bluuebunny/crossref_metadata_2025 huggingface dataset:
Hand and foot length in Prader‐Willi syndrome
Authors: Hudgins Louanne , Cassidy Suzanne B.
Published: June 2005

Small hands and feet (acromicria) are often cited as manifestations in the Prader‐Willi syndrome (PWS), but it has been our experience that these are not universal findings. To address this issue, we obtained longitudinal and cross‐sectional data, retrospectively and prospectively, including height, hand length, and foot length, on 56 patients with PWS who are followed in the multidisciplinary PWS clinic at the University of Connecticut Health Center. Hand and foot lengths were plotted using two published sets of normative data. In addition, height age was calculated on each measurement of stature so that the corresponding hand and foot measurements could be compared to those expected for height, rather than age, as many PWS individuals are short. Foot length was proportionately smaller than hand length in all individuals; this difference was more striking in females. By age 12 years, almost all individuals had a footlength <25th centile for chronological age and <50th centile for height age. Female hand length was also <25th centile for chronological by age 12 years and <50th centile for height age in almost all cases. Male hand length data appeared to fall more within the normal range until adulthood, although fewer data were available. Black individuals with PWS had relatively larger hands and feet than their Caucasian counterparts. Many people with PWS had hand and foot lengths which fell within the normal range, particularly those under the age of 12 years and those whose height was >50th centile for age. Therefore, clinicians should use hand and foot lengths prudently as a diagnostic criterion when evaluating individuals for PWS.
Interstitial deletion of chromosome 18[del(18)(q11.2q12.2 or q12.2q21.1]
Authors: Surh Linda C. , Ledbetter David H. , Greenberg Frank
Published: June 2005

A 27‐month‐old boy with mild developmental delay, growth delay, strabismus, midface hypoplasia, relative telecanthus, downslanting palpebral fissures, epicanthal folds, dental hypoplasia, and cardiac defects was found to have an interstitial deletion of chromosome 18 involving band q12.1 or q12.3.
Concordance of auriculo‐cardiovascular‐skeletal malformations: A new malformation complex in an infant of a diabetic mother?
Authors: Berkenstadt Michal , Shtrausberg Rachel , Goodman Richard M. , Katznelson Mariassa Bat‐Miriam , Goldman Boleslav , Barkai Gad
Published: June 2005

The incidence of malformations among infants of diabetic mothers (IDM) is known to be higher than in the general population. These malformations usually involve several organ systems and in the past few years there has been an attempt to group them into distinct “syndromes.” The present report concerns a child with a specific constellation of findings not yet reported in the infant of a diabetic mother, and we drge our colleagues to look for other associations existing in these infants, rather than just listing series of individual malformations.
Marshall syndrome
Authors: Stratton Robert F. , Lee Brendan , Ramirez Francesco
Published: June 2005

We report on a mother and daughter with Marshall syndrome, with the Robin sequence present in the daughter. Results of our efforts to link this syndrome to a defect in type II collagen are reported. We compare and contrast Marshall syndrome with the Stickler syndrome, and propose that enough phenotypic overlap exists to suggest that they are probably allelic expressions of the same locus.
Denaturing gradient gel electrophoresis of the α1‐antitrypsin gene: Application to prenatal diagnosis
Authors: Dubel Jacqueline R. , Finwick Raymond , Hejtmancik J. Fielding
Published: June 2005

A method for detection of the M and Z alleles of the alpha 1‐antitrypsin deficiency (AAT) gene has been developed using denaturing gradient gel electrophoresis (DGGE) of DNA samples amplified in vitro by the polymerase chain reaction. Amplification of the 90 nucleotides surrounding the Z mutation site with concurrent attachment of a 40 bp GC‐rich region yields DNA fragments that are easily and quickly separated by DGGE. Results are consistently attained in 1–2 days, making this one of the most rapid method of diagnosis of AAT deficiency to date. Additionally, the analyses are completed entirely without the use of radioactive probes, thus eliminating the problems and precautions that are inherent with the use of32P. The simplicity and reliability of this technique make it well suited for routine use in diagnostic laboratories.
Cerebro‐oculo‐facio‐skeletal syndrome: Further delineation
Authors: Gershoni‐Baruch Ruth , Ludatscher Ruth M. , Lichtig Chaim , Sujov Polo , Machoul Imad
Published: June 2005

We report on a newborn infant with cerebrooculo‐facio‐skeletal (COFS) syndrome. Congenital muscular dystrophy‐like changes were present in this patient. It is debated whether the clinical spectrum of the COFS phenotype should be expanded to include congenital muscular dystrophy:
Diagnosis of twin zygosity by hypervariable RFLP markers
Authors: Akane Atsushi , Matsubara Kazuo , Shiono Hiroshi , Yamada Masao , Nakagome Yasuo
Published: June 2005

The application of variable number of tandem repeat (VNTR) markers to the determination of twin zygosity was investigated. In the first case, which was performed with the use of six VNTR markers, the probability of monozygosity, calculated from Essen‐Möller's formula II, was 0.99972. In the other three cases in which four VNTR markers were analyzed, the probabilities were 0.98251–0.99557. These results suggest that VNTR markers are useful for determination of twin zygosity.
High resolution replication banding combined with in situ hybridization for the delineation of a subtle chromosome rearrangement
Authors: Qumsiyeh Mazin B. , Wilroy R. Sid , Peeden Joseph N. , Tharapel Avirachan T.
Published: June 2005

