bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoimmune thyroiditis associated with mild “subclinical” hypothyroidism in adults with down syndrome: A comparison of patients with and without manifestations of Alzheimer disease
Authors: Percy Maire E. , Dalton Arthur J. , Markovic Vjerica D. , McLachlan Donald R. Crapper , Gera Edith , Hummel Jocelyn T. , Rusk Ann C. M. , Somerville Martin J. , Andrews David F. , Walfish Paul G.
Published: June 2005

Serum tests of thyroid function were compared in Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD). Relative to control individuals, DS patients had, overall, lower mean total T4 (P = 0.070) and T3 (P = 0.015), higher T3U (P = 0.013) and TSH (P = 0.020), no difference in free T4, and higher thyroid antithyroglobulin (ATA) (P = 0.033) and antimicrosomal autoantibody (AMA) titres (P = 0.0097). Similar trends were apparent in DS males and females, and in DS patients off all drugs. In an analysis of case/control pairs with corrections for age and sex, DS patients with AD manifestations (n = 9) had significantly lower T3 (P = 0.029) and higher AMA (P = 0.043) than paired control individuals, whereas DS patients without AD manifestations (n = 20) had significantly lower T3 (P = 0.013) but higher ATA (P = 0.0065). T3 was significantly lower in the DS patients with AD manifestations than in the unaffected (P = 0.0013). These data suggest that autoimmune thyroiditis associated with a mild “subclinical” form of hypothyroidism is common in adult DS patients and more pronounced in patients with AD manifestations than in those without. This “subclinical” hypothyroidism may contribute to cognitive deficits in ageing DS patients.
New cases of dermoodontodysplasia?
Authors: Pinheiro Marta , Gomes‐de‐Sá‐Filho Floriano Peixoto , Freire‐Maia Newton
Published: June 2005

We report on 2 sisters and one brother with severe dental anomalies, trichodysplasia, onychodysplasia, and slight skin alterations. Four other relatives have only mild dental anomalies. Differential diagnosis includes 3 other ectodermal dysplasias: hypodontia and nail dysgenesis, dermoodontodysplasia, and trichodermodysplasia with dental alterations. Cause is unknown.
Social mechanisms in the population genetics of Tay‐Sachs and other lethal autosomal recessive diseases: A computer simulation model
Authors: McKusick Kathleen B. , Schach Stephen R. , Koeslag Johan H.
Published: June 2005

A computer simulation model was developed to study the effects of various feudal social customs on the incidence of lethal autosomal recessive genes. Populations of 500 individuals were created in which each person was characterized by sibship, genotype, and sex. The numbered sibships were sorted into numerical order. Each individual then sought a mate from 6 or 12 sibships on either side of his or her own sibship. The resulting couples were sorted in order of the husband's sibship number, after which the couples produced children in accordance with the prevailing birth rate. This ordering of sibships made the probability of a gene remaining in one locality higher than the probability of it drifting to distant localities.

A lethal autosomal recessive gene was introduced into populations at a starting carrier rate of 10%. This fell after 20 generations to 2.54 ± 0.17% (SEM) which was significantly less than the 5.00% carrier rate predicted by a deterministic model in which random mating occurred in an infinite population. The excessive loss of the lethal gene was caused by the high incidence of consanguineous marriages and by the occurrence of random inequalities in the distribution of the gene. The avoidance of sib marriages raised the final carrier frequency (3.28 ± 0.19%) as did reproductive compensation (4.33 ± 0.26%). The combination of the incest taboo and reproductive compensation raised the final carrier rate to 5.05 ± 0.28%. It is concluded that the social factors which may have operated over a period of many centuries in the past have had a significant effect on the population genetics of lethal autosomal recessive genes.
Use of a probe for the putative sex determining gene, Zinc finger Y, in the study of patients with ambiguous genitalia and XY gonadal dysgenesis
Authors: Erickson Robert P. , Verga Vera , Dasouki Majed
Published: June 2005

Using reverse genetics, a candidate for the sex determining gene from the Y chromosome has recently been cloned. We have used a DNA probe from this gene to assess the presence of this crucial region of the Y chromosome in patients with sexual ambiguity or gonadal dysgenesis. The DNA from 3 cases of gonadal dysgenesis, one complicated by somatic anomalies and mental retardation, reacted normally with this putative sex determining gene. A patient having a small phallus and pseudovaginal, perineoscrotal hypospadias (PPSH) also had normal Y chromosomal DNA. We hypothesize that the defect in sex determination in all 4 cases is most probably subsequent to the primary sex determining switch.
Short stature, brachydactyly, small ears, and a pattern of minor anomalies in brother and sister born to consanguineous parents: A Hitherto Unreported syndrome?
Authors: Schinzel Albert , Bernasconi Sergio
Published: June 2005

A 13‐year‐old boy and his 28‐year‐old sister had short stature, obesity, and a pattern of minor anomalies including a sloping, narrow forehead; small ears; a narrow nose with prominent bridge and long septum; short upper lip; receding mandible; and short limbs with brachydactyly and clinodactyly of little fingers. The boy also had hypoplastic external genitalia and elevated FSH. Both are of normal intelligence. There is remote consanguinity of the (normal) parents. The 2 sibs probably represent a hitherto un‐recognized syndrome of possibly autosomal recessive inheritance.
Complicated hereditary spastic paraparesis with cerebral white matter lesions
Authors: Gutmann David H. , Fischbeck Kenneth H. , Kamholz John
Published: June 2005

