bluuebunny/crossref_metadata_2025 huggingface dataset:
Epiphyseal dysplasia, microcephaly, nystagmus, and retinitis pigmentosa
Authors: Lowry R. Brian , Wood Betty J. , Cox Terry A. , Hayden Michael R.
Published: June 2005

In 1975, we reported two brothers with epiphyseal dysplasia, microcephaly, and nystagmus; one of them also had mild mental retardation. Here we present information on the natural history, particularly with respect to the development of a new visual problem, namely, retinitis pigmentosa.
Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher‐Neuhäuser syndrome
Authors: Limber Ellen R. , Bresnick George H. , Lebovitz Ruth M. , Appen Richard E. , Gilbert‐Barness Enid F. , Pauli Richard M.
Published: June 2005

We describe two families (including one previously reported) in which cerebellar or spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy result from abnormal function of an autosomal recessive gene. Review of the literature adds one other family with this disorder. These three examples confirm the existence of this triad as a specific, pleiotropic, single‐gene syndrome. Careful ophthalmologic evaluation of patients with ataxia and hypogonadotropic hypogonadism may identify additional cases.
Chromosome deletion of Xq25 in an individual with X‐linked lymphoproliferative disease
Authors: Wyandt H. E. , Grierson H. L. , Sanger W. G. , Skare J. C. , Milunsky A. , Purtilo D. T.
Published: June 2005

High resolution chromosome analysis was done on lymphoblastoid cell lines, established during the past decade from affected males with X‐linked lymphoproliferative disease (XLP) or from obligate female carriers, from 14 families. One cell line, from a male with XLP, has a partial deletion of band Xq25. The constitutional nature of the deletion is confirmed in chromosome studies of peripheral blood from the affected individual and represents the first such structural defect to be described in this disorder. Cell lines from the remaining 13 families do not have cytogenetically detectable deletions. This observation will facilitate precise localization, cloning and sequencing of the gene causing XLP.
Postaxial acrofacial dysostosis: Report of a Brazilian patient
Authors: Richieri‐Costa A. , Guion‐Almeida M. L.
Published: June 2005

We report on a Brazilian child with postaxial acrofacial dysostosis (AFD)‐type Genée‐Wiedemann. Clinical and genetic aspects of the postaxial acrofacial dysostoses are discussed.
Pectoralis major defect and Poland sequence in second cousins: Extension of the Poland sequence spectrum
Authors: Fraser F. C. , Ronen G. M. , O'Leary E.
Published: June 2005

We report on a patient with congenital absence of the left pectoralis major muscle, whose second cousin had the full Poland sequence. This suggests that isolated pectoralis major muscles defect should be included in the spectrum of anomalies characterized as the Poland sequence, postulated to result from disruption of blood supply in the embryonic subclavian and vertebral arteries, the site and degree of obstruction determining the sites and severity of the resulting anomalies. Very few cases are familial; in these the family pattern is compatible with an autosomal dominant mutant gene with reduced penetrance or delayed mutation.
Case report and delineation of the congenital hypothalamic hamartoblastoma syndrome (Pallister‐Hall syndrome)
Authors: Iafolla Kimberly , Fratkin Jonathan D. , Spiegel Peter K. , Cohen M. Michael , Graham John M.
Published: June 2005

We report one new case of congenital hypothalamic hamartoblastoma syndrome (Pallister‐Hall syndrome) and one case of a diencephalic nodule associated with craniofacial malformations. Based on a review of 11 cases of Pallister‐Hall syndrome documented by pathological examination, two cases presumed by phenotype, three cases of hypothalamic hamartoma with craniofacial anomalies only, and several cases of related interest, we delineate the clinical, neuroradiologic, and neuropathologic manifestations which aid in differential diagnosis. Clinical manifestations in infants with Pallister‐Hall syndrome included postaxial polydactyly with nail dysplasia, short nose with flat nasal bridge, apparently low‐set, posteriorly angulated ears, kidney and lung anomalies, congenital heart defects, imperforate anus, and micropenis with undescended or hypoplastic testes in males. These manifestations were associated with varying degrees of panhypopituitarism and pituitary aplasia. In three cases of hypothalamic hamartoma associated with craniofacial anomalies only, the face resembled that of holoprosencephaly. Other cases of hypothalamic hamartoma have had associated palate or heart defects or presented with precocious puberty. Of the infants with a hypothalamic hamartoblastoma at autopsy, neuropathologic findings were consistent with a primitive neuroectodermal tumor. Surgical tissue from our sole survivor suggested such tumors might mature, and the tumor has not recurred. Neuroradiologic diagnosis may be difficult but should be attempted in infants with these clinical manifestations; due to the need for prompt initiation of appropriate therapy.
Growth and development in thanatophoric dysplasia
Authors: MacDonald Ian M. , Hunter Alasdair G. W. , MacLeod Patrick M. , MacMurray S. Brock
Published: June 2005

Two cases of prolonged survival of thanatophoric dysplasia are presented, in which ventilatory support was initiated in the neonatal period because of respiratory distress. Both patients required a ventriculoperitoneal shunt for hydrocephalus and had decompression of the posterior fossa. The history of each patient has been characterized by profound developmental delay and dramatic growth failure.
Longitudinal IQ changes in fragile X males
Authors: Hagerman Randi J. , Schreiner Rebecca A. , Kemper Melinda B. , Wittenberger Michael D. , Zahn Betsy , Habicht Kristin
Published: June 2005