Molecular cytogenetic techniques were used to delineate a subtle chromosome rearrangement in an infant with growth and psychomotor retardation, abnormal scalp hair pattern, narrow palpebral fissures, broad nasal bridge, bulbous nose, small nostrils, thin lips in a cupid's bow configuration, bilateral simian creases, and unilateral cryptorchidism. Analysis using GTG‐banded chromosomes at about 400 band level showed no obvious abnormality. Prometaphase analysis at about 600 band level showed an extra band at 14q32 on GTG‐banding. The father had the same extra band suggesting a reciprocal translocation but the second chromosome involved in the translocation could not be identified. High resolution replication banding on the father's lymphocytes showed a balanced reciprocal translocation 46,XY,rcp(8;14)(q24.1;q32.1). The translocation was confirmed by in situ hybridization with an immunoglobulin heavy chain probe which maps to 14q32.3. The infant therefore had duplication of 8q24.1→qter and deficiency of 14q32.1→qter. His phenotype resembled that of patients with partial duplications of the distal long arm of chromosome 8.
PCR detection of distal Yp sequences in an XX true hermaphrodite
Authors: Nakagome Yosuo , Seki Satoko , Fukutani Keiko , Nagafuchi Shigeo , Nakahori Yutaka , Tamura Takashi
Published: June 2005

An XX true hermaphrodite was examined for the presence of Y‐specific sequences using Southern‐blotting and polymerase chain reaction (PCR) techniques. of 25 loci examined, only two, the proximal border of the pseudoautosomal region (PABY) and the sex determining region of the Y chromosome (SRY), were detected. A crossing over event in paternal meiosis, proximal to the SRY locus but distal to the zinc finger protein (ZFY) locus, presumably transferred to two loci to the chromosome.
Otto Ullrich and his syndromes
Authors: Wiedemann Hans‐Rudolf
Published: June 2005

A half‐century ago Otto Ullrich became the first clinical geneticist to assume the Chairmanship of a clinical department in a medical school. Clinical genetics owes Ullrich the delineation and definition of several important genetic diseases and syndromes, most importantly the condition named after him and Henry Turner. This paper reports on Ullrich's teacher, his career, his personality, and “his” syndromes.
Value of clinical analysis in epidemiological research: The Spanish registry experience
Authors: Martínez‐Frías M. L. , Frías J. L. , Rodríguez‐Pinilla E. , Urioste M. , Bermejo E. , Cereijo A. , Gaya F.
Published: June 2005

Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), a hospital‐based, case‐control study and surveillance program, we investigated the potential value of registry systems in the identification of causes of congenital defects when their methodology includes (1) detailed reporting and coding of all anomalies present in each child, whether major or minor, (2) clinical analysis and coding of the global pattern of anomalies present in each infant, and (3) classification of all children studied according to their clinical presentation.

These approaches provide great specificity and flexibility in the retrieval and analysis of data. Not only do they permit the study of specific anomalies, but also the analysis of children with MCA patterns, as well as the study of the relationship of specific defects with the rest of the anomalies present in a child.

To illustrate this point, we present general data on 15,307 malformed children and more specific information on 153 cases of anal atresia/stenosis identified among the 753, 410 livebirths surveyed by the ECEMC between April 1976 and September 1989.
Familial renal‐hepatic‐pancreatic dysplasia and Dandy‐Walker cyst: A distinct syndrome?
Authors: Hunter A. G. W. , Jimenez C. , Tawagi F. G. R.
Published: June 2005

Ivemark et al. first described sibs with renal‐hepatic‐pancreatic dysplasia (RHPD) (Ivemark BI, Oldfelt V, Zetterström R (1959): Acta Pediatr Scand 48:1–11). Subsequent reports of affected individuals have described additional malformations and syndromes associated with RHPD. In this paper we describe 2 sibs with RHPD in association with Dandy‐Walker cyst (DW). Through an examination of the pattern of associated malformations seen in RHPD we argue that RHPD‐DW is a distinct monogenetic syndrome, and not an association.
Acceptance of chorionic villus sampling in the southwest region of the Netherlands: A 5‐Year evaluation
Authors: Brandenburg H. , Jahoda M. G. J. , Los F. J. , Wladimiroff J. W.
Published: June 2005

The acceptance of chorionic villus sampling (CVS) for monitoring pregnancies at risk for chromosomal and genetic disorders was studied from its introduction in the Centre for Clinical Genetics in Rotterdam in 1984 until 1988. Special attention was given to increasing acceptance in the group with advanced maternal age (AMA) (12.6% CVS in 1984, 52.2% CVS in 1988) and the group with a high genetic risk (HGR) (42.7% in 1984, 86.7% in 1988). The odds‐growth‐rate in CVS was 1.64 and 1.67 respectively, which was not significantly different. The relatively limited use of CVS at AMA is most likely determined by the fact that a considerable number of patients are referred too late in pregnancy to have the option of CVS.
Attitudes toward presymptomatic testing and prenatal diagnosis for adrenoleukodystrophy among affected families
Authors: Costakos Deborah , Abramson Ruth K. , Edwards Janice G. , Rizzo William B. , Best Robert G.
Published: June 2005

One hundred and thirty‐six individuals with a family history of X‐linked adrenoleukodystrophy (ALD) or adrenomyeloneuropathy (AMN) were given a questionnaire surveying their sociodemographic characteristics, knowledge of X‐linked inheritance, and attitudes toward prenatal, presymptomatic, and carrier testing. Of the respondents, 68% indicated that they would use prenatal testing. Of these, 57.1% would terminate a pregnancy of a male fetus hemizygous for the ALD gene and 13.5% would reportedly choose to terminate a heterozygote female fetus. Presymptomatic testing would be used by 88.7% of respondents to test at‐risk sons and carrier testing would reportedly be used by 95.4% of respondents to test their at‐risk daughters. Respondents correctly answered an average of 61% of the questions testing understanding of X‐linked inheritance. This indicates a strong interest in prenatal, presymptomatic, and carrier testing and a need for genetic counselors to provide information about these available tests and X‐linked inheritance.
Mitochondrial DNA deletion in a girl with manifestations of Kearns‐Sayre and Lowe syndromes: An example of phenotypic mimicry?
Authors: Moraes Carlos T. , Zeviani Massimo , Schon Eric A. , Hickman Robert O. , Vlcek Brien W. , DiMauro Salvatore
Published: June 2005