A family is described with 5 males in a single generation affected with a previously undescribed complicated form of hereditary spastic paraparesis (HSP). The disease is characterized by speech difficulties, lower limb spasticity and hyper‐reflexia, mental retardation, cerebellar ataxia, and tremor. The disease starts in the first decade of life and progresses for 3 to 6 years before stabilizing. Magnetic resonance imaging (MRI) of the brain demonstrates bilateral posterior peri‐ventricular white matter lesions. Visual evoked responses are markedly prolonged, but electromyography (EMG) and nerve conduction velocity studies are normal. Three of the 4 living affected members of this pedigree exhibit red‐green color vision defects. The presentation of a new complicated hereditary spastic paraparesis syndrome in this pedigree extends our understanding of the variability and heterogeneity of this syndrome and suggests an approach for the evaluation of similar families in future genetic studies.
An unusual type of acrocephalosyndactyly with bilateral parietooccipital “encephalocele”, micropenis, and severe mental retardation
Authors: Lorenz Peter , Rupprecht Edgar , Tellkamp Harald
Published: June 2005

Here we report on a 2 year 3‐month‐old boy with acrocephalosyndactyly, a bilateral parietooccipital “encephalocele”, micropenis, and severe mental retardation. To our knowledge there are no other reports of similarly affected patients in the literature.
Restrictive dermopathy with distinct morphological abnormalities
Authors: van Hoestenberghe Marie‐Rose , Legius Eric , Vandevoorde Wim , Eykens Albert , Jaeken Jaak , Eggermont Ephrem , Devos Rita , De Wolf‐Peeters Chris , Fryns Jean‐Pierre
Published: June 2005

A newborn child is described with the fetal hypokinesia sequence as a consequence of a restrictive dermopathy. Remarkable findings in this infant were neonatal teeth and survival till age 4 months. Ultrastructural examination of the skin showed thin epidermis and absence of elastic fibres.
Overo lethal white foal syndrome: Equine model of aganglionic megacolon (Hirschsprung disease)
Authors: McCabe Linda , Griffin Lisa D. , Kinzer Andrew , Chandler Marge , Beckwith J. Bruce , McCabe Edward R. B.
Published: June 2005

The lethal white foal syndrome (LWFS) is a congenital abnormality of overo spotted horses which is a model for human aganglionic megacolon or Hirschsprung disease. Foals with LWFS have an all white, or nearly all white, coat. They also present clinically with an intestinal obstruction that proves fatal within the first few days of life. The LWFS involves both melanocytes and intestinal ganglion cells, and appears to result from a genetic defect involving neural crest cells. This report describes pathologic studies of two recent cases of LWFS. Two different hypothetical models of inheritance of LWFS are presented and discussed.
Acheiropodia: Report on four new Brazilian patients
Authors: Fett‐Conte A. C. , Richieri‐Costa A.
Published: June 2005

We report on 4 new patients with acheiropodia (“the handless and footless families of Brazil”). This autosomal recessive condition involves all 4 limbs with a well‐defined pattern of defects. Two of the patients described here had a small bone fragment in the upper stumps (Bohomoletz bone), an uncommon finding in acheiropodia.
Urinary tract anomalies associated with congenital diaphragmatic defects
Authors: Siebert Joseph R. , Benjamin Denis R. , Juul Sandra , Glick Philip L.
Published: June 2005

Anomalies of the urinary tract occur in some 13–27% of infants with congenital posterolateral diaphragmatic defect (CDD) and are often severe (renal agenesis, dysplasia, hypoplasia, or hydronephrosis). To test the hypothesis that urinary and diaphragmatic anomalies share elements of pathogenesis, we reviewed 60 autopsy cases of CDD studied at our institution. Sixteen patients (27%) manifested anomalies of the urinary tract: 12 had markedly altered kidneys, 8 of which were unilateral and ipsilateral to the diaphragmatic defect. Among 27 patients free of gross urinary tract anomalies, kidney weights formed a skewed distribution, with most values above published norms for body weight; by analysis of covariance, kidney weight (as a function of body weight) was significantly greater in CDD than in a control population of infants free of chronic illnesses and congenital anomalies who died suddenly and unexpectedly. Differences in glomerular number and diameter could not be identified between the latter groups. In 71% of patients with isolated left CDD, the left kidney was heavier than the right, a reversal of the usual condition in infancy. These findings demonstrate that both marked and subtle changes of the urinary tract in CDD are generally ipsilateral to the diaphragmatic defect and suggest that the pathogenetic mechanisms responsible for urinary and diaphragmatic anomalies may overlap topographically. Aberrant morphogenesis within a developmental field or fields is one explanation for this.
Segregation analysis of the X‐chromosome in a family with rett syndrome in two generations
Authors: Anvret Maria , Wahlström Jan , Skogsberg Per , Hagberg Bengt
Published: June 2005

We report on the first family in which Rett syndrome (RTS) appeared in two consecutive generations. The index case is a 12‐year‐old girl (classical RTS); her maternal aunt, age 44 years, has mild RTS. Clinically, the family illustrates the wide phenotypic variability between cases, particularly in severity of neurological manifestations. We have analyzed the short arm of the X‐chromosome of the family with gene technology. This did not uncover any genetic marker for diagnosis, but it did suggest how the syndrome might have segregated in the family. A cytogenetic analysis gave no information about chromosome abnormalities.
Oral motor dysfunction in individuals at risk of huntington disease
Authors: Coleman Ralph , Anderson Daryl , Lovrien Everett
Published: June 2005

