bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome mosaicism in hypomelanosis of Ito
Authors: Ritter Catherine L. , Steele Mark W. , Wenger Sharon L. , Cohen Bernard A.
Published: June 2005

Our finding of chromosome mosaicism with a ring 22 in a retarded black boy with hypomelanosis of Ito prompted a review of this “syndrome.” Most patients have a variety of non‐dermal defects, particularly those affecting CNS function. Among karyotyped patients, most are chromosome mosaics of one sort or another. Hypomelanosis of Ito turns out to be a causable non‐specific phenotype, i.e., a clinical marker for chromosome mosaicism of all different types in individuals with a dark enough skin to show lighter patches. Consequently, cytogenetic evaluation is indicated in all patients with this skin finding.
Neuropsychological dysfunction among affected heterozygous fragile X females
Authors: Grigsby James P. , Kemper Melinda B. , Hagerman Randi J. , Myers Carol S.
Published: June 2005

Fragile X (or Martin‐Bell) syndrome is an X‐linked disorder that often produces mental retardation in males, but usually affects heterozygous females to a lesser degree. Here we report the results of a brief neuropsychological examination of 20 heterozygous fra(x) girls and women and two control groups of 20 individuals each. One control group was composed of fra(x)‐negative mothers (obligate carriers) and sisters of male probands with fra(x) syndrome, whereas the other was composed of 14 head‐injured and six learning disabled women and girls. In addition to general intellectual impairment, several specific cognitive deficits were consistently found in individuals with the Martin‐Bell syndrome, suggesting focal neuropsychological dysfunction.

Significant differences were noted between fra(x) individuals and controls on most cognitive and neuropsychological measures studied. Over one‐third of the fra(x) individuals demonstrated neuropsychological symptoms characteristic of the full developmental Gerstmann syndrome, whereas another third had three or four of the five signs of possible parietal lobe dysfunction. In our sample, there was an association between improved performance and increasing age. Differences among heterozygous individuals in number of focal symptoms may reflect some variability in the penetrance of the fra(x) gene, as well as in the functional organization of the brain.
The central nervous system in the Apert syndrome
Authors: Cohen M. Michael , Kreiborg Sven
Published: June 2005

In this paper, we present available central nervous system data from our series of patients with the Apert syndrome. Combining our own data with that available in the literature, 30 patients had malformations of the corpus callosum, the limbic structures, or both. Other frequent findings included megalencephaly (7 cases), gyral abnormalities (8 cases), encephalocele (4 cases), pyramidal tract abnormalities (2 cases), hypoplasia of cerebral white matter (4 cases), and heterotopic gray matter (2 cases). Progressive hydrocephalus seems to be uncommon and has frequently been confused with nonprogressive ventriculomegaly in the past. Psychometric evaluations, neurological findings, and neuropathologic reports from the literature are critically reviewed. It is clear that a significant number of patients with the Apert syndrome are mentally retarded. It is suggested that malformations of the central nervous system may be responsible for most cases.
Partial deletion of the long arm of chromosome 11 [del(11)(q23.3→qter)] with abnormal white matter
Authors: Wardinsky Terrance D. , Weinberger Ed , Pagon Roberta A. , Clarren Sterling K. , Thuline Horace C.
Published: June 2005

A patient with partial deletion of the long arm of chromosome 11[del(11)(q23.3→qter)] had macrocephalic trigonocephaly, growth and mental retardation, congenital heart defect, and characteristic facial appearance familiar to that of 33 other reported patients with this deletion. Computed tomography (CT) and magnetic resonance imaging of this infant's brain demonstrated abnormality of the supratentorial white matter. This may represent either deficiency or delay in myelination or possibly a demyelination process. No abnormalities in white matter were described in seven of 33 previously reported patients whose brains were examined by ultrasound, CT, or autopsy.
Chromosome 6q deletions: A report of two additional cases and a review of the literature
Authors: McLeod D. R. , Fowlow S. B. , Robertson A. , Samcoe D. , Burgess I. , Hoo J. J.
Published: June 2005

Here we report on two additional cases of distal 6q deletions with one case showing a terminal deletion of chromosome 6 (46,XY, del(6)(pter → q26:)) and one case showing an interstitial deletion of chromosome 6 (46,XY, del(6)(pter → q23::q25 → qter)). The association of retinal abnormalities in 6q deletions is supported, and the additional manifestations of skin hyperextensibility, sacral abnormality, and imperforate anus are described.
Neonatal progeroid syndrome: More than one disease?
Authors: Hagadorn James I. , Wilson William G. , Hogge W. Allen , Callicott Joseph H. , Beale Ernest F.
Published: June 2005

