bluuebunny/crossref_metadata_2025 huggingface dataset:
Rumination and vomiting in Prader‐Willi syndrome
Authors: Alexander Randell C. , Greenswag Louise R. , Nowak Arthur J. , Opitz John M. , Reynolds James F. , Ledbetter David H.
Published: June 2005

Inability to vomit has been cited as characteristic of Prader‐Willi syndrome (PWS). Although post‐prandial vomiting after gastric by‐pass surgery has been reported, neither vomiting under “typical” circumstances or rumination have been described. Prompted by the discovery of several cases of vomiting and rumination, a questionnaire was sent to members of the PWS Association. Approximately 36% (113/313) of affected individuals reportedly experienced at least one episode of vomiting. Induced vomiting was unsuccessful in 9 of 14 cases in whom results were known. However, no complications of Ipecac were reported. We suggest that there is an alteration in the physiologic set‐point at which vomiting occurs, leading to a decreased propensity to vomit. Liberal and strict definitions of rumination yielded 15.7% and 10.2% positive responses, respectively. Rumination was associated with a history of vomiting. Enamel deterioration consistent with rumination has been observed, and such changes should be looked for in all PWS children. In several instances, rumination was found to decrease when very strict weight control was lessened. Certain individuals may ruminate under too strict a weight control program, and weight control goals should be evaluated to achieve a reasonable compromise between ideal weight and obesity. Vomiting and rumination do not rule out the diagnosis of PWS.
Social skills training of Prader‐Willi staff
Authors: Mitchell William , Cook Kaye V. , Opitz John M. , Reynolds James F. , Ledbetter David H.
Published: June 2005

Over the past 30 years, research interest in PWS has focused on questions related to the identification of syndrome features, determination of etiology and incidence, and effectiveness of both medical and nutritional management strategies. Residential and day treatment facilities have emphasized control of food and of inappropriate behaviors. The present training program developed techniques and materials to encourage positive behaviors and minimize inappropriate behaviors, supplementing earlier techniques. Activities from social skills training curricula were adapted to the needs of PWS persons. Training sessions were held with staff in residential settings to field test the techniques. This paper summarizes the training program and describes effective techniques and materials.
Duchenne muscular dystrophy: Comparison among different racial groups
Authors: Bortolini Eliete Rabbi , Zatz Mayana , Opitz John M. , Reynolds James F.
Published: June 2005

We have compared 232 patients with Duchenne muscular dystrophy belonging to three racial groups: caucasoids, negroids, and mongoloids. Clinical evolution, serum creatine‐kinase, and pyruvate‐kinase levels were analysed in the three groups.

The results of this investigation show that the clinical evolution did not differ significantly among these three racial groups. For serum enzyme activities a statistically significant difference was found only for CK between negroids and mongoloids.
Parental perceptions of the burden of genetic disease
Authors: Ekwo Edem E. , Kim Jae‐On , Gosselink Carol A. , Opitz John M. , Reynolds James F.
Published: June 2005

Parents who are carriers of genes that code for genetic disease face a complex decision regarding procreation. To investigate how parents perceive the potential effects of having a child with congenital defects and how such perceptions influence their reproductive decisions, 202 women accepting and 50 women rejecting amniocentesis after genetic counseling were followed in a 3‐year longitudinal study. Using multiple correspondence analysis, we found that perceived burdens associated with hypothetical congenital abnormalities leading to prolonged illness or early death were considered the most serious, those related to physical handicap or facial abnormalities were perceived as least serious, while genetic defects causing mental retardation fell between. The parents were increasingly likely to accept amniocentesis the more they felt they would be unable to cope with the consequences of a genetic disease leading to prolonged illness or mental retardation (R =.23). Overall, the women who accepted amniocentesis were those who perceived the consequences of congenital malformation as most burdensome. The findings suggest that genetic counselors should not only explore parents' attitudes about specific congenital abnormalities, but also their perceptions of how they would cope with the medical and social consequences of the various genetic defects.
Tibial aplasia‐ectrodactyly as variant expression of the Gollop‐Wolfgang complex: Report of a Brazilian family
Authors: Richieri‐Costa A. , Brunoni Decio , Filho José Laredo , Kasinski Silvana , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a consanguineous Brazilian couple whose 2 children had tibial aplasia‐ectrodactyly. Femoral bifurcation was present in one of the affected children. The relationship of tibial aplasia‐ectrodactyly to the Gollop‐Wolfgang complex is discussed. Clinical and genetic aspects of the conditions involving tibial aplasia and femoral bifurcation are discussed.
Dermatoglyphic development on the volar pads of rats with chromosome abnormalities
Authors: Okajima M. , Yosida T. H. , Ikeuchi T. , Opitz John M. , Reynolds James F.
Published: June 2005

Dermatoglyphic abnormalities are often observed in patients with chromosome aberrations, but no similar observations have been made in animals. In the present study, palmar dermatoglyphics were examined in 4 rats with chromosome anomalies. Reciprocal translocations were induced by γ‐irradiation; the animals used were obtained from among offspring with abnormal karyotypes that were derived from the original mutant rats. As the epidermal surface of the volar pad of the rat is flat, dermatoglyphic characteristics were observed on the dermal surface following staining with toluidine blue. Unusual ridge configurations were found in some of them, suggesting that dermatoglyphic development in the rat reflects, to some extent, an abnormal chromosome constitution.
Cord blood study on β‐thalassemia and hemoglobin E
Authors: Pootrakul Sa‐Nga , Muang‐sup Vanna , Fucharoen Suthat , Wasi Prawase , Optiz John M. , Reynolds James F.
Published: June 2005