Previous studies have reported a drop of IQ in males with Martin‐Bell or fragile X syndrome during childhood and adolescence. It is uncertain when and why this drop occurs and whether it affects all fragile X males. We have analyzed longitudinal IQ data on all 24 fragile X males who have been followed for at least 2 years through the Child Development Unit in Denver and who have been evaluated with a Stanford‐Binet Form L‐M assessment. A significant drop in IQ occurred for the group as a whole, but an individual z analysis demonstrated that only 7 of 24 had a significant decline in IQ. Visual inspection demonstrates an initial decline in IQ beginning in middle childhood and continuing through adolescence. We postulate that this drop occurs because of relatively greater weaknesses with abstract reasoning and higher symbolic language skills that are stressed in the cognitive testing of later childhood and adolescence.
Absence of familial association between dementia of Alzheimer type and down syndrome
Authors: Berr C. , Borghi E. , Rethoré M. O. , Lejeune J. , Alperovitch A.
Published: June 2005

The aim of this study was to test whether there is an excess of dementia of Alzheimer type (DAT) cases in Down syndrome (DS) relatives. We conducted a case‐control study in families of DS children with classical trisomy 21. A control group was constituted of families of children referred to the same hospital for benign diseases.

Families of 188 DS children and 185 controls were recruited. We obtained vital statistics on 1,850 (response rate 82%) grandparents and great‐grandparents in the DS group and 1,525 (69%) in the control group. Rates of possible severe dementia were calculated on ancestors over age 60 years with available data on mental function, 1,336 in the DS group and 1,113 in the control group. Rates of possible severe dementia were similar in the two groups: 5.6% (78 cases) in DS and 6.2% (66 cases) in control. Dementia with insidious onset suggestive of DAT was observed in 2% (28 cases) of DS ancestors and 2.6% (28 cases) of control ancestors.

Our results argue against an excess of dementia cases with insidious onset suggestive of DAT in families of children with classical trisomy 21.
Familial Mediterranean fever in Armenians: Autosomal recessive inheritance with high gene frequency
Authors: Rogers David B. , Shohat Mordechai , Petersen Gloria M. , Bickal Joan , Congleton Jane , Schwabe Arthur D. , Rotter Jerome I.
Published: June 2005

Familial Mediterranean fever (FMF) is a recurrent episodic inflammatory disorder of unknown pathogenesis that occurs with high frequency in non‐Ashkenazi Jews and Armenians. However, there are some differences in the clinical manifestations of FMF in these ethnic groups. FMF has been reported to be an autosomal recessive disease in non‐Ashkenazi Jews, with a male/female ratio of 1.7, indicating reduced penetrance in females. However, the inheritance is less clear for Armenians. To resolve this problem, we studied prospectively families of 64 Armenian index cases randomly ascertained at the UCLA FMF clinic. Fifty‐three families containing 176 sibs in addition to the probands were analyzed by genetic segregation analysis (exclusions included: six single‐child families, four families in which one of the parents was also affected, and a family with incomplete information). Upper and lower bounds of the segregation ratio were estimated, and ranged from.10 ± .03 to.18 ± .05 when only definitely affected sibs were classified as affected;.17 ± .04 to.27 ± .05 when considering “possibly affected” sibs as affected; and.19 ± .04 to.30 ± .05 when incomplete penetrance in females was corrected. A value of.25 is the expected segregation ratio for autosomal recessive inheritance, and our data are consistent with this mode of inheritance. We can reject autosomal dominant inheritance, where the expected segregation ratio is.5. Using extended pedigree data, we calculated an FMF gene frequency of 0.073 and a carrier rate of 1/7, which is about four times the frequency in non‐Ashkenazi Jews. The parent‐to‐offspring transmission of FMF reported in Armenians can be explained by its high gene frequency in this ethnic group. We conclude that, despite the clinical differences, FMF is an autosomal recessive disease in all ethnic groups studied to date.
Autism is not associated with the Fragile X syndrome
Authors: Einfeld Stewart , Molony Helen , Hall Wayne
Published: June 2005

We provided a controlled test of the hypothesis that individuals with the Martin‐Bell or Fragile X [fra(x)] syndrome are more autistic than mentally retarded control individuals. A sample of fra(x) individuals was obtained from the register of a clinical genetics unit and compared with mentally retarded control individuals selected from an assessment centre who were individually matched for age, sex, and IQ. A comparison of 45 pairs of fra(x) cases and control individuals on the DSM‐III (R) criteria for autism and two standardized “instruments” for the assessment of autism (ABC and ADC) failed to find a higher prevalence of autism among fra(x) individuals. There was no statistically significant difference between fra(x) individuals and control individuals, and the mean differences on both the ABC and ADC scales were in the direction contrary to the hypothesis. An analysis of the study's statistical power suggested that it is unlikely the investigation failed to detect a large to medium difference between fra(x) individuals and control individuals in autistic behaviour. Subsidiary analyses of case‐control differences showed that two autistic‐like behaviours occurred at a higher rate among fra(x) individuals than other mentally retarded children, namely, gaze avoidance and hand flapping. These abnormalities may have misled clinicians into thinking that autism and fra(x) are associated.
“New” ectodermal dysplasia syndrome with distinctive facial appearance and preaxial polydactyly of feet
Authors: Wilson William G. , Greer Kenneth E. , Martof Andrew B. , McIlhenny Joan , Hatter Dennis L.
Published: June 2005

We describe a 2‐year‐old girl with virtual absence of body and scalp hair, rounded nails, thin dental enamel, preaxial polydactyly of feet, and unusual facial appearance. This combination of findings is not similar to that of any of the previously described ectodermal dysplasia syndromes and may represent a new disorder.
Translocation t(5;11)(q13.1;p13) associated with familial isolated aniridia
Authors: Pettenati Mark J. , Weaver R. Grey , Burton Barbara K.
Published: June 2005