Lowe oculocerebrorenal syndrome is an X‐linked recessive disease whose locus has been assigned to Xp25. However, several reports of affected females without obvious chromosomal abnormalities suggest genetic heterogeneity of the Lowe phenotype. Although the biochemical defect in typical Lowe syndrome is not known, there is evidence suggesting that mitochondrial metabolism may be impaired. We have studied a girl who presented with an oculocerebrorenal syndrome, but later developed symptoms and signs of mitochondrial encephalomyopathy. Molecular genetic analysis of muscle mitochondrial DNA showed the presence of a population of partially deleted mtDNAs (heteroplasmy). The deletion was 7803 bp long and encompassed several genes encoding subunits of the respiratory chain enzymes. Our results suggest that mitochondrial DNA deletions may mimic several symptoms of the Lowe phenotype and reinforce the concept that a defect of mitochondrial metabolism could be involved in the pathogenesis of the X‐linked disease.
Prenatal ascertainment of an inherited dup(18p) associated with an apparently normal phenotype
Authors: Wolff Daynna J. , Raffel Leslie J. , Ferré Merry M. , Schwartz Stuart
Published: June 2005

Direct two‐generation transmission of an unbalanced 18p + chromosome was discovered after amniocentesis. Neither the mother nor the child exhibited apparent physical malformations or mental impairment. Banding analysis suggested a complete 18p duplication. Molecular studies verified the 18p origin of the duplicated material. Only 14 previous cases of duplication 18p have been reported and these exhibited either a normal phenotype or mild and inconsistent abnormalities. The present cases, as well as the review of literature, indicate that duplication 18p is associated with few or inapparent phenotypic abnormalities.
Delineation of the costello syndrome
Authors: Martin Rick A. , Jones Kenneth Lyons
Published: June 2005

We present a 15‐year‐old girl with mental retardation, short stature, coarse face, unusually thick, loose skin of the hands and feet, deep plantar and palmar creases, and nasal papillomata. Her history and physical findings are compared to those of 2 children initially reported by Costello and to 1 child recently reported by Der Kaloustian et al.
Pallister‐killian syndrome: Characterization of the isochromosome 12p by fluorescent In Situ hybridization
Authors: Speleman Frank , Leroy Jules G. , Van Roy Nadine , De Paepe Anne , Suijkerbuijk Ron , Brunner Han , Looijenga Leendert , Verschraegen‐Spae Marie‐Rose , Orye Edward
Published: June 2005

The isochromosome 12p (i(12p)) in fibroblasts of 3 patients with Pallister‐Killian syndrome and one deceased prematurely born neonate, was characterized by fluorescent in situ hybridization (FISH) using chromosome 12‐specific DNA probes. FISH is a useful technique for rapid and reliable detection and characterization of the i(12p) chromosome in Pallister‐Killian patients. Detection was possible also in interphase cells. In addition, the in vitro selection against i(12p) cells at different passages in fibroblast cultures of two patients was monitored.
New form of postaxial acrofacial dysostosis?
Authors: Arens Raanan , Reichman Brian , Katznelson Mariassa Bat‐Miriam , Goodman Richard M.
Published: June 2005

We report on a 2‐month‐old Sephardic Jewish girl with bilateral and symmetrical deficiency of the fifth digital rays of all 4 limbs, combined with severe deformations and other malformations of the limbs. These findings were associated with orofacial malformations, as well as with visceral anomalies differing from those found in other postaxial deficiency syndromes. Parents were closely consanguineous. We assume this patient represents a new form of postaxial acrofacial dysostosis.
Autosomal recessive cerebellar hypoplasia and endosteal sclerosis: A newly recognized syndrome
Authors: Charrow Joel , Poznanski Andrew K. , Unger Frances M. , Robinow Meinhard
Published: June 2005

We describe a brother and sister and an unrelated boy with congenital cerebellar hypoplasia and endosteal sclerosis. All 3 children presented with ataxia and developmental delay, and were found to have microcephaly, short stature, oligodontia, strabismus, nystagmus, and congenital hip dislocation. A previously published case is reviewed. The disorder appears to represent a newly recognized autosomal recessive syndrome.
Tracheomalacia in Hallermann–Streiff Syndrome
Authors: Salbert Bonnie Anne , Stevens Cathy A. , Spence J. Edward
Published: June 2005

We report on a white boy with Hallermann–Streiff syndrome (HSS) who also had tracheomalacia. Chronic respiratory insufficiency led to biventricular failure and death at age 6 months. There have been no previously reported cases of Hallermann–Streiff syndrome with documented tracheomalacia. However, there may be cases in which tracheomalacia may have been present, but not diagnosed. The literature contains 6 HSS cases with severe respiratory symptoms. Tracheomalacia should be considered in a patient with HSS who presents with an unusual cry, stridor, choking, or apnea. With the availability of surgery and supportive treatment, early diagnosis of tracheomalacia in these patients may prevent death and secondary neurologic insult from acute hypoxia.
Complete sequence of human cardiac α‐myosin heavy chain gene and amino acid comparison to other myosins based on structural and functional differences
Authors: Matsuoka Rumiko , Beisel Kirk W. , Furutani Michiko , Arai Shoichi , Takao Atsuyoshi
Published: June 2005