We studied the performance of 34 as yet undiagnosed individuals known to be at risk of Huntington disease (HD), on a maximum‐effort oral‐motor task. Results were compared with those from a normal control group matched for age and sex. The at‐risk‐of‐HD population was significantly slower overall than the normal group on all 5 of the oral‐motor tasks. This is interpreted as indicating that the presence of HD in the one half of the population expected to have it, affected the group's overall performance even though the clinical signs associated with HD had not yet appeared. In addition, rankings of repetition rates in both groups indicate that approximately one half of the at‐risk population was consistently associated with the slowest 25% of the combined groups forming, in essence, a subgroup of the at‐risk population. The performance of the other one half of the at‐risk group did not differ systematically from that of the normal control persons. Minimal repetition rates were identified on each oral‐motor task that may serve as early clinical “indicators” for the presence of HD in the population known to be at risk.
De novo (15;21) unbalanced translocation of paternal origin in a girl with prader‐willi syndrome
Authors: Cuoco C. , Bicocchi M. P. , Granata D. , Mezzano P. , Serra G.
Published: June 2005

We describe a 3‐month‐old girl with Prader‐Willi syndrome and a de novo unbalanced karyotype 45,XX,t(15;21)(q13;q22.3). This rearrangement, resulting in monosomy for the pericentromeric region of chromosome 15 and a virtual monosomy for the 21q distal band, had a paternal origin as demonstrated by Q and NOR staining.
Dandy‐walker variant malformation, spastic paraplegia, and mental retardation in two sibs
Authors: Stoll Claude , Huber Christian , Alembik Yves , Terrade Eliette , Maitrot Daniel
Published: June 2005

Two sibs, a boy and a girl, had both hypo‐plasia of the cerebellar hemispheres and partial agenesis of the cerebellar vermis with normal communication between the fourth ventricle and arachnoid spaces, i.e., the manifestations of the Dandy‐Walker variant malformation associated with agenesis of the corpus callosum.

Both sibs were mentally retarded and had spastic paraplegia. The occurrence of a distinct and similar pattern of congenital anomalies in sibs born to healthy parents points toward a “new” syndrome caused by the homozygous state of an autosomal recessive gene. Prenatal ultrasonographic diagnosis is possible at least for the more severe form of the brain anomalies.
Limb reduction defects and renal dysplasia: Confirmation of a new, apparently lethal, autosomal recessive MCA syndrome
Authors: Schrander‐Stumpel Constance , de Die‐Smulders Christine , Fryns Jean Pierre , da Costa Joost , Bouckaert Peter
Published: June 2005

We report on 2 sibs, a male and a female, who died shortly after birth from respiratory failure. They combined growth retardation with a Potter‐like face, complete phocomelia of the upper limbs, rib anomalies (mainly severe hypoplasia of the 6 upper ribs), renal dysplasia, and external genital abnormalities. We hypothesize that these cases represent evidence for the existence of the “new syndrome” described by Ulbright et al. (Am J Med Genet 17:667–668, 1984). This syndrome appears lethal because of the severe renal dysplasia that causes oligohydramnios and pulmonary hypoplasia. Its mode of inheritance seems to be autosomal recessive.
Characterization of deletions in the dystrophin gene giving mild phenotypes
Authors: Love Donald R. , Flint Tracey J. , Marsden Rosalind F. , Bloomfield Jennifer F. , Daniels Rachael J. , Forrest Susan M. , Gabrielli Orazio , Giorgi Pierluigi , Novelli Giuseppe , Davies Kay E.
Published: June 2005

We have characterized deletions of the dystrophin gene in patients suffering from relatively mild muscular dystrophy. Our data show that most of the Becker muscular dystrophy (BMD) patients have intragenic deletions which leave the protein reading frame in phase. Remarkably, large deletions of the region corresponding to the central triple helical repeats in the protein can result in an exceptionally mild phenotype. Three brothers suffering from BMD, glycerol kinase deficiency, and adrenal hypoplasia possess a deletion at the 3′ end of the gene. They also display developmental delay. Thus the 3′ processing of the gene must be necessary for the correct function of the dystrophin molecule.
An animal model of the marfan syndrome
Authors: Besser Thomas E. , Potter Kathleen A. , Bryan Gary M. , Knowlen Grant G.
Published: June 2005

A congenital syndrome of long, thin limbs, severe joint and tendon laxity, micro‐spherophakia, ectopia lentis, heart murmurs and aortic dilatation was identified in 7 calves. All affected calves were sired by a single phenotypically normal bull suspected of germline mosaicism for a new mutation resulting in this disease. One of the calves subsequently died with ruptured aorta at age 16 months. Histopathologic and electron microscopic studies of the aortic media of affected calves demonstrated disorganized elastin and narrowed elastic lamina separated by widened spaces. This bovine disease provides a unique animal model of the human Marfan syndrome. A herd of cattle with this disease is being developed for further studies.
Rearrangement of chromosome 15 in the region q11.2→q12 in an individual with obesity syndrome and her normal mother
Authors: Shohat M. , Shohat T. , Rimoin D. L. , Mohandas T. , Heckenlively J. , Magenis R. E. , Davidson M. B. , Korenberg J. R.
Published: June 2005