We describe hematologic data from 18 newborn infants including follow‐up data. Of these, ten were the offspring of patients with β‐thal/Hb E disease and the remainder were infants who were found to have a decrease in red cell osmotic fragility during a random cord blood examination. The results of the cord blood study showed that two infants having normal red cell osmotic fragility with about 2% Hb E + Hb A + Hb F at birth represented Hb E heterozygosity. Eleven babies had slightly decreased red cell osmotic fragility, a mild degree of microcytosis and poikilocytosis, and hemoglobin types of Hb A + Hb F with no elevation of Hb A2 at birth. They subsequently had hematologic findings consistent with the β‐thal heterozygosity. The means of hematological values of cord blood in the β‐thal trait infants appeared to be statistically different from those in the normal infants only with respect to increased red cell count and reduced MCH. One infant was thought to have the β‐thal trait but had a greater degree of thalassemic changes in red cells; subsequently he turned out to have homozygous β‐thalassemia. Four newborn infants with hypochromia and numerous target cells had 4‐7% Hb E + Hb F without Hb A. Follow‐up examination showed two cases of Hb E homozygosity; however, the others, who had obvious microcytosis and poikilocytosis in cord blood, finally developed β‐thal/Hb E disease. Thus, a careful study on red cell osmotic fragility, morphology and starch gel electrophoresis at birth allows detection and diagnosis of β‐ thal heterozygosity, β‐thal homozygosity, Hb E heterozygosity, Hb E homozygosity and double heterozygosity for β‐thal and Hb E.
A syndrome of multiple congenital contractures: Neuropathlogical analysis on five fetal cases
Authors: Herva R. , Conradi N. G. , Kalimo H. , Leisti J. , Sourander P. , Optiz John M. , Reynolds James F.
Published: June 2005

We performed a neuropathological study on 5 fetuses with an autosomal recessive, lethal syndrome of congenital contractures diagnosed by fetal hydrops on ultrasonography. The fetuses showed a typical pattern of malpositioning of hips and knees with occasional pterygia of the neck and elbows. The muscles were hypoplastic and the spinal cords showed severe thinning, most markedly affecting the ventral half. A total loss of axons in the ventral and lateral funiculi, subtotal loss of anterior horn motor neurons with accompanying astrocytosis and astrogliosis, and similar but less severe changes at the brain stem level suggested a degenerative rather than a dysmorphogenetic mechanism. Sensory nuclei and pathways were distinctly less severely affcted, if at all. The findings further delineate this condition as a genetically and patho‐anatomically distinct autosomal recessive syndrome.
Three cases of untreated classical PKU: A report on cataracts and brain calcification
Authors: Kawashima H. , Kawano M. , Masaki A. , Sato T. , Optiz John M. , Reynolds James F.
Published: June 2005

There are only four previous reports of cataracts in untreated classical phenylketonuria (PKU) patients. Brain calcification, which has been known to occur in patients with dihydropteridine reductase (DHPR) deficiency, has been reported, as far as we know, in only one (albeit unusual) case. We report on three patients with untreated classical PKU; all have cataracts and normal serum levels of glucose and galactose. One of the patients (whose endocrinological tests and biochemistry including folate were normal) has bilateral brain calcifications remarkably similar to that seen in DHPR deficiency. To what extent cataracts and brain calcification occur with classical PKU is unknown because of the lack of case reports addressing these symptoms. Our cases combined with previous reports call attention to the fact that they may be frequently overlooked manifestations of classical PKU.
Isolated familial adrenocorticotropin deficiency: Prenatal diagnosis by maternal plasma estriol assay
Authors: Malpuech Georges , Vanlieferinghen Philippe , Dechelotte Pierre , Gaulme Jacqueline , Labbé André , Guiot Florence , Optiz John M. , Reynolds James F.
Published: June 2005

We report on a brother and sister with adrenal insufficiency due to isolated adrenocorticotropin hormone deficiency discovered in the neonatal period. The first‐born, a male infant, died; pathological findings suggested bilateral adrenal hypoplasia transmitted as an autosomal recessive trait. Plasma estriol levels were assayed during the mother's next pregnancy. The prenatal diagnosis allowed immediate and effective management of the second affected child. The supplementary evidence from the endocrine findings, unavailable on her brother, enabled us to make a diagnosis of isolated central ACTH deficiency. As the defect was found in infants of both sexes in the same family, it is in all likelihood transmitted as an autosomal recessive trait. We consider it important for genetic councelling to perform autopsies on all newborn infants whose death has no apparent cause. Maternal plasma estriol assays during pregnancy can help diagnose fetal adrenal insufficiency, whether the defect is central or adrenal.
Verification of the fetal valproate syndrome phenotype
Authors: Ardinger Holly H. , Atkin Joan F. , Blackston R. Dwain , Elsas Louis J. , Clarren Sterling K. , Livingstone Susan , Flannery David B. , Pellock John M. , Harrod Mary Jo , Lammer Edward J. , Majewski Frank , Schinzel Albert , Toriello Helga V. , Hanson James W. , Optiz John M. , Reynolds James F.
Published: June 2005