A father and daughter with isolated aniridia were observed to have an apparently balanced, reciprocal translocation involving chromosomes 5 and 11 [t(5;11)(q13.1;p13)]. No other clinical characteristics often associated with the deletion of 11p13 were observed in this family. This finding, in association with 3 other instances of single breaks at 11p13 and aniridia, supports the assignment of AN2 to 11p13.
Three sibs with achalasia and alacrimia: A separate entity different from triple‐A syndrome
Authors: Haverkamp F. , Zerres K. , Rosskamp R.
Published: June 2005

We report on two brothers and one sister with achalasia and alacrimia born to consanguineous unaffected parents. The combination of achalasia and alacrimia may represent an entity different from the triple‐A syndrome in showing normal adrenal function.
Ambiguous genitalia associated with skeletal abnormalities, cutis laxa, craniostenosis, psychomotor retardation, and facial abnormalities (SCARF syndrome)
Authors: Koppe Roswitha , Kaplan Paige , Hunter Alasdair , MacMurray Brock
Published: June 2005

We describe 2 male maternal first cousins, 7 years and 7 months old, with a previously unreported pattern of malformations including lax skin, joint hyperextensibility, umbilical and inguinal herniae, craniosynostosis, pectus carinatum, several abnormally shaped vertebrae, enamel hypoplasia and hypocalcification of the teeth, facial abnormalities and wide webbed neck, ambiguous genitalia, multiple nodular liver tumors, and mild psychomotor retardation. The occurrence of 2 male children related through their mothers suggests the possibility of X‐linked recessive inheritance. It is proposed to call this disorder the SCARF syndrome (skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, retardation, facial abnormalities).
Psychological aspects of genetic counseling: VI. A critical review of the literature dealing with education and reproduction
Authors: Kessler Seymour
Published: June 2005

The post‐1979 literature dealing with the educational and reproductive outcome and process of genetic counseling is reviewed. Despite methodological difficulties, recent publications strongly suggest that genetic counseling is successful in educating counselees about diagnostic and risk information. In general, investigators suggest that there is room for improvement and the factors leading to imperfect recall of information need to be elucidated. Process studies suggest that the educational priorities of counselors and counselees may not always be consistent. The contribution of these inconsistencies to outcome measures needs further study. Also, it appears that differing counseling approaches may be equally effective in achieving educational goals. Studies on the reproductive outcome of genetic counseling show no strong impact of counseling; there appears to be a net increase of desire for more children following counseling. Precounseling reproductive intentions, rather than counseling, were found to be a major factor in determining postcounseling outcome. Process studies suggest that although many counselees say that they were influenced by genetic counseling, it is uncertain what they mean, since for many counselees, reproductive decisions seem to have been made prior to counseling.
Apparent Smith‐Lemli‐Opitz syndrome and Miller‐Dieker syndrome in a family with segregating translocation t(7;17)(q34;p13.1)
Authors: Berry Rebecca , Wilson Harry , Robinson Jeanne , Sandlin Constance , Tyson Wes , Campbell John , Porreco Richard , Manchester David
Published: June 2005

We describe a family in which one male infant presented with Miller‐Dieker syndrome and four male relatives had a phenotype similar to the Smith‐Lemli‐Opitz (SLO) syndrome. High resolution cytogenetic analysis on the child with Miller‐Dieker syndrome showed 46, XY, −17, + der17t(7;17)(q34:p13.1). Paternal chromosomes showed a balanced translocation: 46, XY,t(7;17)(q34:p13.1). The paternal grandmother had a history of multiple miscarriages, and a paternal uncle had two sons who died neonatally. Chromosomes on these children and their father had originally been reported as normal. There was also a paternal cousin to the father of the propositus who had had two sons with similar clinical findings. A diagnosis of SLO syndrome was considered. Image enhancement techniques on previous suboptimal preparations on these four children documented the subtle unbalanced translocation 46, XY, − 7, + der7t(7;17)(q34:p13.1). Subsequent high resolution analysis on one of these four children who was still living confirmed this chromosome constitution. It is postulated that these apparent SLO cases may represent a contiguous gene syndrome in which SLO or a separate entity closely mimicking the syndrome in included.
Apparent Fryns syndrome in a boy with a tandem duplication of 1q24‐31.2
Authors: Clark Robin Dawn , Fenner‐Gonzales Melissa
Published: June 2005

We report on a newborn boy with manifestations of Fryns syndrome who also had a mosaic tandem duplication of chromosome 1q24‐31.2. The child had a diaphragmatic hernia, cleft palate, hypoplastic and absent digits, micrognathia, long philtrum, thin upper lip, and anteverted nose. The baby died at age 5 hours. An autopsy demonstrated absent right middle lobe of the lung, bilateral renal cysts, hypoplastic renal arteries, urethral stricture, hydronephrosis, and aortic coarctation. The brain was abnormal with absent olfactory tracts and cerebral and cerebellar heterotopias.