Rearrangements of the proximal long arm of chromosome 15 have been found in most patients with the Prader‐Willi syndrome (PWS) and in some with Angelman syndrome. We present an individual with syndromic obesity and her normal mother, who both have an abnormal chromosome 15. The proposita is a 26‐year‐old woman with marked obesity, acanthosis nigricans, short fingers, and severe cone degeneration of the retina. She has high plasma insulin levels, hypothyroidism, and an empty sella on CT scan. High‐resolution chromosome banding demonstrated an increase in band 15q12. Further analysis showed the same abnormal 15 in her normal mother but not in her normal sister. This case and recent reports in the literature indicate that duplications of chromosome 15q in the PWS region may be associated with a syndrome of obesity, acanthosis nigricans, empty sella, and rodcore dystrophy as well as with a normal phenotype. Whether normal individuals with such a duplication carry increased risk of having offspring with an obesity syndrome is yet to be determined.
Chondrodysplasia punctata, tibia‐metacarpal (MT) type
Authors: Rittler M. , Menger H. , Spranger J.
Published: June 2005

We describe 7 patients with a new form of chondrodysplasia punctata. Its principal clinical manifestations are flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn infant are discrete calcific stippling, coronal clefts of vertebral bodies, short tibiae, and shortness of the 2nd and 3rd metacarpal bones. Radiologic findings in the older child include shortness of tibiae and the 3rd and 4th metacarpals.
GAPO syndrome (McKusick 23074)—A connective tissue disorder: Report on two affected sibs and on the pathologic findings in the older
Authors: Wajntal Anita , Koiffmann Célia P. , Mendonça Berenice B. , Epps‐Quaglia Dorina , Sotto Myriam Nacagami , Rati Patrícia B. M. , Opitz John M.
Published: June 2005

GAPO syndrome was described in 12 patients from 7 families. Constant manifestations include dwarfism, alopecia, pseudoanodontia, and a peculiar, “geriatric” facial appearance. We describe the autopsy findings and all available clinical data on one deceased patient and his living affected sister, previously reported as short abstracts (Epps et al.: Cienc Cult 29(Suppl):740, 1977; Wajntal et al.: Cienc Cult 34(Suppl):705, 1982). Both had the characteristic anomalies of this syndrome but optic atrophy was absent; instead, they had glaucoma and keratoconus; hypogonadism was present in both patients. Biopsy and autopsy findings show that the GAPO syndrome is a dyshistogenetic sequence due to accumulation of extracellular material and thus should be called GAPO dysplasia. We suggest that the basic defect in this autosomal recessive disorder is possibly related to a lack of breakdown of the extracellular components, perhaps due to an enzyme deficiency involved in the metabolism of extracellular matrix.
Central nervous system malformations in the CHARGE association
Authors: Lin Angela E. , Siebert Joseph R. , Graham John M.
Published: June 2005

Of 144 patients with the CHARGE association (literature 136, new patients 8), 47 (33%) had either a postmortem examination (30) or computerized axial tomography scan (17) of the head. Twenty‐six of 47 (55%) had definite central nervous system (CNS) malformations: arhinencephaly, with or without other defects (11), holoprosencephaly (2), holoprosencephaly with arhinencephaly (1), other forebrain defects (3), hindbrain defects (3), or other defects (6). The presence of CNS malformation was most strongly associated with choanal atresia. This review demonstrates a predominance of forebrain anomalies, particularly arhinencephaly and holoprosencephaly, which may provide a clue to the mechanism of abnormal morphogenesis involved in CHARGE association.
Multiple endocrine neoplasia: How many syndromes?
Authors: Schimke R. Neil
Published: June 2005

The phrase multiple endocrine neoplasia (MEN) generally denotes an association of tumors so specific as to constitute a syndrome. Three well‐recognized such syndromes exist. All are autosomal dominant traits and all have been tentatively mapped to specific chromosomes. Other purported endocrine tumor syndromes have been suggested either as new entities or as subtypes of the existing MEN syndromes. The evidence in favor of these contentions is examined critically. Only one “new” association. That of pheochro‐mocytomas and islet cell tumors, seems reasonable, and even in this setting, some relatives have had manifestations of von Hippel‐Lindau syndrome. There is no compelling reason why such conditions as von Hippel‐Lindau syndrome, peripheral neuro‐fibromatosis, McCune‐Albright syndrome, and others should be reclassified as MEN syndromes, although awareness of their collective endocrine abnormalities is clinically important.
Five children with del (2)(q31q33) and one individual with dup (2)(q31q33) from a single family: Review of brain, cardiac, and limb malformations
Authors: Ramer Jeanette C. , Mowrey Philip N. , Robins David B. , Ligato Saverio , Towfighi Javad , Ladda Roger L.
Published: June 2005

Five matings to a dir ins (6;2)(q16aq31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre‐ and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of over‐lapping regions of 2q.
Homozygous achondroplasia: Morphologic and biochemical study of cartilage
Authors: Stanescu Ritta , Stanescu Victor , Maroteaux Pierre
Published: June 2005

We have performed histochemical, immunohistochemical, electron microscopic, and biochemical studies on the upper tibial cartilage from a case of homozygous achondroplasia.

The growth zone was narrow and disorganized. Columnization was absent except for a few areas with short rows of cells. Hypertrophy was reduced to scattered clusters of cells. The provisional calcification was patchy and primary trabeculae were thick and irregularly arranged. Islands of fibrous or fibrocartilagineous tissue were found along the growth zone. The matrix did not stain with safranin O and lacked metachromasia, except for pericellular rims around the hypertrophic cell clusters. Staining with antibodies against the large proteoglycan monomers and chondroitin‐4‐sulfate was weakly positive. Electron microscopic examination showed that only a few cells had degenerative signs. In most areas of the matrix, proteoglycan granules were absent. Areas with dense collagen fibers were seen.