We have evaluated 19 children who were exposed to valproic acid (VPA) in utero to look for manifestations of a fetal valproate syndrome (FVS), as proposed by Di Liberti et al. [1984]. We found no consistent alterations of pre‐ or postnatal growth with exposure to VPA monotherapy. Postnatal growth deficiency and microcephaly were present however, in two thirds of children exposed to VPA in combination with other anticonvulsants. Developmental delay or neurologic abnormality was found in 71% of those exposed to VPA monotherapy, and in 90% of those exposed to VPA and other anticonvulsants. Craniofacial anomalies, which can be seen with other anticonvulsant exposures, including midface hypoplasia, short nose with a broad and / or flat bridge, epicanthal folds, minor abnormalities of the ear, philtrum or lip, and micrognathia were also found in infants whose mothers used VPA. Prominent metopic ridge and outer orbital ridge deficiency or bifrontal narrowing and certain major anomalies such as tracheomalacia, talipes equinovarus (with intact spine) and lumbosacral meningomyelocele seem to be peculiar to infants with VPA exposure. Other defects such as urogenital anomalies, inguinal or umbilical hernias, and minor digital anomalies that are common to other prenatal anticonvulsant exposures are also occasionally found in those exposed to VPA. Heart defects have been found in infants exposed to nearly every class of anticonvulsant although the types of defects associated with maternal VPA use may be clarified when classified by pathogenetic mechanism. Our findings overall are in agreement with the report of Di Liberti et al. [1984].
Reproductive risks for carriers of complex chromosome rearrangements: Analysis of 25 families
Authors: Gorski Jerome L. , Kistenmacher Mildred L. , Punnett Hope H. , Zackai Elaine H. , Emanuel Beverly S. , Optiz John M. , Reynolds James F.
Published: June 2005

We have determined the empirical reproductive risks for heterozygous carriers of complex chromosome rearrangements (CCRs). CCRs are structural rearrangements inolving at least three chromosomes and three or more chromosomal breakpoints. Pregnancy outcome, the frequency and type of chromosomal imbalance in the offspring, and the localization and distribution of chromosome breakpoints were analyzed in 25 CCR families ascertained by the birth of a malformed child or repeated spontaneous abortions. This study included two newly ascertained familial CCRs and a total of 67 informative pregnancies. Analysis of the data, after correction for ascertainment bias, showed that the incidence of spontaneous abortions in CCR families was 48.3%. Approximately one in ten pregnancies and 18.4% of all live births to CCR carriers resulted in phenotypically abnormal offspring. One‐half of all CCR carrier liveborn offspring were also CCR carriers. There was a 53.7% incidence of an abnormal pregnancy outcome to CCR carriers. We failed to detect any evidence for a non‐random involvement of specific chromosomes in CCRs. However, we did observe a non‐random distribution of specific breakpoints at sites 1q25, 4q13, 6q27, 7p14, 9q12, 11p11, 11p15, 12q21, 13q31, and 18q21.
Congenital heart defect in a patient with deletion of chromosome 7q
Authors: Tiller George E. , Watson Michael S. , Duncan Lyn M. , Dowton S. Bruce , Optiz John M. , Reynolds James F.
Published: June 2005

We describe a premature male infant with a terminal deletion of 7q [del(7) (pter→q34:)]. Manifestations include low birth weight, hypertelorism, bilateral cleft lip and palate, cryptorchidism, and a complex congenital heart defect. The latter consisted of hypoplasia of the main pulmonary artery, absent pulmonary valve, ventricular septal defect, and anomalous right pulmonary artery.

We briefly review the spectrum of heart defects seen with chromosome 7 deletions, and comment on the incidence of this unusual heart lesion.
Impact of first‐trimester chromosome, DNA, and metabolic studies on pregnancies at high genetic risk. Experience with 1,000 cases
Authors: Sachs E. S. , Jahoda M. G. J. , Kleijer W. J. , Pijpers L. , Galjaard H. , Optiz John M. , Reynolds James F.
Published: June 2005

We describe the results and follow‐up of chorionic villus studies in 1,034 pregnancies at risk for chromosome or metabolic disorders. Direct chromosome studies were successful in 99.7% and yielded results within a few days. Fifty pregnancies at risk for an unbalanced translocation, inherited from parents with many small reciprocal translocations, were a good test for the quality of the direct method.

The 101 metabolic studies involving 28 disorders were correct in 99 pregnancies in the first trimester. In two cases a correct diagnosis was obtained by the confirmatory amniocentesis.

DNA studies were carried out in pregnancies of male fetuses at risk for Duchenne muscular dystrophy and a few metabolic disorders.

The abortion rate after chorionic villus sampling was 5.1 % but more than half of the pregnant women were ≥36 years old and have a spontaneous abortion rate of 10% between the 10th and 14th week according to Gustavii [Lancet 1:562, 1984]. Follow‐up studies confirmed results of all chromosome studies after termination when there was fetal cell growth; the outcome of 504 consecutive continuing pregnancies showed no discrepancies of the phenotype after birth.