This is the first report of a chromosome anomaly in a child with Fryns phenotype. It suggests that the gene for Fryns syndrome may be located in the region 1q24‐31.2.
Choroideremia and hypopituitarism: An association
Authors: Menon Ram K. , Ball William S. , Sperling Mark A.
Published: June 2005

Choroideremia is a rare X‐linked, progressive, degenerative disease of the retina and choroid. We describe 2 patients, one a female, with choroideremia documented to have hypopituitarism and neurological abnormalities. We hypothesize that this previously undescribed association results from a degenerative process involving tissues of neural origin, or from contiguous submicroscopic gene deletions in the X chromosome region that define choroideremia and possibly hypopituitarism.
Prenatal detection of a gene for hereditary amyloidosis
Authors: Nichols William C. , Padilla Lillie‐Mae , Benson Merrill D.
Published: June 2005

Autosomal dominant amyloidosis of the Indiana/Swiss type (familial amyloidotic polyneuropathy type II) is a late‐onset disorder characterized by carpal tunnel syndrome, peripheral neuropathy, vitreous opacities, and cardiomyopathy. The genetic basis of the disease is a variant of plasma prealbumin (transthyretin) which has a serine for isoleucine substitution at amino acid 84 of the 127 residue prealbumin molecule. Using the polymerase chain reaction (PCR), we amplified exon 3 of the prealbumin gene in DNA extracted from amniocytes of a fetus at‐risk of carrying the serine‐84 prealbumin gene. By allele‐specific oligonucleotide analysis as well as restriction enzyme analysis of the amplification products it was determined that the fetus was a carrier of the serine‐84 variant gene. This finding was confirmed at birth by Southern blot analysis using DNA obtained from cord blood. This is the first report of the prenatal detection of a gene for hereditary amyloidosis.
New type of autosomal recessive short‐limb dwarfism with absent fibulae, exceptionally short digits, and normal intelligence
Authors: Kohn Gertrude , Veder Max , Schoenfeld Alex , El Shawwa Raghda
Published: June 2005

Short‐limb dwarfism is of heterogeneous origin and has various clinical manifestations. This communication describes a previously apparently unreported type of short‐limb dwarfism in 3 affected sibs. Characteristics of this syndrome are bilateral absence of fibulae and severe abnormalities of all digits.
Macrocephaly, multiple lipomas, and hemangiomata (Bannayan‐Zonana syndrome): Genetic heterogeneity or autosomal dominant locus with at least two different allelic forms?
Authors: Moretti‐Ferreira Danilo , Koiffmann Célia P. , Souza Deise H. , Diament Aron J. , Wajntal Anita
Published: June 2005

We describe a boy with mild manifestations of the Bannayan‐Zonana syndrome (BZS): large scaphocephalic head with marked frontal bossing, hypertrophy on the right side of the body, large and irregular café‐au‐lait spots, and cutaneous telangiectasia on large parts of the body and a cavernous hemangioma on the internal side of the left leg; soft cutaneous masses were present in the left axilla and inner part of the left arm; hypotonia and mild neurologic dysfunction were also present. BZS is reported as an autosomal dominant condition with variable expressivity; analysis of our data and those reported in the literature suggest that the interfamilial variability observed might represent different allelic mutations, or genetic heterogeneity.
Familial hyperinsulinism with nesidioblastosis of the pancreas: Further evidence for autosomal recessive inheritance
Authors: Moreno Luis A. , Turck Dominique , Gottrand Frederic , Fabre Monique , Manouvrier‐Hanu Sylvie , Farriaux Jean‐Pierre
Published: June 2005

We report on a brother and sister with hyperinsulinism and nesidioblastosis of the pancreas. In addition, one brother and one sister who died in the neonatal period were probably affected. The parents of these children were healthy and consanguineous. We think that this is strongly suggestive of autosomal recessive inheritance. Seven other reports of presumed autosomal recessive hyperinsulinism are reviewed. To our knowledge, we report the first case in sibs whose parents were consanguineous. We think that early recognition of the condition is of obvious importance not only for therapy, but also for purposes of genetic counseling.
Familial 5q11.2→q13.3 segmental duplication cosegregating with multiple anomalies, including schizophrenia
Authors: McGillivray Barbara C. , Bassett Anne S. , Langlois Sylvie , Pantzar Tapio , Wood Stephen
Published: June 2005

We report on 2 relatives with a segmental duplication of 5q11.2→13.3. The phenotype is surprisingly limited for the degree of chromosome imbalance, the propositus presenting with schizophrenia. Using RFLP markers, we have shown that the gene for HEXB lies within the duplicated region. We suggest this region as a candidate region for the location of a single major gene which predisposes to schizophrenia and which may be assessed by linkage analysis.
Autosomal recessive Robinow syndrome
Authors: Teebi Ahmad S.
Published: June 2005

Two brothers of normal first‐cousin parents were found to have Robinow syndrome. Their paternal uncle also married a first cousin and had 3 similarly affected children (2 boys, 1 girl). The 2 affected brothers had short stature, mesomelic and acromelic brachymelia, characteristic face with hypertelorism, wide palpebral fissures, midface hypoplasia and large mouth, and hypogenitalism. Parental consanguinity and affected individuals in 2 sibships of common ancestry strongly suggest autosomal recessive inheritance. Similar cases from the literature are briefly reviewed.
Clinical pattern and the genetics of the fetal iodine deficiency disorder (endemic cretinism): Results of a field study in Highland Ecuador
Authors: Held Karsten R. , Cruz Marcelo E. , Moncayo Fausto
Published: June 2005