In contrast to the growth zone, the cartilage of the remaining epiphyses had normal histochemical, immunohistochemical, and electron microscopic appearance.

The large proteoglycan monomers had a normal composition and hydrodynamic size. Type II and XI collagen, pepsin fragments of type IX collagen, and several noncollagenous proteins extracted from cartilage had a normal electrophoretic migration.

It is suggested that a mutation affecting a matrix component or a regulatory pathway present only or predominantly in the growth area of the chondroepiphysis might explain the findings.
Congenital heart disease and Robinow syndrome: Coincidence or an additional component of the syndrome?
Authors: Webber Steven A. , Wargowski David S. , Chitayat David , Sandor George G. S.
Published: June 2005

We report on a girl with Robinow syndrome and pulmonary atresia with ventricular septal defect (VSD). Seven cases of Robinow syndrome with congenital heart defect (CHD) have now been described, 5 of whom had stenosis or atresia of the pulmonic valve. This suggests that CHD, especially right ventricular outlow obstruction, may be a component manifestation of this syndrome in some cases. Since early recognition of this type of heart lesion can minimize morbidity by facilitating optimal surgical therapy, thorough cardiac evaluation of all patients with Robinow syndrome seems warranted.
Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6
Authors: Weissbecker K. A. , Durner M. , Janz D. , Scaramelli A. , Sparkes R. S. , Spence M. A.
Published: June 2005

Juvenile myoclonic epilepsy (JME) is a generalized, non‐progressive epilepsy characterized by an adolescent onset of sudden, involuntary myoclonic jerks. Greenberg et al. (American Journal of Medical Genetics 31:185–192, 1988b; Cytogenetics and Cell Genetics 51:1008, 1989b) reported tight linkage of a JME locus to the HLA region of chromosome 6p. We confirm this linkage assignment, although at a larger recombination fraction than previously reported.

Twenty‐three, mostly nuclear, families were ascertained through a JME proband. The affected status of relatives of the probands was assigned by 4 different clinical criteria, and separate analyses were done assuming an autosomal dominant model with 90% penetrance and an autosomal recessive model with full penetrance. A linear age‐of‐onset correction with maximum penetrance at age 20 years was incorporated into the analyses. The maximum lod score obtained was 3.11 at Θm = 0.001, Θf = 0.20, assuming autosomal dominant inheritance and using the second definition of the disease phenotype. There was strong support for linkage using the other phenotype definitions and the autosomal dominant model, although the lod scores did not exceed 3.0. There was also support for linkage of a JME locus to this region under the autosomal recessive model, although the results varied depending upon the definition of the disease phenotype. There was no significant evidence for linkage heterogeneity.
VATER and hydrocephalus: Distinct syndrome?
Authors: Iafolla A. Kimberly , McConkie‐Rosell Allyn , Chen Yuan Tsong
Published: June 2005

VACTERL association with hydrocephalus is rarely reported, and is thought to be an autosomal recessive uniformly lethal disorder distinct from the VATER association. We have observed 3 patients in a 12‐month period with hydrocephalus due to aqueductal stenosis, in addition to vertebral anomalies (3/3), anal anomalies (3/3), cardiac anomalies (3/3), tracheoesophageal fistula (1/3), renal anomalies (3/3), limb anomalies (3/3), single umbilical artery (2/3), hypospadias (1/3), and cryptorchidism (1/2). Chromosomes were normal in all cases. Although one patient died in the neonatal period due to respiratory failure, 2 have survived (30 months and 19 months) with good neurological outcome following early neurosurgical treatment. Although delayed in motor development, both are interactive, social, and continue to make developmental progress. Appropriate surgical treatment, including early ventriculoperitoneal shunting, allowed for the survival of 2 patients with an unexpectedly good outcome. Our experience suggests that the extremely poor prognosis previously ascribed is not universal. We caution against labeling this syndrome as a uniformly lethal, developmentally devastating disorder.
Congenital gastric teratoma in Wiedemann‐Beckwith syndrome
Authors: Falik‐Borenstein Tzipora C. , Korenberg Julie R. , Davos Irene , Platt Lawrence D. , Gans Stephen , Goodman Barbara , Schreck Rhona , Graham John M.
Published: June 2005

Wiedemann‐Beckwith syndrome (WBS) may be associated with abdominal tumors, including Wilms tumor, adrenocortical carcinoma, hepatoblastoma, gonadoblastoma, rhabdomyosarcoma, and neuroblastoma. We report on a newborn infant with WBS and a congenital teratoma of the stomach. This is the sole report of any teratoma being associated with WBS and also the first report of a tumor present at birth and visible prenatally in WBS. At birth this infant boy had the diagnostic findings of WBS with macroglossia, ear lobule creases and pits, nevus flammeus, and omphalocele, and an abdominal mass. Abnormalities were detected prenatally when ultrasound examination showed placental overgrowth, polyhydramnios, omphalocele, and posterior abdominal calcifications. Resection of the mass and partial gastrectomy were performed at age 10 days; histologic study showed an immature grade‐II teratoma containing a mixture of mature and immature tissues from all germ layers. Results of cytogenetic studies of blood and teratoma were normal (46,XY). This congenital gastric teratoma in a newborn boy with classical WBS may represent either a tumor or an included twin. We discuss its implications for the association of WBS with neoplasia and monozygotic (MZ) twinning, review various neoplasias associated with WBS, and consider pathogenetic mechanisms.
Possible common pathogenetic mechanisms for Poland sequence and Adams‐Oliver syndrome
Authors: Der Kaloustian Vazken M. , Hoyme H. Eugene , Hogg Heidi , Entin Martin A. , Guttmacher Alan E.
Published: June 2005