It was concluded that first‐trimester chorionic villi studies gave reliable results and were increasingly preferred by the patients, while the sampling can be considered a safe procedure based on the currently available data.
Hepatoblastoma, pigmented ocular fundus lesions and jaw lesions in gardner syndrome
Authors: Krush Anne J. , Traboulsi Elias I. , Offerhaus G. Johan A. , Maumenee Irene H. , Yardley John H. , Levin L. Stefan , Optiz John M. , Reynolds James F.
Published: June 2005

Hepatoblastoma is a rare neoplasm of infants and children only recently documented in association with hereditary adenomatous polyposis of the colon [Kingston et al., 1983]. We report four children with hepatoblastoma from four unrelated families with Gardner syndrome (GS). One child, now 19 years old, survived after a resection of a hepatoblastoma in infancy and recently was found to have GS. He has an associated odontoma and pigmented ocular fundus lesions, both of which have been shown to be clinical markers of GS. Many individuals in these four GS families, both affected and at risk, have osteomatous jaw lesions and pigmented ocular fundus lesions.

A search for colonic polyps should be made in families of infants and children with hepatoblastoma. If the child survives, he or she should be monitored for the later appearance of colonic polyps. The finding of jaw lesions and/or pigmented ocular fundus lesions in relatives at risk are indications of the possible presence of the GS gene.
Multiple “marker” chromosomes: A novel cytogenetic finding in a patient with mental retardation and congenital anomalies
Authors: Tozzi C. , Calvieri F. , Alesi L. , Neri G. , Optiz John M. , Reynolds James F.
Published: June 2005

A patient with mental retardation and clinical manifestations suggestive of Noonan syndrome was found to have in her peripheral lymphocytes multiple small accessory marker chromosomes, varying in number from one to five per cell and in size from about half the size of the q arm of a G group chromosome to less than a centromere.

Occasionally, in the more elongated markers, a G‐positive or a C‐positive band could be identified, or the marker had the appearance of a ring. The origin and significance of these marker chromosomes are discussed.
Relation between height and clinical course in Duchenne muscular dystrophy
Authors: Zatz Mayana , Rapaport Debora , Vainzof Mariz , Rocha Jane M. L. , de Cássia M. Pavanello Rita , Colletto Gloria M. D. D. , Peres Clovis A. , Optiz John M. , Reynolds James F.
Published: June 2005

We have evaluated the relation between height and rate of clinical progression in boys with Duchenne muscular dystrophy (DMD). In all. 111 DMD patients with age ranging from 2 to 23 years (mean 8.2 ± 3.4 years) were assessed; of these patients, 92 had their height measured. Clinical course was determined through Vignos scale of functional disability, motor ability, and timed functional tests. All patients had grossly elevated serum creatine‐kinase (CK) and pyruvate‐kinase (PK) levels. When height was adjusted for patients' age, a statistically significant correlation was found between height and clinical course (positive with Vignos scale and negative with motor ability), suggesting that smaller boys have a better clinical course than taller patients of comparable age. These results support our previous hypothesis and suggest that growth inhibition seems to be effective in diminishing the progression of DMD.
The Tel Hashomer camptodactyly syndrome: Report of a new case and review of the literature
Authors: Pagnan Nina Amalia Brancia , Gollop Thomaz Rafael , Lederman Henrique , Optiz John M. , Reynolds James F.
Published: June 2005

We report on a new case of Tel Hashomer camptodactyly syndrome and review the literature. This syndrome is characterized by skeletal dysplasia, muscle hypoplasia, camptodactyly, and abnormal dermatoglyphics. The inheritance is autosomal recessive with probable partial expression in the heterozygote.
A grandpaternally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg‐Welander syndrome
Authors: Wood Stephen , Shukin Robert J. , McGillivray Barbara C. , Ray Peter N. , Worton Ronald G. , Optiz John M. , Reynolds James F.
Published: June 2005

We report on two sisters with a history of muscle weakness and an electromyogram (EMG) diagnosis of Kugelberg‐Welander syndrome (KWS) or juvenile spinal muscular atrophy. A half‐brother to these women was diagnosed to have Duchenne muscular dystrophy (DMD). Using molecular probes, we identified a deletion within Xp2l in this isolated case of DMD. Sequences detected by pXJ1.1 are deleted, while fragments detected by pERT87 are intact. Both of these probes are derived from the DMD locus. We have shown that the affected sisters share with their half‐brother DNA markers that are linked to the DMD gene and inherited from their maternal grandfather. Dosage analysis of Southern blots show monosomy for pXJ1.1, which has allowed us to determine carrier status within this family and to show that the half‐sisters are manifesting DMD carriers.
Identity‐by‐descent analysis of sibship configurations when parental haplotypes can be distinguished
Authors: Shute Nereda C. E. , Optiz John M. , Reynolds James F.
Published: June 2005

Haplotype sharing patterns of sibs identical‐by‐descent are examined following the method of Ethier and Hodge [1985] but taking account of which parent contributes the shared genes. A means of specification of all distinct sibship configurations is considered, along with the corresponding probability of each configuration and the total number of configurations for differing sibship sizes.
Ring chromosome 12
Authors: Park Jonathan P. , Graham John M. , Andrews Patricia A. , Wurster‐Hill Doris H. , Optiz John M. , Reynolds James F.
Published: June 2005