The clinical manifestations of various degrees of mental retardation, spastic diplegia, and deaf mutism are known as the neurologic type of endemic cretinism (EC), occurring in countries with high goiter endemicity. Maternal iodine deficiency has been established as the major cause in EC, whereas a genetic predisposition has not been well‐documented. Genetic data on 70 families with EC from Highland Ecuador are reported. A segregation analysis of 49 fully classified families yielded an estimate of P=0.245 (var [P]=0.00167). Half‐sibs were all unaffected and no significant birth order effect was observed among 101 probands. The data indicate an autosomal recessive predisposition as a major etiological factor. Because the neurologic type of EC represents a defined section of the spectrum of iodine deficiency disorders (IDD), the term fetal iodine deficiency disorder (FIDD) rather than cretinism is suggested. The clinical findings in 70 patients were used to delineate the minimal diagnostic criteria of FIDD.
Waardenburg syndrome and Hirschsprung disease: Evidence for pleiotropic effects of a single dominant gene
Authors: Badner Judith A. , Chakravarti Aravinda
Published: June 2005

Segregation and linkage analysis was performed on published data on 5 families segregating for Waardenburg syndrome (WS) and Hirschsprung disease (HRSD). Two of these families demonstrated parental consanguinity. On the basis of these families, autosomal recessive inheritance of the combination WS‐HRSD has been postulated. However, a single dominant gene with pleiotropic effects leading to WS and HRSD, with a more severe phenotype in homozygotes, is more plausible. A model of gene action incorporating stochastic effects is compatible with these observations.
Five landmarks in inbreeding studies
Authors: Freire‐Maia Newton
Published: June 2005

A short review is made on papers by Mendel, Wright, Haldane and Moshinsky, Cotterman, Malécot, Morton et al., and Khoury et al. The accompanying paper applies the two epidemiological approaches of this paper to the Brazilian populations.
Mouse major histocompatibility complex (H‐2) and fetal lung development: Implications for human pulmonary maturation
Authors: Hu Ching‐Chum , Jaskoll Tina F. , Minkin Cedric , Melnick Michael
Published: June 2005

Using C57/10Sn (B10, H‐2b) and B10.A/SgSn (B10.A, H‐2a) congenic mice, we measured 1) the level of endogenous pulmonary cor‐ticosterone during mouse development;2) the degree of lung morphological maturation on gestation day 17, with or without corticosteroid treatment; and 3) the maternal influence on normal lung development and fetal response to corticosteroids. The results of our study indicate that there was a progressive increase in the level of endogenous hormone with time in fetal B10 (H‐2b) and B10.A (H‐2a) mice; throughout mid‐ to late gestation, the detectable amount of hormone was almost identical in lungs of both strains. Evaluating the degree of lung maturation by morphometry, B10.A mouse lungs were found to be less mature than B10 mouse lungs. Following corticosteroid treatment on day 12 of gestation, H‐2a lungs were equal to or more mature than H‐2b lungs. We also compared heterozygous mouse lungs from reciprocal crosses (B10. B10.A, b/a and B10.A.B10, a/b). Mice with a maternally derived H‐2a haplotype had less mature lungs than those with a maternally derived H‐2b haplotype, suggesting a maternal effect. When exogenous hormone was administered, all heterozygous mouse lungs increased in maturity regardless of the origin of the H‐2a haplotype. The treated a/b or b/a lungs were more mature than homozygous b/b and less mature than homozygous a/a lungs. We conclude that progressive lung maturation is associated with a gene (s) at or near the H‐2 complex, as is the ability to respond to corticosteroids.
Geleophysic dysplasia
Authors: Wraith James E. , Bankier Agnes , Chow C. W. , Danks David M. , Sardharwalla Imdad B.
Published: June 2005

We describe 2 children with geleophasic dysplasia. Prominent cardiac disease in one of the patients caused death at an early age. The history of consanguinity in one of the families supports autosomal recessive mode of inheritance. Histological and ultrastructural changes suggest that a disturbance in the relations between cell membrane and extracellular matrix may be involved in the pathogenesis.
Review of the development and current status of techniques for monitoring embryonic and fetal development in the first trimester of pregnancy
Authors: Ward Humphry
Published: June 2005

This review is confined to the historical background and development of the 2 principal methods of chorionic villus sampling. The failure rate and incidence of fetal losses are presented for a variety of instruments. Early referral is essential to optimise the use of these techniques.
Direct chromosome preparation and culture using chorionic villi: An evaluation of the two techniques
Authors: Simoni Giuseppe , Terzoli Gianluigi , Rossella Franca
Published: June 2005

We present a comparison between direct chromosome preparation and cell culture for first trimester fetal chromosome study using chorionic villi. The 2 techniques have advantages and disadvantages and are demonstrated to be appropriate for routine diagnostic work.

The combined use of both methods may optimize the quality of the chromosome study and minimize the possibility of false‐positive and false‐negative findings.
Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin
Authors: Barshop Bruce A. , Wolff Jon , Nyhan William L. , Yu Alice , Prodanos Christina , Jones Gilbert , Sweetman Lawrence , Leslie Jack , Holm Jan , Green Ralph , Jacobsen Donald W. , Cooper Bernard A. , Rosenblatt David
Published: June 2005

An infant with deficiency of transcobalamin II (TCII) presented with virtually complete failure to thrive and life‐threatening pancytopenia. Methylmalonic acid and homocystine were found in the urine. The concentration of B12 in the serum was 26 pg/ml. Fibroblasts derived from the patient failed to take up labeled cobalamin in the absence of a source of TCII. Uptake was normal in the presence of TCII. Treatment with parenteral cobalamin reversed the clinical and hematological manifestations of the disease but she developed glossitis when the interval between injections was lengthened. Intestinal absorption of 57Co‐cobalamin was less than 1% and remained abnormal when highly purified human intrinsic factor was given along with the labeled B12. Absorption improved when the labeled B12 was given together with rabbit TCII. The data suggest that TCII as well as intrinsic factor is required for transport of cobalamin from the intestine to the blood.
Three‐generation dominant transmission of the Silver‐Russell syndrome
Authors: Duncan Peter A. , Hall Judith G. , Shapiro Lawrence R. , Vibert Betsy K.
Published: June 2005

We report on 7 patients with the Silver‐Russell syndrome (SRS) in two 3‐generation families. Three patients in each of the families had an undergrowth of the left side of the body when compared with the normal right side. The clinical courses were mild as compared to the severity sometimes described in sporadic cases.