We report on 2 families having members affected with the Poland sequence and Adams‐Oliver syndrome. In the first family, a 5‐month‐old boy presented with Adams‐Oliver syndrome; his mother had Poland sequence. In the second family, a 12‐year‐old boy and his mother presented with findings suggestive of Adams‐Oliver syndrome and Poland sequence. This suggests that the same genetic predisposition may result in either or both conditions.
Polyasplenia, caudal deficiency, and agenesis of the corpus callosum
Authors: Rodríguez José Ignacio , Palacios José , Omeñaca Félix , Lorente Marién
Published: June 2005

Fullana et al. [Am J Med Genet (suppl. 2): 23–29, 1986] reported on 2 sibs with an autosomal recessive syndrome of caudal deficiency and polyasplenia anomalies. We report on a similar patient in which agenesis of the corpus callosum (ACC) was also found. Such an association has not been reported previously. This finding of ACC is to be interpreted as another midline anomaly rather than as a causally independent malformation.
The Rapp–Hodgkin syndrome
Authors: Breslau‐Siderius E. J. , Lavrijsen A. P. M. , Otten F. W. A. , van der Schroeff J. G. , Swart J. G. N.
Published: June 2005

We report on a family with the Rapp‐Hodgkin ectodermal dysplasia syndrome. Four affected family members are described and a review of the literature is given.
Computerized approach to X‐linked mental retardation syndromes
Authors: Arena J. Fernando , Lubs Herbert A.
Published: June 2005

Photographs of normal and abnormal relatives with X‐linked mental retardation (XLMR) and clinical data are combined in a Macintosh II computer system to provide an objective and versatile means of evaluating developmental abnormalities. The system includes a flatbed scanner for the entry of photographs and text, additional memory to enhance resolution of photographs, and several programs which facilitate searches for keywords. The primary advantages of the system include an easy interaction between descriptive words and photographs, and rapid comparison of whole faces and specific traits from many individuals. Information within families and between disorders can easily be compared in coded or uncoded fashion. Data from the 34 currently described syndromes emerging from the category of “non‐specific XLMR” are being used to develop and test this approach. Neither standard photographs nor most computerized diagnostic systems permit this flexibility. Ultimately, this approach will provide a valuable diagnostic and teaching aid.
Gene for non‐specific X‐linked mental retardation maps in the pericentromeric region
Authors: Samanns Christine , Albrecht Regine , Neugebauer Meinhard , Neri Giovanni , Gal Andreas
Published: June 2005

Linkage analysis was carried out in a large four‐generation German family segregating for non‐specific X‐linked mental retardation. Affected males have moderate intellectual handicap. Speech delay, deviant behaviour, and hyperactivity have also been reported. Head circumference and testicular volumes are normal. Cytogenetic analysis failed to show evidence for fragile site or structural abnormality of the X chromosome. None of the obligatory carriers shows any clinical symptoms. Close linkage without recombination (lod scores 1.74 to 2.05) has been found between the disease locus (MRX1) and the polymorphic DNA loci DXS7 (Xp11.4‐p11.3), MAOA(Xp11.3–p11.23), DXS255(Xp11.22), and DXS159 (Xq12) suggesting that the gene responsible for the disease in this family maps in the pericentromeric region of the X chromosome. Linkage data obtained with the flanking marker loci OTC (Xp21.1) and DXS95 (Xq21.2–q21.3) also were compatible with this localization of the MRX1 gene. Close linkage to loci from Xp22, Xq22, Xq24–25, or Xq28 could be excluded.
X‐linked mental retardation with marfanoid habitus: First report of four Italian patients
Authors: Lalatta F. , Livini E. , Selicorni A. , Briscioli V. , Vita A. , Lugo F. , Zollino M. , Gurrieri F. , Neri G.
Published: June 2005

We report on 4 new cases of mildly retarded patients with marfanoid habitus and a characteristic constellation of minor anomalies. These patients, although sporadic, are likely to be affected by the same X‐linked type of mental retardation described by Lujan et al. (American Journal of Medical Genetics 17:311–322,1984) and more recently by Fryns and Buttiens (American Journal of Medical Genetics 28:267–274, 1987).

The similar psychiatric history in 2 of our patients suggests that psychotic behaviour could be an additional manifestation, previously unrecognized in this condition.