A ring chromosome 12 (p13.3q24.3) was observed in all cells analyzed from skin fibroblasts and the peripheral blood of a 19‐year‐old man initially referred for developmental delay with expressive language deficiency. Other phenotypic anomalies included growth deficiency, multiple café‐au‐lait spots, mild pectus excavatum, glandular hypospadias. left esotropia, clinodactyly of the fifth lingers, and hypothy‐roidism with elevated antithyroid antibodies. The four previously reported cases of r(l2) support the theory of a general ring phenotypc which is manifested independently of the specific autosome involved and which is characterized by growth failure, moderate mental retardation, and lack of other major phenotypic anomalies. Break‐points in all cases of r(12) have been assigned to the telomeric regions, suggesting minimal deletion of chromosome material.
Aspartoacylase deficiency and N‐acetylaspartic aciduria in patients with canavan disease
Authors: Matalon R. , Michals K. , Sebesta D. , Deanching M. , Gashkoff P. , Casanova J. , Optiz John M. , Reynolds James F.
Published: June 2005

An increased amount of N‐acetylaspartic acid was found in urine and plasma of three patients, from two families, with the diagnosis of cerebral spongy degeneration (Canavan disease). Aspartoacylase was assayed in cultured skin fibroblasts from one patient of each family and a profound deficiency of this enzyme was found. Although the function of N‐acetylaspartic acid is not understood, it is known to occur in high concentration in human brain. The finding of a defect int the metabolism of N‐acetylaspartic acid causing progressive spongy degeneration of the brain may lead to a better understanding of the function of this amino acid derivative. The aspartoacylase assay affords a new tool for determining the diagnosis of Canavan disease. Since aspartoacylase activity was present in cultured amniotic cells and chorionic villi, it is likely that the assay for this enzyme can be used for the prenatal diagnosis of Canavan disease.
Wiedemann‐Beckwith syndrome in apparently discordant monozygotic twins
Authors: Olney Ann Haskins , Buehler Bruce A. , Waziri Mary , Optiz John M. , Reynolds James F.
Published: June 2005

We report 3 pairs of monozygotic (MZ) twins, one twin showing typical Wiedemann‐Beckwith syndrome (WBS) with minimal or no expression of the condition in the co‐twin. These cases are documented, and three previously reported MZ twin pairs are reviewed. Phenotypic concordance for this syndrome in MZ twin pairs has not been reported. Many cases of familial occurrence have been published and different modes of inheritance have been postulated. Based on the twin‐twin variability seen in our patients, it seems the most likely mechanism of inheritance is an autosomal dominant mutation with environmental modification of expressivity, or reduced phenotrance.
Prenatal diagnosis of distal arthrogryposis
Authors: Baty Bonnie J. , Cubberley Don , Morris Colleen , Carey John , Reynolds James F.
Published: June 2005

We report the prenatal diagnosis of distal arthrogryposis type I by ultrasound at 18 wk gestation in a family with two other affected members (mother and sister of the fetus). The pregnancy was followed with serial ultrasounds, and the diagnosis was confirmed after birth. The clinical findings in all affected family members are described. A literature survey of prenatally diagnosed cases of multiple joint contractures is presented. These include cases with many different diagnoses. This is the first report of the prenatal diagnosis of distal arthrogryposis type I. It helps to illustrate the variability and prenatal natural history of the condition and the subtlety of the prenatal ultrasound findings.
XK aprosencephaly and anencephaly in sibs
Authors: Townes Philip L. , Reuter Karen , Rosquete Elizabeth E. , Magee B. Dale , Optiz John M. , Reynolds James F.
Published: June 2005

Recent studies have suggested a causal and pathogenetic relationship between holoprosencephaly and anencephaly. In support of the proposed relationship we report a sibship that includes anencephalic male twins and a female infant with a severe form of alobar holoprosencephaly, radial aplasia, and oligodactyly. The upper limb and brain malformations are considered to represent aprosencephaly syndrome. The coexistence of anencephaly and aprosencephaly within a sibship suggests that XK aprosencephaly syndrome may be an autosomal recessive disorder.
Multiple sclerosis. Updated risks for relatives
Authors: Sadovnick Adele D. , Baird Patricia A. , Ward Richard H. , Optiz John M. , Reynolds James F.
Published: June 2005

Two important characteristics of multiple sclerosis (MS) are familial clustering and a variable age of onset. There is increasing evidence for a genetically influenced susceptibility in MS. Because of this, patients and their relatives are increasingly asking about the risk for relatives of developing MS.

In the MS Clinic in Vancouver, genetic histories are taken routinely for all patients and are updated annually. Patients do not attend the clinic specifically to participate in genetic studies, which could result in over‐representation of familial cases.

Data were available for 815 MS index cases and 11,345 of their relatives. Age‐specific MS risks were calculated for first‐, second‐, and third‐degree relatives of probands and are presented in an easy‐reference format. In general, first‐degree relatives of probands have a risk that is 30–50 times greater than the 0.1% risk for the general population.
Cytogenetic analysis of 688 couples experiencing multiple spontaneous abortions
Authors: Castle David , Bernstein Renee , Optiz John M. , Reynolds James F.
Published: June 2005

We report on cytogenetic analysis of 688 couples experiencing two or more first‐and/or second‐trimester abortions (<20 weeks). The overall abnormality rate was 6.83% (47 couples). However, exclusion of those anomalies not generally accepted as being causal in spontaneous abortion leaves an abnormality rate of only 2.33% (16 couples). We discuss the significance of balanced translations, inversions, sex chromosome aneuploidies, and mosaicisms thereof in the causation of multiple abortions.
Optic nerve coloboma associated with renal disease
Authors: Weaver R. Grey , Cashwell L. Frank , Lorentz William , Whiteman David , Geisinger Kim R. , Ball Marshall , Optiz John M. , Reynolds James F.
Published: June 2005

Optic nerve colobomas can occur as sporadic abnormalities, may be inherited as an autosomal dominant defect, occur as part of syndromes, and are rarely associated with cardiac malformations and midline encephaloceles.