These patients and a review of 190 SRS cases from the literature showed that there were 23 families in which 38 patients had completely expressed SRS. In 17 of the families, multiple maternal relatives had complete or partial expressions of the SRS.

Most SRS patients have been reported to occur sporadically; however, of the 197 propositi analyzed, 19% had more than one affected individual in a family and several different modes of inheritance could have been responsible. Two families (8.7%) had spontaneous dominant mutations (twins) and possible autosomal recessive transmission was present in 4 families (17.4%). Because no male‐to‐male transmission has yet been documented in the 21 families in the literature and the two families reported here, X‐linked dominant inheritance is a possibility in 17 families (74%).

Thus, although sporadic occurrences and genetic heterogeneity appear to be involved in the SRS, dominant inheritance may be a major causal factor.
Nonimmunologic hydrops fetalis: An etiopathogenetic approach through the postmortem study of 59 patients
Authors: Villaespesa A. Ruiz , Mier M. P. Suarez , Ferrer P. Lopez , Baleriola I. Alvarez , Gonzalez J. I. Rodriguez
Published: June 2005

Aiming at increasing our understanding of the various causative factors of nonimmunologic hydrops fetalis (NIHF) and their pathogenetic mechanisms, we have reviewed 59 cases of this condition from a total number of 4,175 pediatric post‐mortem studies performed at the Department of Pathology of the Hospital La Paz from 1967 to 1987.

We found eight cases (13.5%) without clinical, biochemical, or post‐mortem findings justifying the development of hydrops fetalis, seven cases (12%) associated with certain pathologic findings that by themselves do not explain the development of hydrops and, finally, 44 cases (74.5%) in whom pathological findings may explain the development of the condition. Notwithstanding the etiological diversity of this last group, in 31 of these cases (70%), some common pathogenetic features may be recognized, basically a failure of the right ventricle of the heart in the fetus or newborn, due to a primary heart condition, to intracardiac tumors, or to obstructive phenomena at the level of the right venous drainage.

In our opinion, whenever NIHF is diagnosed or suspected, causes of right cardiovascular failure should be investigated, since about 50% of all cases seem to de due to this pathogenetic mechanism.
Mild form of Jeune syndrome in two sisters
Authors: Giorgi P. L. , Gabrielli O. , Bonifazi V. , Catassi C. , Coppa G. V.
Published: June 2005

Jeune syndrome is characterized by respiratory distress, osseous dysplasia, and short stature. Patients generally die during the first months of life. However, some cases with milder clinical manifestations have been described; these cases show characteristic renal involvement of different severity. The authors report on two cases of the mild form of Jeune syndrome in sisters.
Mild phenotypic abnormalities in combined del 9p2 and dup 3p2
Authors: Game K. , Friedman J. M. , Kalousek D. K.
Published: June 2005

Clinically recognizable syndromes have been reported in association with both del 9p2 and dup 3p2. We report on a girl with combined del 9p2 and dup 3p2 with manifestations of both syndromes but who is less severely affected than one would expect.
Distal deletion of chromosome 1q in an adult
Authors: Halal Fahed , Vekemans Michel , Kaplan Paige , Zeesman Suzan
Published: June 2005

An adult patient with mongoloid appearance, profound retardation and autistic‐like behavior was found to have a deletion of the distal bands of chromosome 1q. To our knowledge, this is the oldest patient with distal deletion 1q.
A “new” skeletal dysplasia in two unrelated boys
Authors: Saul Robert A. , Wilson William G.
Published: June 2005

We report on 2 unrelated boys with similar physical and radiographic findings that may represent a “new” skeletal dysplasia. Findings in common include early speech delay, short stature, frontal bossing with a depression over the metopic suture, a narrow nasal root with beaked nose, midfacial hypoplasia with relatively prominent eyes, and brachydactyly with blunt fingers. Radiographic findings include mild irregularities of the vertebral bodies, hypoplasia of the odontoid process, short phalanges with increased distal width, coning and sclerosis of several epiphyses, and overtubulation of the long bones. Although these patients share some manifestations with the floating‐harbor syndrome (Robinson et al.: J Pediatr 113:703–706, 1988), their radiographic changes are distinctive and are not suggestive of a recognized skeletal dysplasia syndrome.
Apparent Smith–Lemli–Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons
Authors: Parnes Sharon , Hunter Alasdair G. W. , Jimenez Carmencita , Carpenter Blair F. , MacDonald Ian
Published: June 2005