We have obtained the 5820 nucleotide sequence encoding all 1939 amino acids of the human cardiac α‐myosin heavy chain (α‐MHC

The sequence has been deposited in the DDBJ base. (Accession no. D00943)

), as established by dideoxy sequencing of cloned cDNA, genomic DNA and polymerase chain reaction (PCR) amplification products. This sequence represents overlapping fragments of the entire coding sequence. Amino acid sequence comparison of the human cardiac α‐MHC with the published human cardiac β‐MHC have demonstrated that there are, at least, 7 isoform‐specific divergent regions, including functionally important binding protein‐related sites such as ATP, actin and myosin light chain. It has been reported that in the rat, there are 8 isoform‐specific divergent regions. The 7th divergent area (residue area 1633‐1657, which is thought to mediate thick filament formation) in the light meromyosin region in the rat is not apparent in the human. The amino acid compositions of cardiac α‐ and β‐MHCs in the human and the rat, and human embryonic skeletal muscle and chicken gizzard smooth muscles were compared. Amino acid sequences in cardiac α‐ and β‐MHCs in the human and the rat are well conserved. In the head portion, the amino acid composition divergence of human cardiac α‐MHC is ranked between rat cardiac α‐MHC and human cardiac β‐ or rat cardiac β‐MHC; human skeletal muscle MHC is the most divergent of the myosin isoform examined. These data predict that human cardiac α‐MHC may have undergone evolutionary changes toward obtaining the biochemical and physiological properties of cardiac β‐MHC.
Autosomal dominant inheritance of tetramelic monodactyly
Authors: Sommer Annemarie , Hines Stefani J.
Published: June 2005

We report on tetramelic monodactyly with autosomal dominant inheritance. The propositus and all affected relatives had only digital malformations as determined by physical examination or history. Since it could not be determined that the involved digits of the propositus or relatives were fifth fingers and toes, we conclude this to be the first report of this type of hand and foot malformation with autosomal dominant inheritance.
Diagnostic value of ophthalmologic findings in myotonic dystrophy: Comparison with risks calculated by haplotype analysis of closely linked restriction fragment length polymorphisms
Authors: Ashizawa T. , Hejtmancik J. F. , Liu J. , Perryman M. B. , Epstein H. F. , Koch D. D.
Published: June 2005

To determine diagnostic value of lens opacities in myotonic dystrophy (DM), we examined 98 at‐risk members of 9 DM kindreds. Haplotype analysis of restriction fragment length polymorphisms (RFLPs) using ApoC2, CKMM, and pEFD4.2 supported the diagnosis of DM in 33 and excluded the diagnosis in 51 members. The sensitivities of bilateral iridescent lens opacities, posterior cortical lens opacities, orbicularis oculi weakness, low intraocular pressure, ptosis, and ocular myotonia were 46.7, 50.0,60.6,59.3,51.5, and 3.0%, while their specificities were 100.0, 100.0, 98.0, 94.1, 96.1, and 100.0%, respectively. A peripheral pigmentary degeneration and central macular lesions of retina were not found on indirect fundoscopy. In 86.2% of DM patients, bilateral iridescent lens opacities, posterior cortical lens opacities, or both were present. Unilateral iridescent lens opacities occurred in only 3 of our DM patients, and 2 of non‐DM relatives showed a few unilateral iridescent particles. Posterior cortical lens opacities in DM patients always affected both eyes in this series. We conclude that 1) bilateral iridescent lens opacities and posterior cortical lens opacities are highly specific for DM and useful for establishing clinical diagnosis of DM, 2) unilateral iridescent lens opacities are infrequent in DM and are seen in some non‐DM members, and 3) ocular myotonia and clinical retinopathies are rare in DM.
Head circumference of children with Down syndrome (0–36 months)
Authors: Palmer Christina G. S. , Cronk Christine , Pueschel Siegfried M. , Wisniewski Krystyna E. , Laxova Renata , Crocker Allen C. , Pauli Richard M.
Published: June 2005

This study provides statistically appropriate head circumference reference curves for males and females with Down syndrome (DS) from birth to 36 months of age. A total of 239 males and 182 females from five study populations, yielding a combination of cross‐sectional and longitudinal data, were used for the analysis. The method of least squares was used to test the fit of the growth model y = a + bx + c[log(x + 1)], where x is age in months. These standardized curves should provide information of value in the medical, physical, and developmental management of children with DS.
Pentalogy of Cantrell and associated midline anomalies: A possible ventral midline developmental field
Authors: Carmi Rivka , Boughman Joann A.
Published: June 2005

Five cases of the Pentalogy of Cantrell (PC), ascertained through the Baltimore–Washington population‐based study of infants with congenital cardiovascular malformations, represent a regional prevalence of 5.5/1 million liveborn infants for this disorder. Three of these patients had cleft lip with or without palate. Review of the reported literature of the Pentalogy of Cantrell and various combinations of the anomalies within the spectrum of this pentad suggests that the PC defines a specific midline ventral developmental field. Cleft lip with or without cleft palate and encephalocele tend to specifically associate with ventral midline anomalies within the spectrum of PC. These associations might either illustrate the previously observed tendency of specific occurrence of certain combinations of midline defects or represent defined subunits of the midline developmental field.
Rett syndrome: A search for gene sources
Authors: Åkesson Hans Olof , Hagberg Bengt , Wahlström Jan , Engerström Ingegerd Witt
Published: June 2005