Karcher [1979] described a father and son with the “morning glory” optic disc anomaly and renal disease as a new association.

We report on two brothers with optic nerve colobomas associated with renal disease. The ophthalmologic findings and renal histopathology are presented. This second familial occurrence suggests that the association of optic nerve coloboma and renal disease is a newly recognized syndrome.
Hyperlaxity in males with Melnick‐Needles syndrome
Authors: Fryns J. P. , Schinzel A. , Van den Berghe H. , Reynolds James F.
Published: June 2005

Here we report on a boy with Melnick‐Needles syndrome. He presented extreme hyperlaxity of skin and joints, suggesting that this syndrome is another example of a generalized connective tissue disorder.
Parental decision following prenatal diagnosis of fetal chromosome abnormality
Authors: Verp Marion S. , Bombard Allan T. , Simpson Joe Leigh , Elias Sherman , Reynolds James F. , Hall Judith G.
Published: June 2005

In the event of prenatal diagnosis of fetal chromosome abnormality, parents must choose between continuation and termination of the pregnancy. To determine whether parents are capable of understanding differences in severity among aneuploidy syndromes, we examined the outcome chosen for all pregnancies in which a fetal chromosome disorder was diagnosed at Northwestern Memorial Hospital between January, 1977 and June, 1986. Among amniocentesis cases, 88% with autosomal aneuploidy were terminated, but only 41% with sex chromosome abnormalities and none with de novo structural rearrangements were terminated. Among a smaller group of chorionic villus sampling cases, all with abnormal results were terminated. Similar patterns of parental behavior were noted in other prenatal diagnosis units. We conclude that parents do distinguish among, and respond specifically to, fetal chromosome disorders of differing severity, at least in the second trimester of pregnancy. However, parents appear more inclined to terminate all pregnancies with chromosome abnormalities when the diagnosis has been made in the first trimester.
Rett syndrome in monozygotic twins
Authors: Partington M. W. , Optiz John M. , Reynolds James F.
Published: June 2005

The evolution of the Rett syndrome in 29‐year‐old twin girls is presented. Evidence for monozygosity is given together with a brief account of the problems these girls posed to their family in early childhood.
Variable expression of autosomal recessive polycystic kidney disease and congenital hepatic fibrosis within a family
Authors: Kaplan Bernard S. , Kaplan Paige , de Chadarevian Jean‐Pierre , Jequier Sigrid , O'Regan Sean , Russo Pierre , Optiz John M. , Reynolds James F.
Published: June 2005

Blyth and Ockenden [1971] assigned patients with autosomal recessive polycystic kidney disease (ARPCKD) to 4 discrete groups (perinatal, neonatal, infantile, juvenile) on the basis of the age of presentation. They and others speculated that at least 4 genes were responsible for what they considered to be closely related, but different conditions. These views have gained wide but not universal acceptance. Some workers have insisted that the perinatal and neonatal “forms” of ARPCKD differ fundamentally from the juvenile “form.” However, others have proposed that ARPCKD‐CHF (congenital hepatic fibrosis) and CHF‐ARPCKD are manifestations of the same disease with variation of expression in a kindred.

We report on a patient who presented at birth (1979) with ARPCKD and respiratory distress. He died at 18 hr. An older sib presented at 16 yr in 1984. She had no symptoms, but her mother wanted reassurance that the daughter did not have a condition similar to that of the deceased sib. Blood pressure was 120/80 mm Hg and there was hepatosplenomegaly. A diagnosis of renal tubular ectasia and CHF was made by ultrasonography, radiologic studies, and a liver biopsy.

The evidence from families such as this favors the concept that ARPCKD and CHF presenting as Blyth and Ockenden's perinatal form, and CHF and renal tubular ectasia as their juvenile form, are manifestations of the same genetic disorder, and that the different manifestations are more likely variations in expression than the results of different mutant genes.

The manifestations in this family add weight to the growing body of evidence that intrafamilial variability may occur, not only in autosomal dominant conditions, but also in autosomal recessive disorders.
Diagnosis of classical steroid 21‐hydroxylase deficiency using an HLA‐B locus‐specific DNA‐probe
Authors: Killeen Anthony A. , Seelig Steven , Ulstrom Robert A. , Orr Harry T. , Optiz John M. , Reynolds James F.
Published: June 2005

The HLA‐B and steroid 21‐hydroxylase loci are known to be closely linked. Restriction fragment length polymorphisms seen after digestion of genomic DNA with MspI and TaqI with the HLA‐B locus‐specific DNA‐probe, pHLA‐1.1, were examined in 7 nuclear families with classical steroid 21‐hydroxylase deficiency. In each family 2 polymorphic hybridizing bands (corresponding to the 2 HLA‐B genes) were seen. In all families, TaqI‐generated polymorphisms allowed for Identification of children previously shown on clinical and biochemical criteria to be affected by 21‐hydroxylase deficiency from their unaffccted sibs. The results were in complete agreement with the clinical diagnoses. Among the unaffected children, carriers could be distinguished from non‐carriers in all cases by TaqI polymorphisms. MspI‐geqerated polymorphisms allowed for full identification of genotypes in 5 families. In one family, MspI‐generated polymorphisms could be used to identify affected from unaffected children, but could not distinguish between carriers and non‐carriers. In another family, no identification of genotypes was possible by MspI‐generated polymorphisms alone.