Late diagnosis of this relatively new syndrome in all our patients confirms the difficulty of the nosologic definition of mentally retarded individuals on clinical grounds alone. On the other hand, the Lujan‐Fryns syndrome appears to be more common than one would have thought.
Simpson‐Golabi‐Behmel syndrome with severe cardiac arrhythmias
Authors: König Rainer , Fuchs Sigrun , Kern Christoph , Langenbeck Ulrich
Published: June 2005

We report on a family with 2 affected males with the X‐linked Simpson‐Golabi‐Behmel (SGB) syndrome. The propositus was a 33‐year‐old man with pre‐ and postnatal overgrowth, “coarse” face with hypertelorism, broad nose, wide mouth, malposition of teeth, submucous cleft, accessory nipples, broad hands with hypoplastic index finger nails, and operated left postaxial hexadactyly. From the age of 26 years he suffered from severe tachyarrhythmias, requiring recurrent defibrillations. The brother of the propositus was macrosomic at birth and had a similar facial appearance. In addition he had a pyloric stenosis and a 3/6 systolic murmur. He died at age 4 months. Cardiac defects and conduction disturbances are major components of the SBG syndrome and can be responsible for death in early infancy and perhaps for cardiac arrest in the adult.
Anthropometric comparison of mentally retarded males with and without the fragile X syndrome
Authors: Butler Merlin G. , Allen G. Andrew , Haynes Judy L. , Singh Dharmdeo N. , Watson Michael S. , Breg W. Roy
Published: June 2005

An anthropometric survey of 41 variables (weight, height, 10 linear, 4 breadth, 22 craniofacial, 2 skinfold, and testicular volume), including multivariate discriminant analysis, was undertaken on 110 mentally retarded males (39 with and 71 without the fra(X) syndrome). The mean Z scores of the fra(X) syndrome males fell between ‐ 2.00 and 8.38 for bizygomatic diameter and testicular volume, respectively, and the range of the mean Z scores of the non‐fra(X) males was from ‐ 2.64 to 2.26 for hand breadth and testicular volume, respectively. There was a statistically significant difference (P < .05) between fra(X) and non‐fra(X) males for 18 measurements (weight, height, 7 linear, 2 breadth, 5 craniofacial, 1 skinfold, and testicular volume), with the greater measurements (excluding bizygomatic diameter) found in fra(X) males. Sitting height, knee‐buttock length, middle finger length, and hand length were negatively correlated (P < .05) with age, whereas bizygomatic diameter, ear length, and ear width were positively correlated (P < .05) with age and head circumference, head length, and outer canthal distance were positively correlated (P < .05) with fra(X) chromosome expression in the fra(X) males. Triceps and subscapular skinfold thicknesses were negatively correlated (P < .05) with age, whereas ankle breadth, ear length, ear width, and nose length were positively correlated (P < .05) in the non‐fra(X) males. Discriminant analysis of 34 fra(X) and 71 non‐fra(X) males resulted in a discriminant function based on 6 of 17 anthropometric variables and age. In the discriminant analysis, patients with the fra(X) syndrome were distinguished from mentally retarded males without the fra(X) syndrome at an overall correct classification rate of 97.1% in our sample. The 6 anthropometric variables in the discriminant function were the Z scores representing testicular volume, ear width, head breadth, bizygomatic diameter, hand breadth, and hand length. Additional research is needed to test the usefulness of these variables in screening mentally retarded males for the fra(X) syndrome.
Molecular characterization of a DNA probe, U6.2, located close to the fragile X locus
Authors: Pergolizzi Robert , Brown W. Ted , Goonewardena Ponmani , Bhan Romal , Dobkin Carl , Dahl Niklas , Pettersson Ulf
Published: June 2005

A new DNA probe, U6.2, defining locus DXS304, was recently shown to be closely linked to the fragile X locus (FRAXA). It is polymorphic with a number of different enzymes, all of which are in complete linkage disequilibrium, which suggests an insertion/deletion type of polymorphism. Using the method of Sanger, we have sequenced 1,102 bp of the cloned U6.2 fragment. Analysis of the sequence showed there was a long direct repeat of 121 bp and two long inverted repeats. The first was 19 bp long, and the second was a palindromic invert of 20 bp. Such repeats could promote recombination in this region and could have been involved in the suggested insertion/deletion event that created the polymorphism detected at locus DXS304. Long fragments were observed using pulsed field gel electrophoresis (PFGE), but no length variations were seen. The sequence of U6.2 will be useful in developing a polymerase chain reaction (PCR) based assay for the restriction fragment length polymorphism (RFLP) detected at locus DXS304 which should assist with carrier detection and prenatal diagnosis of the fragile X syndrome.
Improved prenatal detection of fra(X)(q27.3): Methods for prevention of false negatives in chorionic villus and amniotic fluid cell cultures
Authors: Jenkins Edmund C. , Krawczun Michael S. , Stark‐Houck Sandra L. , Duncan Charlotte J. , Kunaporn Suphat , Gu Hong , Schwartz‐Richstein Carol , Howard‐Peebles Patricia N. , Gross Anne , Sherman Stephanie L. , Brown W. Ted
Published: June 2005

The reliable detection of fra(X)(q27.3) in prenatal samples is important for providing genetic counseling. We have identified 5 new cases of prenatal fragile X [fra(X)] detection in 3 chorionic villus sample (CVS) and 2 amniotic fluid (AF) cell cultures. In 4 of the 5 cases, either excess thymidine (THY) or a combination of THY and 5‐fluorodeoxyuridine (FUdR) was clearly superior to FUdR alone as fra(X) inducers. Amniocytes from one case were cultured only in RPMI‐1640 and later exposed to FUdR or THY separately. They showed only 2% fra(X) while parallel cultures initiated in Chang medium and incubated in RPMI for at least 7 days (recovery) before fra(X) induction exhibited strikingly increased fra(X) frequencies. Chang medium alone will not allow fra(X) induction in AF (Jenkins EC, Brown WT [1986]: “Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment.” New York: Plenum Press, pp 185–204). Now, using CVS cells, we report that only 1% and 0% fra(X) were detected using FUdR or THY in cells cultured in RPMI for 4 days after removal from Chang medium. Cells with 7 days “recovery” in RPMI exhibited increases from 2 to 6%. Therefore, we have found that Chang medium is very helpful when the appropriate recovery time in another medium is allowed before fra(X) induction. Some false negative reports can be attributed to: induction in Chang medium alone; lack of sufficient recovery time after initiating cells in Chang before induction; and unavailability of the excess THY fra(X) induction system. In conclusion, 1) multiple induction systems, including a combination of FUdR/THY, and 2) initial culture of cells in Chang medium with more than a 4 day recovery period in RPMI or another appropriate medium, enhance optimal conditions for prenatal fra(X) detection. These modifications should reduce the possibility of false negatives thereby improving the reliability of prenatal fra(X) detection.
Effects of age and communication level on eye contact in fragile X males and non‐fragile X autistic males
Authors: Cohen Ira L. , Vietze Peter M. , Sudhalter Vicki , Jenkins Edmund C. , Brown W. Ted
Published: June 2005