A series of 77 Swedish females with classical Rett syndrome were genealogically traced as far back as possible, in most cases to 1720–1750, or 7–10 generations. Details were collected concerning approximately 8,000 ancestors. Common ancestry was seen in 2 pairs of females with Rett syndrome. Thirty‐nine of the 77 Rett females were traced to 9 small and separate rural areas, and 17 pairs even came from the same farm or homestead. The common origin was found equally often among descendants of the father as of the mother. In 9 cases, the father came from one and the mother from another of the 9 specific “Rett areas.” These observations, combined with the finding of a raised rate of consanguineous marriages in the paternal as well as in the maternal ancestry, point to a genetic transmission. Analyses of parental ages at birth and of birth order gave normal results.
Deletion of chromosome 15pter→q11.2 due to t(Y;15) in a boy with Prader‐Willi syndrome
Authors: Qumsiyeh Mazin B. , Dalton James D. , Gordon Patricia L. , Wilroy R. Sid , Tharapel Avirachan T.
Published: June 2005

Chromosome analysis of lymphocytes from a patient with the clinical presentation of Prader‐Willi syndrome showed the presence of 45 chromosomes, including a der(Y) resulting from an unbalanced t(Y;15)(q12;q11.2). In situ hybridization using DYZ3 and DYZ2 showed positive signals at the paracen‐tromeric region on the short arm and at the heterochromatic region of the long arm of the Y chromosome, respectively. The Prader‐Willi syndrome in this patient is caused by the deficiency of a very small region involving 15cen→q11.2.
Ectodermal dysplasia, ectrodactyly, clefting, anophthalmia/microphthalmia, and genitourinary anomalies: Nosology of Goltz‐Gorlin syndrome versus EEC syndrome
Authors: Rodini E. S. O. , Nardi A. , Guion‐Almeida M. L. , Richieri‐Costa A.
Published: June 2005

We report on two unrelated Brazilian girls born to normal and nonconsanguineous parents and presenting ectodermal dysplasia, ectrodactyly, clefting, tear duct anomalies, and micro/anophthalmia. The clinical picture presented by these patients suggests the diagnosis of Goltz‐Gorlin (Focal dermal hypoplasia) syndrome and EEC syndrome.
Intrafamilial variability in cleidocranial dysplasia: A three generation family
Authors: Chitayat David , Hodgkinson Kathy A. , Azouz E. Michel
Published: June 2005

We present a 3‐generation family, ascertained after the birth of a child with cleidocranial dysplasia (CCD). The propositus presented with respiratory distress (due to a narrow thorax) and hypoplasia and discontinuity of both clavicles. The mother, aunt, and grandmother had varied features of the condition. This intrafamilial variation illustrates the need for clinical assessment of family members following the birth of an apparent sporadic case of CCD.
Pulmonary atresia with intact ventricular septum and hypoplastic right heart in sibs: A single gene disorder?
Authors: Chitayat David , McIntosh Nathalie , Fouron Jean‐Claude
Published: June 2005

We report on 2 sisters with hypoplastic right heart and pulmonary atresia. The first sib was found to have pulmonary atresia, intact ventricular septum, and hypoplastic right heart after delivery. Fetal echocardiography at 22 weeks of gestation during the second pregnancy documented the same cardiac abnormalities. Autopsy findings in the fetus confirmed the echocardiographic findings. No other malformations were detected in either case, and no other affected relatives were identified. We suggest that this rare congenital heart defect may, in some cases, be an autosomal recessive trait.
Ebstein anomaly: Report of a familial occurrence and prenatal diagnosis
Authors: McIntosh Nathalie , Chitayat David , Bardanis Marietta , Fouron Jean‐Claude
Published: June 2005

The Ebstein anomaly is a rare congenital heart disease involving the position and structure of the tricuspid valve. Although most cases are sporadic, familial occurrence has been documented. We report on 2 sisters, born to consanguineous parents, who were diagnosed prenatally with severe Ebstein anomaly.
Acrofacial dysostosis syndrome type Rodriguez: A new lethal MCA syndrome
Authors: Petit Paul , Moerman Philippe , Fryns Jean‐Pierre
Published: June 2005

We present a female fetus with the lethal acrofacial dysostosis syndrome recently delineated by Rodriguez et al. [1990]. The present findings confirm that this syndrome constitutes a true MCA syndrome in which mandibulofacial dysostosis and severe limb reduction defects are associated with complex malformations of different organs and systems especially the CNS, the urogenital tract, heart, and lungs.
Terminal transverse limb defects associated with familial cavernous angiomatosis
Authors: Filling‐Katz Michele R. , Levin Sondra W. , Patronas Nicholas J. , Katz Norman N. K.
Published: June 2005

Terminal transverse limb defects rarely are reported as familial. Multiple pathogenetic mechanisms, including vascular disruption, have been proposed to account for these defects. We report on a family followed over the past 6 years known to have familial cavernous angiomatosis in which 2 relatives have similar terminal transverse defects at the mid‐forearm. Multiple relatives have had episodic bleeding from intracranial cavernous angiomas, a distinct finding in this disorder. Other findings in this family include retinal cavernous angiomas (2 patients), a high incidence of skin angiomas (12 patients), cavernous angiomas of the soft tissue (2 patients), and a hepatic angioma (one patient). One of the 2 individuals with the limb defect was evaluated extensively. Magnetic resonance imaging of the forearm with the terminal transverse defect using gadolinium‐DTPA enhancement showed abrupt termination of all structures distal to the normal radial and ulnar heads. We propose that familial cavernous angiomatosis may be a new cause of vascular disruption resulting in terminal transverse limb defects.
Gelsolin gene mutation—at codon 187—in familial amyloidosis, Finnish: DNA‐diagnostic assay
Authors: Haltia Matti , Levy Efrat , Meretoja Jouko , Fernandez‐Madrid Ivan , Koivunen Olli , Frangione Blas
Published: June 2005

