zatz Mayana , Rapaport Debora , Vainzof Mariz , de Cassia M. Pavanello Rita , Rocha Jane M. L. , Betti Roberto T. B. , Otto Paulo A. , Opitz John M. , Reynolds James F.
Published: June 2005

Human growth hormone (HGH) inhibition may be beneficial in Duchenne muscular dystrophy (DMD) and slow down the rate of progression of the disease. The purposes of the present investigation were: 1) to assess, through pharmacological stimuli (L‐dopa test), the HGH response in untreated DMD patients, and 2) to evaluate the inhibitory effect of mazindol on HGH levels as a potential treatment for DMD. In 55 DMD patients, HGH levels were measured through the L‐dopa test, and 40 received mazindol. After 1 year, there was wide variability in the individual response to mazindol. An apparent diminution in the mean HGH level was observed in the whole group of patients; this was statistically significant after 3 and 6 months but not after 9 and 12 months of treatment. The results suggest that this drug is not effective for arresting growth or inhibiting HGH secretion for a prolonged period of time.
Pallister‐Killian mosaic syndrome with emphasis on the adult phenotype
Authors: Quarrell Oliver W. J. , Hamill Merryl A. , Hughes Helen E. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 36‐year‐old man with profound mental retardation, “coarse” face, and epilepsy. Recognition of the adult phenotype of the Pallister‐Killian mosaic syndrome was a prerequisite to directing the cytogenetic analysis.
Newly recognized autosomal dominant syndrome of rhizomelic shortness with clavicular defect
Authors: Wallis Colin , Zieff Solly , Goldblatt Jack , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a mother and son with an inherited skeletal disorder of rhizomelic short stature and lateral clavicular defects. This entity has apparently not been reported previously and represents a newly recognized autosomal dominant skeletal dysplasia.
Partial trisomy 9—further delineation of the phenotype
Authors: Smart Ronald D. , Viljoen Denis L. , Fraser Brian , Opitz John M. , Reynolds James F.
Published: June 2005

A patient with partial trisomy 9 (47,XX,+9pter→q22.1) had bilateral cleft lip and cleft palate, enophthalmos, severe micrognathia, small, apparently low‐set ears, and dislocatable knees.

The phenotypic findings are compared with those of other documented cases of total trisomy 9.
Macrosomia and mental retardation: Evidence of autosomal dominant inheritance in four generations
Authors: Mangano L. , Palmeri S. , Dotti M. T. , Moschini F. , Federico A. , Neri Giovanni , Reynolds James F.
Published: June 2005

We describe a large family with 14 persons presenting macrosomia with or without mental retardation in which dominant transmission is evident over 4 generations. A wide range of phenotypic variability was observed, some patients showing macrosomia and mental impairment, others only macrosomia. The cases will be discussed in relationship with other conditions in which the 2 signs may be present, and above all in Sotos sequence.
Congenital diaphragmatic hernia, coarse facies, and acral hypoplasia: Fryns syndrome
Authors: Bamforth J. Stephen , Leonard Claire O. , Chodirker Bernard N. , Chitayat David , Gritter Hilda L. , Evans Jane A. , Keena Beth , Pantzar Tapio , Friedman Jan M. , Hall Judith G. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe five patients with Fryns syndrome. Four presented with diaphragmatic hernia and died in the neonatal period. One did not have diaphragmatic involvement and survived but is severely mentally retarded. All patients had “coarse” faces, microretrognathia, macrostomia, and distal digital hypoplasia. In addition to previously reported traits, our patients had clinical manifestations that have not previously been described, including omphalocele, broad claviles, Hirschsprung “disease,” and anal anomalies. The condition was detected antenatally in three of the cases. The patients include two sib pairs, further supporting autosomal recessive inheritance.
The genetics of Crohn disease: Complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives
Authors: Küster Wolfgang , Pascoe Leigh , Purrmann Jochen , Funk Sabine , Majewski Frank , Opitz John M. , Reynolds James F.
Published: June 2005

We have analysed the pedigrees of 265 probands with Crohn disease, collected from a specialty clinic at the University of Düsseldorf. Complex segregation analysis suggests the presence of a recessive gene with incomplete penetrance for susceptibility to the disease with no residual causes of family resemblance. However, a proportion of the isolated cases are probably due to phenocopies, this proportion being greatest among cases with an advanced age of onset.
Aplasia of pectoralis major muscle and renal anomalies
Authors: Hegde Hardally R. , Leung Alexander K. C. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe two patients with aplasia of the pectoralis major muscle and renal anomalies. We think such an association, which has been reported previously, represents a new congenital malformation, probably not a syndrome but an acro‐pectoro‐renal field defect. We recommend renal ultrasonography be done on all children with aplasia of the pectoralis major.
Tricho‐rhino‐phalangeal syndrome type I with severe mental retardation due to interstitial deletion of 8q23.3–24.13
Authors: Yamamoto Yoshifumi , Oguro Noriko , Miyao Masutomo , Yanagisawa Masayoshi , Opitz John M. , Reynolds James F.
Published: June 2005

Here we report on a 13‐year‐old boy who had an interstitial deletion of the long arm of chromosome 8 [46,XY,del(8)(pter→q23.3::q24.13→qter)]. He had the facial features of the tricho‐rhino‐phalangeal (TRP) syndrome and severe mental retardation, but lacked multiple exostoses. This is the first report with such a peculiar combination of abnormalities and interstitial deletion of 8q.
Neu‐Laxova syndrome: Pathological, radiological, and prenatal findings in a stillborn female
Authors: Russo Rosa , D'Armiento Maria , Martinelli Pasquale , Ventruto Valerio , Neri Giovanni , Reynolds James F.
Published: June 2005

We describe a case of Neu‐Laxova syndrome in a stillborn female. She was born at 41 weeks of gestation to consanguineous Italian parents, who had had 2 previous stillborn offspring. Pathological, radiological, and prenatal studies are reported.
Growth hormone deficiency, Wormian bones, dextrocardia, brachycamptodactyly, and other midline defects
Authors: Stratton Robert F. , Parker Mark W. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 17‐month‐old boy with Wormian bones, short stature, growth hormone deficiency, developmental delay, brachycamptodactyly, dextrocardia, cryptorchidism, midshaft hypospadias, hypoplastic left kidney, and imperforate anus. This unique combination of abnormalities has not been reported previously.
Dystrophin immunocytochemistry in muscle culture: Detection of a carrier of Duchenne muscular dystrophy
Authors: Miranda Af , Francke U , Bonilla E , Martucci G , Schmidt B , Salviati G , Rubin M.
Published: June 2005

Dystrophin is the gene product which is affected in Duchenne muscular dystrophy(DMD). We studied differentiating clonal muscle cultures derived from normal muscle and from the mother of a DMD patient by immunocytochemistry, using anti‐dystrophin antibody. While clonal cultures derived from normal muscle expressed dystrophin in all myotubes, two populations of myogenic cells could be demonstrated in muscle from this possible DMD carrier; in 13 clones the myotubes expressed dystrophin and in 7 clones dystrophin was undetectable. No DNA deletion, duplication or rearrangement was detected by Southern blot analysis of DNA from this family using cDNA probes. Thus, immunocytochemical analysis of clonal muscle cultures may be a useful method to determine whether mothers of DMD patients are carriers of the DMD mutation, especially in the absence of demonstrable gene defects.