The HLA‐B locus‐specific DNA‐probe, pHLA‐1.1, can be used for diagnosis and genotyping of individuals from families with 21‐hydroxylase deficiency. This technique can be used as an alternative to HLA‐serotyping, or in situations where HLA‐serotyping is technically difficult, for example in chorionic villus samples.
Interstitial deletion 13q. Further delineation of the syndrome by clinical and high‐resolution chromosome analysis of five patients
Authors: Tranebjaerg Lisbeth , Nielsen Karen Brøndum , Tommerup Niels , Warburg Mette , Mikkelsen Margareta , Reynolds James F.
Published: June 2005

Five patients with interstitial deletion 13q are reported. High‐resolution chromosome banding established the diagnosis in two cases and stated the exact breakpoints in three remaining cases. All parents had normal chromosomes. An unequal and so far unexplained sex ratio of previously published and present cases was found: M:F = 1:2.75. Moderate to severe growth retardation was prominent in all patients. The patients were followed with psychological tests and growth data for 3–10 years. Mild to moderate mental retardation was present. Considerable phenotypic similarities were found in two patients with del(13)(q21.33 q31.3) and one with del(13)(q14.3q22.3). Repeat ophthalmological examinations showed no evidence of retinoblastoma in a male with del(13)(ql3.1q21.1).

In conclusion, the long‐term study of five patients with interstitial deletion 13q, all evaluated with high‐resolution banding, contributed to a more reliable mental and growth prognosis in such patients.
Decreased developmental stability as assessed by fluctuating asymmetry of morphometric traits in preterm infants
Authors: Livshits G. , Davidi L. , Kobyliansky E. , Ben‐Amitai D. , Levi Y. , Merlob P. , Optiz John M. , Reynolds James F.
Published: June 2005

Fluctuating asymmetry (FA) of 8 morphometric traits was studied in 113 preterm infants (26–36 wk of gestation), 103 term infants (37–41 wk), and their respective parents. With 3 different measures of FA, the highest values were obtained from extremely preterm infants (26–29 wk), and the lowest from the group of term infants. The estimates of FA values among parents, particularly mothers, showed a similar, albeit less pronounced, trend. Multiple regression analysis of individual mean FA values, calculated in infants for the 8 studied bilateral traits, documented a significant inverse correlation with gestational age and with the health status of the infants and their mothers, as well as a positive correlation with the mothers' mean FA values.
Antley‐Bixler syndrome from a prognostic perspective. Report of a case and review of the literature
Authors: Escobar Luis F. , Bixler David , Sadove Michael , Bull Marilyn J. , Reynolds James F.
Published: June 2005

The Antley‐Bixler syndrome (ABS) is characterized by craniosynostosis, radiohumeral synostosis, and femoral bowing. Other findings include a trapezoid‐shaped head, deformed ears, severe midface hypoplasia, choanal atresiaor stenosis, and long bone fractures. Most ABS cases have died in the firstmonths of life from respiratory complications. The poor prognosis in this condition makes counseling difficult and early termination of pregnancy a consideration. The medical and surgical management information presented herecan be used as a guide for counseling parents in the future.

We report on a new patient with ABS who now at age 3 yr, has been followed by the medical staff of Riley Children's Hospital since birth. She has had successful medical and surgical management.

Although the multisynostoses seen in this disorder is undoubtedly related to the soft tissue malformations such as choanal stenosis and midface hypoplasia, the cause remains unknown. The literature is also reviewed in this condition.
Duplication 18p with mild influence on the phenotype
Authors: Johansson Bertil , Mertens Fredrik , Palm Lars , Englesson Irmelin , Kristoffersson Ulf , Optiz John M. , Reynolds James F.
Published: June 2005

Duplication I8p was found in a 12‐year‐old girl whose father carried a balanced translocation involving the same chromosome segment, t(18;21)(p11;p11). Our patient had delayed speech development, mild psychomotor retardation, epilepsy, and minor anomalies, including a low nasal bridge, anti‐mongolian eye slant, low‐set ears, and narrowly arched palate. These findings are compared with eight previously published cases.
IVIC Syndrome. Report of a second family
Authors: Sammito V. , Motta D. , Capodieci G. , Sanfilippo S. , Neri G. , Optiz John M. , Reynolds James F.
Published: June 2005

The IVIC syndrome derives its name from the Institute Venezolano de Investigaciones Cientìficas, where it was described by Arias et al. [Am JMed Genet 6:25–59, 1980]. We report on several individuals in a family with the IVIC syndrome, the second described in the literature. In this family there are 3 affected individuals in 2 generations. This observation shows that the IVIC syndrome is not a private syndrome, and confirms that it is due to an autosomal dominant mutation.
Maternal age‐specific rates for down syndrome: Changes over time
Authors: Baird P. A. , Sadovnick A. D. , Optiz John M. , Reynolds James F.
Published: June 2005

There have been conflicting reports about whether incidence rates at given maternal ages for Down syndrome (DS) are changing over time. British Columbia provides an excellent opportunity to look at this question as there is 1) nearly complete ascertainment of DS livebirths, 2) a relatively large number of annual births, 3) data on a 20‐year time period, 4) data on age‐specific fertility rates over this period, and 5) cytogenetic data on all pregnancies terminated through the provincial prenatal diagnosis program since its inception.