Familial amyloidosis, Finnish (FAF), is an autosomal dominant form of systemic amyloidosis with lattice corneal dystrophy and progressive cranial neuropathy as principal clinical manifestations. We have shown that the novel amyloid fibril protein found in these patients is an internal degradation fragment of gelsolin, an actin‐binding protein, and that it contains an amino acid substitution, asparagine for aspartic acid at position 15, that is due to a guanine‐to‐adenine transversion corresponding to codon 187 of human plasma gelsolin cDNA. To test that this mutation cosegregates with the disease high‐molecular‐weight genomic DNA was isolated from autopsied tissues or lymphocytes of 23 patients, 6 healthy relatives and 20 unrelated healthy control persons. Specific fragments were amplified with the polymerase chain reaction for oligonucleotide hybridization analysis using the slot‐blot technique. The guanine‐to‐adenine transversion was found in all FAF patients tested, but in none of the control subjects. Our results show that the mutation (G to A) cosegregates with the disease phenotype, and that the slot‐blot analysis can be used as a diagnostic assay, including prenatal evaluation.
Cystic fibrosis mutations in French Canadians: Three CFTR mutations are relatively frequent in a Quebec population with an elevated incidence of cystic fibrosis
Authors: Rozen Rima , De Braekeleer Marc , Daigneault Jocelyne , Ferreira‐Rajabi Leonor , Gerdes Maria , Lamoureux Linda , Aubin Gervais , Simard Fernand , Fujiwara T. Mary , Morgan Kenneth
Published: June 2005

The French‐Canadian population in the Saguenay‐Lac St. Jean region of northeastern Quebec has an elevated frequency of cystic fibrosis (CF). The average incidence of cystic fibrosis was 1 in 891 births and the prevalence of CF carriers was estimated to be 1 in 15. We tested for 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 133 French‐Canadian CF families from Quebec. Ninety‐one families were from the Saguenay‐Lac St. Jean region and 42 families were referred from other regions of Quebec. We detected the CFTR mutation in 93 and 92% of the CF chromosomes in the Saguenay‐Lac St. Jean and the major‐urban Quebec families, respectively. The two groups of French‐Canadian families were significantly different for the proportions of CFTR mutations. The three most common mutations in the Saguenay‐Lac St. Jean families were ΔF508 (58%), 621 + 1G → T (23%), and A455E (8%); and in the major‐urban Quebec families were ΔF508 (71%), 711 + 1G → T (9%), and 621 + 1G → T (5%). These results provide evidence for the role of founder effect in the elevated incidence of cystic fibrosis in the Saguenay‐Lac St. Jean population.
Baller‐Gerold syndrome: Case report and clinical and radiological review
Authors: Dallapiccola Bruno , Zelante Leopoldo , Mingarelli Rita , Pellegrino Michele , Bertozzi Vincenzo
Published: June 2005

The major manifestations of the Baller‐Gerold syndrome (BGS) are craniosynostosis and preaxial limb anomaly involving the radius and/or the thumb. We report on a new patient with coronal and sagittal suture involvement, mild unilateral radial and thumb hypoplasia, imperforate anus, rectovaginal fistula, prenatal onset growth deficiency, and mental retardation. This patient also had some minor oralfacial anomalies, severe nonfamilial myopia, bilateral conductive hearing loss, ureteric reflux, and skeletal anomalies other than those noted in the skull and upper limbs. This patient confirms the clinical variability among the patients and the wide pleiotropic effects of the BGS gene.
Ankyloblepharon filiforme adnatum
Authors: Weiss Avery H. , Riscile Gisele , Kousseff Boris G.
Published: June 2005

We treated 4 infants with ankyloblepharon filiforme adnatum (AFA), an uncommon anomaly in which the apposing eyelid margins are connected by abnormal tissue strands. One infant had AFA alone, one had Hay–Wells syndrome, characterized by ectodermal dysplasia, and the other 2 had chromosome abnormalities, trisomy 18, and complex chromosome rearrangement, with visceral malformations. Despite heterogeneity and phenotypic variability, these developmental abnormalities shared (1) involvement of tissues growing in apposition and (2) temporal overlap of their occurrence. This suggests a common defect in the mechanism(s) that regulate tissue fusion at multiple sites during development.
New case of Toriello‐Carey syndrome
Authors: Lacombe Didier , Creusot Gérard , Battin Jacques
Published: June 2005

A new syndrome was identified by Toriello and Carey (Am J Med Genet 31:17–23, 1988), based on the description of four children, three of whom were sibs. The main manifestations included agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, retrognathia, abnormal ears, laryngeal and cardiac anomalies, brachydactyly, and hypotonia. We describe findings in a patient, presumed to be another case of the Toriello‐Carey syndrome, which extend the phenotype of the syndrome.
Gastroesophageal dysfunction in Brachmann–de Lange syndrome
Authors: Rosenbach Y. , Zahavi I. , Dinari G.
Published: June 2005

Two children with the Brachmann–de Lange syndrome and severe gastroesophageal reflux are described. Both had esophagitis, recurrent severe anemia, and one had recurrent episodes of aspiration pneumonia and clubbing. Medical treatment failed in both children. One child responded dramatically to surgery, but the other died before surgery could be attempted.