Dyadic social gaze and eye contact were examined in fragile X [fra(X)] males and in non‐fra(X) autistic males as a function of age and level of communicative ability. Lag sequential analysis showed that responsive eye contact was highly correlated with age and communicative ability in non‐fra(X) autistic males but not in fra(X) males. Older, more communicative non‐fra(X) autistic males exhibited more responsive eye contact than their fra(X) cohorts. Implications of these observations for theory and intervention are discussed.
Cognitive profiles of the carrier fragile X woman
Authors: Brainard Sharon S. , Schreiner Rebecca A. , Hagerman Randi J.
Published: June 2005

Cognitive deficits in females with fragile X [fra(X)] syndrome have been reported, but studies have rarely focused on women with normal intelligence, nor have they separated fra(X)‐negative carriers from fra(X)‐positive carriers. Questions specifically addressed here are: (1) is the degree of fragility predictive of IQ? (2) are cognitive patterns consistent across fragility levels? and (3) do consistent individual profiles exist? These questions were addressed with the help of 74 heterozygous women, 38 of whom were fra(X)‐negative carriers. All women completed the WAISR, and full‐scale IQ was normally distributed (mean = 99.65). A strong inverse relationship between IQ and fragility levels was found. Also, the group of fra(X)‐positive women had a significantly different subtest pattern from that of the fra(X)‐negative women. However, when results were analyzed individually, no consistent patterns emerged. The cognitive performance of fra(X)‐negative carriers has probably been underestimated due to the lack of differentiation between positive and negative carrier females in previous studies. These women appear to be cognitively unimpaired and should be considered separately from fra(X)‐positive women. Since consistent WAIS‐R patterns are not observable on an individual basis, their use as a diagnostic/predictive tool appears to be inappropriate.
Two different phenotypes of fetuses with chromosomal triploidy: Correlation with parental origin of the extra haploid set
Authors: McFadden D. E. , Kalousek D. K.
Published: June 2005

Triploidy is a condition in which there is over‐representation of one parental genome. Recent work in experimental mouse embryogenesis suggests that the parental origin of the extra genome in triploidy may have specific effects on both embryonic/fetal phenotype and placental development due to an “imprinting” effect. We studied 19 human triploid fetuses and discerned 2 distinct fetal phenotypes, as well as the previously described placental phenotypes, which correlate with the parental origin of the extra haploid set. Although these findings suggest that in human triploids the parental origin of the extra haploid set is important in determination of both fetal and placental phenotype it is not clear to what degree nlacental development and function affect the resultant fetal phenotype.
Digeorge anomaly in an infant with deletion of chromosome 22 and dup(9p) due to adjacent type II disjunction
Authors: El‐Fouly Mohamed H. , Higgins James V. , Kapur Saroj , Sankey Beverly J. , Matisoff David N. , Costa‐Fox Maria
Published: June 2005

A term white girl presented with low birth weight, minor anomalies, and congenital heart defects. The infant had microcephaly, upslanting palpebral fissures, prominent nasal bridge, short philtrum, thin upper lip vermilion, down‐turned corners of the mouth, receding mandible, and short broad neck. The hands showed proximal placement of the thumbs, bilateral clinodactyly of the index finger, and bilateral transverse crease. Both hands were clenched, with the index finger overlapping the third finger and the fifth finger overlapping the fourth. There was also talipes calcaneo‐valgus, bilateral dorsifiexion of the metatarsophalangeal joints, flexion of the metatarsophalangeal joints, and hypoplasia of all nails. The patient's karyotype was 46,XX,−22,+der(9)t(9;22)(q21.13;q12.1)mat; the mother had the balanced translocation 46,XX,t(9;22)(9pter → 9q21.13::22q12.1 → 22qter;22pter → 22q12.1::9q21.13 → 9qter). The infant died at age 10 days, and the autopsy showed absent thyroid isthmus and rudimentary thymus, with one small ectopic parathyroid attached to it. The lungs were hypoplastic, with abnormal lobation. The cardiac anomalies included truncus arteriosus, truncal valve stenosis, single carotid trunk, subclavian arteries arising from the distal part of the aortic arch, atrial and ventricular septal defects, right ventricular hypertrophy, and a hypoplastic left pulmonary artery. Also, multiple small accessory spleens were present in addition to a normal‐sized spleen. This case combines features associated with Di‐George anomaly and dup(9p). The chromo‐some abnormality in this patient appears to have arisen in a maternal germ cell due to adjacent type II disjunction.