Data on 856 liveborn DS infants over a 20‐year period (1964–1983) were analyzed. Controlling for maternal ages, the data were examined for transient changes in incidence over time and for linear and cyclic trends. No significant (P>0.05) changes in DS incidence were observed over this 20‐year period in any maternal age group.
Early manifestations of the Martin‐Bell syndrome based on a series of both sexes from infancy
Authors: Hockey A , Crowhurst J
Published: June 2005

A small series of male and female fra(X) positive children is reviewed retrospectively clinically and photographically to identify a profile of age‐related manifestations and behavioral traits of predictive value.

This method involves a crossmatch with the cases and trait lists in the POSSUM Data Base. The plan then is to test the sensitivity and specificity in a prospective series. If this proves reliable, a request for a fra(X) cytogenetic analysis could be limited to the clinically screened matching cases, rather than the present costly exercise of testing all undiagnosed intellectually handicapped children.
Fragile X syndrome: Growth, development, and intellectual function
Authors: Prouty Leonard A. , Rogers R. Curtis , Stevenson Roger E. , Dean Jane H. , Palmer Kim K. , Simensen Richard J. , Coston Gale N. , Schwartz Charles E.
Published: June 2005

We collected data on growth, psychomotor development, speech and language development, and intellectual function on a cohort of 100 males with the fragile X chromosome and 95 carrier females. The data include information on prenatal growth (33 males), growth during the preadult years (32 males), psychomotor development during the first 2 years (25 males), speech and language development (15 males and 5 females), and intellectual function (93 males, 33 females, and 10 obligate carriers who were cytogenetically normal). Birth measurements appeared normal when plotted on the Usher/McLean curves of newborn infants (mean head circumference ‐ OFC ‐ at 40th centile, length at 60th centile and weight at 55th centile). Following birth, OFC rose above the 50th percentile and continued above average throughout the preadult years, whereas average length was above average for the first 5 years only and weight did not deviate from the normal mean. Psychomotor development lagged behind the norm from birth with affected males requiring nearly twice as long as expected to sit alone, walk unassisted, and say first words clearly. All males and females studied had significant language delay; all except one male had abnormalities of articulation. All on whom a clear voice sample was obtained had low voice pitch, and 80% had a hoarse or harsh quality of voice. Five males had word repetitions or perseverative speech during the preadult years. The mean IQ of the 93 males studied was 33 and regression analysis demonstrated a decrease in intellectual performance with age. Four fifths of the female carriers who expressed the fra(X) had intell‐ectual performance in the mentally retarded range and showed similar decrease in performance with age. Obligate female carriers who did not express the fra(X) site had normal IQs (IQ 102 ± 13.3).
Case report: Fragile X syndrome and nephrogenic diabetes insipidus
Authors: Suthers G. K. , Turner G. , Mulley J. C.
Published: June 2005

We describe a man with the fra(X) syndrome and nephrogenic diabetes insipidus. The disease loci for both conditions are in the region Xq27.3–q28. This is the first report of the fra(X) syndrome associated with another X‐linked disorder. Analysis of DNA markers suggested that the association in this man was coincidental.
A new syndrome with mental retardation, short stature and an Xq duplication
Authors: Thode A. , Partington M. W. , Yip M‐Y , Chapman C. , Richardson V. F. , Turner G.
Published: June 2005

We describe a new X‐linked syndrome of marked short stature, severe intellectual handicap and an unusual facial appearance. High resolution prometaphase banding showed affected males to have an X chromosome tandem duplication; their karyotypes were designated 46, dup(X)(q13.1–q21.1)Y. In carrier females the abnormal X chromosome was late replicating. To verify the duplication, gene dosage studies were performed using an enzyme assay and DNA techniques. Prenatal diagnosis is available for carrier females using chromosome analysis of amniocytes or chorionic villi.
X‐linked mental retardation associated with psoriasis: A new syndrome?
Authors: Tranebjærg Lisbeth , Svejgaard Arne , Lykkesfeldt Gert
Published: June 2005

Four males, the sons of 2 sisters, apparently have a new syndrome of mental retardation, seizures and psoriasis.

Due to the relationship between the affected males we propose the inheritance to be X‐linked recessive although cosegregation of two separate disorders may be occurring. Psoriasis has never been reported as a monogenic disorder. Results of cytogenetic studies, including fra (X) and high‐resolution prometaphase analysis, were negative. Steroid sulfatase activities of cultured fibroblasts from 2 surviving affected males were normal. The results of HLA typing of all available relatives did not indicate a strong association between the skin disorder and certain HLA antigens. A healthy sister, who may be heterozygous carrier of the mutant X chromosome, decided on termination of 3 successive pregnancies after prenatal male sex determinations. Her fourth pregnancy with a female fetus is ongoing.