Our experience and a review of the literature suggest that early recognition and surgical treatment of gastroesophageal reflux will reduce morbidity and mortality in children with this syndrome.
Comparison of couples referred and not referred for genetic counseling in a genetic clinic after the birth of a child with a congenital anomaly: A study in a population in the northeastern Netherlands
Authors: Cornel Martina C. , van Essen Anthonie J. , ten Kate Leo P.
Published: June 2005

After the birth of a child with a congenital anomaly, parents have many questions about cause, prognosis, and recurrence risk. An important means of transmitting such information is referral to a genetic clinic. We were interested in knowing what determines whether or not parents are referred for genetic counseling. Data from the local registration of congenital anomalies in the northeastern Netherlands (birth years 1981–1986; 1,217 children/fetuses) and data of the local genetic clinic were compared. The parents of 204 cases (16.8%) had been referred for genetic counseling. Of the couples referred, 76% were referred within one year after birth, usually by a pediatrician (48%). Parents of children with a single anomaly, recognized syndrome, or multiple anomalies not recognized as a syndrome were referred in 5%, 43%, and 26% of cases, respectively. Parents of liveborn children who died were referred in 38% of cases, parents of liveborn/still‐alive and stillborn children in 13% and 22%, respectively. Previous affected sibs and absence of previous livebirths increased the likelihood of referral.
Preaxial polydactyly of feet in infants of diabetic mothers: Epidemiological test of a clinical hypothesis
Authors: Martínez‐Frías María Luisa , Bermejo Eva , Cereijo Ana
Published: June 2005

Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we tested the hypothesis of Carey et al. (Proc Greenwood Genet Cent 9:95), (1990) on maternal diabetes and preaxial polydactyly of feet in infants born to diabetic mothers. Our results seem to confirm their suggestion, although the hallucal type of preaxial polydactyly that they described seems to be much less frequent. Nevertheless, a high risk exists (OR = 24.60, P = 0.0004) for preaxial polydactyly of the feet in relation with other types of birth defects or postaxial polydactyly. This analysis shows the importance of clinical observations for epidemiologists, because such observations constitute hypotheses and provide actual issues for study, and clinicians will get epidemiological confirmation for their individual observations and hypotheses.
Psoriasis vulgaris, fetal growth, and genomic imprinting
Authors: Traupe Heiko , van Gurp Petra J. M. , Happle Rudolf , Boezeman Jan , van de Kerkhof Peter C. M.
Published: June 2005

We report on 2 independent lines of evidence suggesting genomic imprinting of a major gene for psoriasis vulgaris. First, the birth weight of children from psoriatics is influenced by the sex of the psoriatic parent. Children from fathers with psoriasis are considerably (270 g) heavier than children from mothers with psoriasis (P<0.004). Second, the disease manifestation (penetrance) depends in part on the sex of the psoriatic parent. Offspring from fathers with psoriasis and male “gene carriers” are significantly (P<0.015 and P<0.007) more often affected than offspring from mothers with psoriasis and female “gene carriers.” Of 91 grandchildren with psoriasis 59 (65%) have an affected grandfather and 32 (35%) a psoriatic grandmother. This deviation from the expected distribution is significant (P<0.04). Genomic imprinting is considered a special case of epigenetic modification. We propose that epigenetic modification. of a major predisposing gene in somatic tissues could cause differences in disease activity of psoriasis and could account for the often unpredictable clinical course the disease takes.
Birth prevalence study of the apert syndrome
Authors: Cohen M. Michael , Kreiborg Sven , Lammer Edward J. , Cordero José F. , Mastroiacovo Pierpaolo , Erickson J. David , Roeper Peter , Martínez‐Frías Maria Luisa
Published: June 2005

Estimates of the Apert syndrome birth prevalence and the mutation rate are reported for Washington State, Nebraska, Denmark, Italy, Spain, Atlanta, and Northern California. Data were pooled to increase the number of Apert births (n = 57) and produce a more stable birth prevalence estimate. Birth prevalence of the Apert syndrome was calculated to be approximately 15.5/1, 000,000 births, which is twice the rate determined in earlier studies. The major reason appears to be incomplete ascertainment in the earlier studies. The similarity of the point estimates and the narrow bounds of the confidence limits in the present study suggest that the birth prevalence of the Apert syndrome over different populations is fairly uniform. The mutation rate was calculated to be 7.8×10−6 per gene per generation. Apert syndrome accounts for about 4.5% of all cases of craniosynostosis. The mortality rate appears to be increased compared to that experienced in the general population; however, further study of the problem is necessary.
del(18p) syndrome with complex tetralogy of fallot in an infant with 45,X,t(Y;18)(q12;q11.2)
Authors: Kalla S. El , Mathews A. R. , Menon N. S.
Published: June 2005

We report on an infant with multiple congenital anomalies, tetralogy of Fallot, and Karyotype 45,X,t(Y;18)(q12;11.2). The infant's anomalies are consistent with a del(18p) syndrome, except for the exceptional severity of the heart defect.
Glycogen storage disease type III with muscle involvement: Reappraisal of phenotypic variability and prognosis
Authors: Momoi Toru , Sano Hirohiko , Yamanaka Chutaro , Sasaki Hiroshi , Mikawa Haruki
Published: June 2005

A review of the case histories of 19 Japanese patients with enzymatically proven glycogen storage disease (GSD) III who developed muscular symptoms at various ages illustrates the phenotypic variability of this disease. There seem to be 4 subgroups of GSD III with muscle involvement according to the clinical symptoms. The first group of patients is characterized by the childhood onset of muscle weakness and hepatic disorders. The second group of patients develops muscular symptoms in adult years while the liver symptoms start in childhood. The third group includes the patients whose muscle weakness started in adult years long after liver symptoms in childhood had disappeared. The fourth group shows only muscular symptoms as adults without any sign or history of liver dysfunction since childhood. The prognosis for each subgroup seems to be different; however, none of them appears to be better than that for GSD I, as has been suggested previously.
Congenital absence of the vas deferens: Recurrence in a family
Authors: Martin Rick A. , Jones Kenneth Lyons , Downey Earl C.
Published: June 2005