A diagnosis of Smith–Lemli–Opitz syndrome was made shortly after birth in a small‐fordates infant, on the basis of a characteristic face, penoscrotal hypospadias, bilateral postaxial hexadactyly, and bilateral syndactyly of toes 2–3. The clinical course was marked by failure to thrive, severe delay, refractory myoclonic jerks beginning at age 2 months, and increasing hepatosplenomegaly. He developed corneal clouding and increased gingival hypertrophy and died at age 18 weeks. Autopsy disclosed widespread storage of mucopolysaccharides and lipids within the macrophages and, to a lesser extent, parenchymal cells, of all organ systems. There was extensive demyelination of the cerebral white matter, and dystrophic calcification in the cerebrum, cerebellum, and brainstem. There was no evidence of primary neuronal involvement in the storage. Although the chance concurrence of 2 uncommon diseases is rare, a causal link between the clinical anomalies and the storage disorder cannot be argued convincingly on the basis of one case. Careful pathologic studies of other children who die with clinical signs compatible with Smith–Lemli–Opitz syndrome are indicated.
Ring chromosome 6: Clinical and cytogenetic behaviour
Authors: Paz‐y‐Miño César , Benítez Javier , Ayuso Carmen , Sánchez‐Cascos Andrés
Published: June 2005

Several investigators have reported in vitro instability of ring chromosomes. We have evaluated the clinical and cytogenetic course over 8 years in a patient with ring chromosome 6 and found stability in this ring chromosome. The different cell lines remained constant, and the phenotype showed little variation. This syndrome seems to be related to the deletion in the ring rather than to its instability.
Autosomal recessive inheritance of a syndrome of hypertelorism, hypospadias, and tetralogy of Fallot?
Authors: Farag Talaat I. , Teebi Ahmad S.
Published: June 2005

We report on 3 brothers with hypertelorism, hypospadias, and tetralogy of Fallot. Parents are first cousins once removed; the father has apparent hypertelorism. An apparently normal paternal uncle who is married to a second cousin also has a daughter with hypertelorism and tetralogy of Fallot. All similarly affected relatives have mild or borderline mental retardation. The combination of anomalies may represent a previously undescribed autosomal recessive disorder.
Detection of molecular rearrangements in Prader‐Willi syndrome patients by using genomic probes recognizing four loci within thePWCR
Authors: Gregory C. A. , Kirkilionis A. J. , Greenberg C. R. , Chudley A. E. , Hamerton J. L.
Published: June 2005

The Prader‐Willi chromosome region (PWCR) in Prader‐Willi Syndrome patients was analyzed by using genomic DNA probes mapping to 15q11.2–q12. The present report includes analysis of dosage by RFLP and densitometric studies, and analysis of restriction patterns. Twelve Prader‐Willi syndrome (PWS) patients were studied: 5 had deletions of 15q11–q13, one had an unbalanced translocation, and 6 were karyotypically nomal. four genomic DNA probes were used: pML34 (D15S9); pTD3–21 (D15S10); IR4‐3 (D15S11), a subclone of IR4; adn IR10‐1 (D15S12), a subclone of IR10 (Donlon et al.:Proc Natl Acad Sci USA83:4408–4412, 1986). The results presented demonstrate that molecular rearrangements have occurred in 10 of the 12 PWS patients investigated and that the specific rearrangements differ from patient to patient. Patients with apparently similar cytogenetic delections differ at the molecular level with deletions and/or duplications of various loci. The present study reports molecular alterations within thePWCRin PWS patinets reported as cytogenetically normal. However, the 6 karyotypically normal patients are a heterogeneous group with molecular rearrangements ranging from none detected to delections and/or duplications. These molecular studies suggest that a physical disruption of thePWCRcauses the PWS not only in those patients reported to have cytogenetic aberration but also in those identified as apparently karyotypically normal. The question remains as to whether the PWS patients in whom a molecular abnormality has not been detected have an autosomal recessive form of PWS, a molecular disruption which has not yet been detected, or another mechanism producing an apparently identical phenotype. The order of the 4 loci on chromosome 15 is hypothesized to be cen →D15S9→D15S12→D15S11→D15S10.
Dynamics of quantitative homeostasis: VIII. Processes that oscillate finitely many times
Authors: Murphy Edmond A.
Published: June 2005

There is no well‐established method of dealing with medical processes that oscillate only a finite number of times. A lagged homeo‐static model of higher power in certain circumstances follows such a pattern and critical values are here explored by numerical integration. Abrupt ending of the oscillation occurs with processes of higher powers. The model is illustrated by clonus, chosen because reflexes are naturally lagged responses and because clonus may be unsustained. In applying the model to clonus, there are some incongruities (notably inertia) that call for caution; however, published data suggest that they may not be important. These imperfections notwithstanding, the correspondence is remarkably good. The model dealt with here, being simple and economical, is a useful first step to genetics; and some empirically testable deductions from the model are listed.
Autosomal dominant tibial hemimelia–polysyndactyly‐triphalangeal thumbs syndrome: Report of a Brazilian family
Authors: Richieri‐Costa A. , de Miranda E. , Kamiya T. Y. , Freire‐Maia D. V.
Published: June 2005

We report on 3 persons in a 3‐generation Brazilian family affected with complex limb defects. The spectrum of limb anomalies ranged from isolated toe syndactyly to severe bilateral tibial aplasia. Radioulnar synostosis was present in 2 of the 3 patients. Clinical and genetic aspects are discussed.
Åland Island eye disease (Forsius‐Eriksson ocular albinism) and an Xp21 deletion in a patient with duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia
Authors: Pillers De‐Ann M. , Weleber Richard G. , Powell Berkley R. , Hanna Cheryl E. , Magenis R. Ellen , Buist Neil R. M.
Published: June 2005

Glycerol kinase deficiency (GKD) has been described in isolation and in complex phenotypes including either congenital adrenal hypoplasia, Duchenne muscular dystrophy, or both. Cytogenetic and molecular studies have localized these defects to a deletion in volving the X chromosome at band Xp21, consistent with its X‐linked recessive pattern of inheritance. Other clinical findings in the complex glycerol kinase deficiency (CGKD) patients are mental retardation, short stature, and hypogonadotropic hypogonadisem.