We report on 2 brothers with congenital absence of the vas deferens discovered in childhood during inguinal hernia repairs. The vas is absent unilaterally in one sib and bilaterally in the other. The unusual presentation of inguinal hernias in these children is discussed as well as mechanisms of inheritance and associated risk of renal anomalies.
Charcot‐marie‐tooth neuropathy related to chromosome 1
Authors: Ionasescu Victor V. , Trofatter James , Haines Jonathan L. , Ionasescu Rebecca , Searby Charles
Published: June 2005

One family with documented male‐to‐male transmission of Charcot‐Marie‐Tooth (CMT) neuropathy was studied clinically and by genetic linkage. Patients had progressive distal weakness and atrophy, areflexia, and distal sensory loss, but early onset (before age 3 years) in all 5 cases, and phrenic nerve involvement in the propositus (a 39‐year‐old woman) requiring CPAP ventilator support during the night. Motor‐nerve conduction velocities (MNCVs) were significantly slow, consistent with severe demyelinating neuropathy. Electromyography (EMG) data were normal. Two‐point and multipoint linkage analyses strongly suggested the presence of a CMT gene on chromosome 1q. A maximum multipoint lod score of 2.70 was obtained at MUCI (θ = 0), with the locus order centromere‐MUC1‐SPTA1‐FcγRII‐AT3‐telomere. Multipoint linkage analysis excluded the CMT locus from chromosome 17 markers in this family.
High frequency of congenital adrenal hyperplasia (classic 11β‐hydroxylase deficiency) among Jews from Morocco
Authors: Rösler Ariel , Leiberman Esther , Cohen Tirza
Published: June 2005

Steroid 11β‐hydroxylase deficiency is relatively frequent in Israel among North African Jews. Over a 39‐year period, 38 affected individuals from 25 families were diagnosed. Nineteen families came from Morocco, and in another 2, one parent came from Morocco (80% of all parents). Demographic studies showed that most of their grandparents were born in the region of the Atlas Mountains. In Israel, the overall incidence of the disorder is estimated between 1 in 30,000 to 1 40,000 births, but in offspring of Moroccan Jews the ratio is 1 in 5,000 to 1 in 7,000, with an allele frequency of 1 in 70 to 1 in 84 and a carrier frequency of 1 in 35 to 1 in 42.

The clinical expression in characterized by a wide range of variability in the signs of androgen and mineralocorticoid excess. Virilization in the female ranged from enlarged clitoris in the mildest forms, to markedly hypertrophied clitoris with penile urethra and fused labial‐scrotal folds in the most severe forms. Hypertension causing vascular accidents and death was observed in both severe and mildly virilized patients, whereas masculinized females were sometimes normotensive.

Based on historical evidence, the origin of the ancestors, and the onomastic analysis of the families surnames, we propose that the mutation of 11β‐hydroxylase dificiency in Jews from Morocco may have originated in either the ancient Jewish settlers or the native Berber tribes who lived in the region of the Atlas Mountains in the southern region of Morocco before the destruction of the Second Temple by the Romans, in the year 70 C.E.
Frequency of the common fragile site at Xq27.2 under conditions of thymidylate stress: Implications for cytogenetic diagnosis of the fragile‐X syndrome
Authors: Ramos Feliciano J. , Emanuel Beverly S. , Spinner Nancy B.
Published: June 2005

The distal long arm of the X chromosome contains at least 2 fragile sites, the well known rare site at Xq27.3 (FRAXA), associated with the fragile‐X syndrome, and a common fragile site at Xq27.2 (FRAXD), inducible by high doses of aphidicolin. Lesions at Xq26 have also been reported in lymphocytes of mentally retarded individuals cultured under folate deprivation or thymidylate stress. This study determines the frequency of the fragile site at Xq27.2 and lesions at Xq26 in individuals referred to our laboratory to rule out the fragile‐X syndrome and in control individuals using our routine culture system for the diagnosis of the syndrome. FRAXD was expressed in 1/20 (5%) individuals in each of the study groups, in 1–2% of cells. Lesions at Xq26 were found in 1–2% of the lymphocytes of 5/166 (3%) patients referred for fragile‐X analysis who were FRAXA negative, and in 1% of cells of 1/20 (5%) control individuals. We conclude (1) the fragile site at Xq27.2 can be demonstrated in normal individuals under conditions of thymidylate stress routinely used for cytogenetic diagnosis of the fragile‐X syndrome, (2) this fragile site is present at low levels (1–2%) in all individuals who express it and, therefore, its expression is unlikely to cause false positive diagnoses of the syndrome, (3) lesions at Xq26 are also seen at low levels in lymphocytes of individuals without the syndrome, and (4) accurate differentiation of the rare site at Xq27.3 from other distal Xq fragile sites or lesions will lead to avoidance of unnecessary repeat studies.
Behavioral phenotype of fragile X syndrome: DSM‐III‐R autistic behavior in male children
Authors: Reiss Allan L. , Freund Lisa
Published: June 2005

Comparison of 34 fragile X [fra(X)] male children (age 3–18 years) with 32 IQ‐ and age‐matched, non‐fra(X) male control children was conducted using specific DSM‐III‐R criteria for autism. Statistical analyses supported predictions that fra(X) males show increased dysfunction in peer social play, nonverbal communication (e.g., gaze aversion, gesturing), verbal communication (e.g., rate, volume, word/pharse perseveration), and repetitive motor behaviors (e.g., handflapping, rocking). There was a trend for fra(X) children to show abnormal responsivity to sensory stimuli as well such as oversensitivity to sound and increased mouthing or smelling of objects. The investigation supports the contention that fra(X) males manifest a specific subset of behaviors from the autistic spectrum. Implications for treatment are discussed.