We report on a 6‐year‐old boy who, in addition to the CGKD phenotype described above, had ocular hypopigmentation consistent with Forsius‐Eriksson ocular albinism, also known as type 2 ocular albinism or Åland Island eye disease. Cytogenetic analysis shows an interstitial deletion in the short arm of the X‐chromosome at Xp21.
Duplication of euchromatin without phenotypic effects: A variant of chromosome 16
Authors: Bryke Christine R. , Breg W. Roy , Potluri Venkateswara R. , Yang‐Feng Teresa L.
Published: June 2005

A family with an unusual variant of chromosome 16 is presented. The mother and son both with additional material present in the short arm of chromosome 16 adjacent to the centromere are phenotypically normal. The extra C‐band negative region has been shown not to be composed of alpha satellite DNA. The literature regarding other familial cases of what appears to be the same variant of chromosome 16 is reviewed.
Terminal deletions of the long arm of chromosome 7: Five new cases
Authors: Bogart Mark H. , Cunniff Christopher , Bradshaw Christy , Jones Kenneth Lyons , Jones O. W.
Published: June 2005

Twenty‐two cases of terminal deletions of the long arm of chromosome 7 have been reported. We present 5 new cases, 3 of which were ascertained due to fetal holoprosencephaly, one due to anencephaly, and one due to multiple structural defects in a 15‐year‐old boy. The presence of holoprosencephaly in 3 of the 5 cases reported herein and in 2 previously reported cases suggests that this manifestation may be commonly observed in individuals with deletion 7q.
Multiple congenital anomalies associated with a 47,XXX chromosome constitution
Authors: Hood Opal J. , Hartwell Elizabeth A. , Shattuck Karen E. , Rosenberg Harvey S.
Published: June 2005

An infant with a 47, XXX chromosome constitution, who died shortly after birth, had laryngeal atresia, pulmonary hypoplasia, craniofacial anomalies, urogenital malformations including unilateral renal agenesis, hydrometrocolpos and ovarian dysgenesis, and mildly abnormal endochondral ossification. Implications for genetic counseling are presented.
Identification of deletion and triple α‐globin gene haplotypes in the montreal β‐thalassemia screening program: Implications for genetic medicine
Authors: Akerman Beverly R. , Fujiwara T. Mary , Lancaster Gerald A. , Morgan Kenneth , Scriver Charles R.
Published: June 2005

We obtained blood samples in a screening program designed to detect β‐thalassemia heterozygotes in Montreal; additional samples were obtained from referred persons. We analyzed DNA for variant numbers of α‐globin genes, notably the α‐thalassemia2(‐ α/), α‐thalassemia1, (– –/), and triplicated ζ‐globin gene (ααα/) haplotypes using restriction enzymes and probes for α‐globin and α‐globin gene sequences. We estimated the numbers of Montreal residents of Italian and Greek ethnic origin with –α/αα genotype. Thus, 4.3% of Italians and 1.5% of Greeks, or about 7,500 persons, are estimated to be α‐thalassemia2, trait (silent carriers), largely (80%) in the –α3.7/type I form. The triplicated α‐globin gene haplotype was also found. The risk of a severe (α‐thalassemia1) phenotype associated with inheritance of – –;/αα or –α/ –α genotypes was low and was found predominantly in this study, in persons of Asian ethnic origin. The sample of Asians was too small to estimate carrier frequencies; however, based on results from the β‐thalassemia screening program, we estimated that about 4% of Asians (about 1,300 persons) in Montreal are α‐thalassemia carriers. We identified persons heterozygous for both β‐thalassemia and α‐thalassemia mutations. In these double heterozygotes, the effect of the triplicated α‐globin gene was to make the erythrocyte parameters used for screening (MCV and %HbA2) more deviant from normal whereas deletion of 2 α‐globin genes tended to normalize the erythrocyte values. These findings have implications for the screening program and reproductive counseling.
A new syndrome of dwarfism, brachydactyly, nail dysplasia, and mental retardation in sibs
Authors: Tonoki Hidefumi , Kishino Tatsuya , Niikawa Norio
Published: June 2005

We describe a new multiple congenital anomaly/mental retardation (MCA/MR) syndrome in chromosomally normal sibs. Both had microcephaly, a “coarse” face with synophrys, ear anomalies, type B brachydactyly, nail dysplasia, skeletal anomalies, dwarfism, and mental retardation. Their mother had nail dysplasia, mild mental retardation, and short stature. An uncle, a younger brother of the mother, died at 17 years of age and also had a “coarse” face, digital anomalies, dwarfism, and severe mental retardation. The malformation complex in this family apparently has not been described previously, and the manifestations of the patients do not correspond to those of any known malformation syndrome. The disorder may be attributable to the pleiotropic effect of an autosomal dominant or an X‐linked semidominant gene.
Partial duplication 1q: Report of four patients and review of the literature
Authors: Rasmussen Sonja A. , Frias Jaime L. , Lafer Charlotte Z. , Eunpu Deborah L. , Zackai Elaine H.
Published: June 2005

Here we report on 4 unrelated patients with reciprocal translocations which resulted in duplication of the distal portion of chromosome 1q. Although the patients had certain non‐specific malformations in common, our investigation and a review of the literature do not suggest the existence of a distinct phenotype due to this chromosome abnormality. We think that the coexisting deletion present in each of these patients is responsible for most of the observed differences in clinical manifestations. The variable phenotype makes clinical recognition difficult and precludes making a long‐term prognosis.