We report on an infant with the neonatal progeroid syndrome whose clinical course and autopsy findings indicate that this may be a heterogeneous phenotype. The infant had intrauterine growth retardation, absence of subcutaneous fat, and a wizened, aged face, all apparently characteristic of the condition, but also had congenital heart defects and urinary reflux not reported in previous cases. An elevated maternal serum alpha fetoprotein was noted at 16 weeks of gestation and lateonset growth retardation appeared after 31 weeks. Autopsy findings showed normal cerebral myelination, in contrast to findings of sudanophilic leukodystrophy in the one patient with the syndrome previously examined at autopsy. These findings suggest that the neonatal progeroid syndrome may be a phenotype and have more than one cause.
Facial morphometrics in the identification of gene carriers of X‐linked hypohidrotic ectodermal dysplasia
Authors: Saksena Sudha Srikrishen , Bixler David
Published: June 2005

Roentgenographic measurements and morphometric analysis were employed in the investigation of contrasting patterns of craniofacial variation between normal individuals and those affected by X‐linked hypohidrotic ectodermal dysplasia (HED). The research objective was to identify and describe the facial characteristics of heterozygous gene carriers who show minor expression of the disorder.

In this study of 13 HED families with 16 affected males, 12 carriers, and 12 normal individuals, affected individuals had at least 3 of the following 4 clinical signs and symptoms: a) hypodontia, b) hypohidrosis, c) hypotrichosis, and d) clinically distinct facial physiognomy. By contrast, the gene carriers manifested only one or 2 or none of the 4 clinical manifestations.

In a preliminary comparison of gene carriers vs. normal individuals, we have generated 2 discriminant functions (each based on 3 facial measurements taken either from the lateral or frontal cephalograms). These 2 functions correctly diagnose 100% of the gene carriers and normal HED relatives.

Facial anomalies characteristic of the gene carriers were 1) abnormally narrow and short maxillary width and palatal depth dimensions; 2) very small and retrusive malar and maxillary regions; 3) markedly reduced lower facial depth, height and width dimensions; 4) small head height, prominent forehead, and high‐set orbits; 5) a generalized, symmetric reduction of the whole craniofacial complex.
Clinical/Epidemiological analysis of malformations
Authors: Martinez‐Frías M. L. , Frías J. L. , Salvador J.
Published: June 2005

To investigate the heterogeneity of congenital malformations, we analyzed the distribution of 14 selected anomalies among 11,421 children with isolated defects and with different patterns of multiple congenital anomalies (MCA). Our study showed a marked variability in the distribution of each of these malformations. For example, although anophthalmia/microphthalmia, cleft palate, and limb deficiency were observed in all etiological categories of syndromes, no case with anencephaly was identified among the 1,244 children with different syndromes. Diaphragmatic hernia, esophageal atresia ± tracheoesophageal fistula, and gastroschisis were not found in any monogenic syndrome in this sample. These observations may be of help to the clinician in the evaluation of individual children with MCA.
A de novo X; 3 translocation in Rett syndrome
Authors: Zoghbi H. Y. , Ledbetter D. H. , Schultz R. , Percy A. K. , Glaze D. G.
Published: June 2005

Rett syndrome is a neurodegenerative disorder that occurs exclusively in females. The syndrome is sporadic in most cases with the exception of a few familial cases with an inheritance pattern through maternal lines. These observations raised the possibility that Rett syndrome may be due to an X‐linked dominant mutation which is lethal in the male. To evaluate this hypothesis, we have systematically performed high‐resolution chromosome analysis on 28 patients with Rett syndrome searching for deletions and/or translocations. In one patient, a de novo balanced translocation was observed with the chromosome constitution of 46, X, t (X;3) (p22.11;q13.31). This finding supports the hypothesis of an X‐linked dominant mutation and suggests that the Rett gene might map to distal Xp21 or proximal Xp22.
Transabdominal and transcervical chorionic villus sampling: Efficiency and risk evaluation of 2,411 cases
Authors: Brambati Bruno , Lanzani Alessandro , Tului Lucia
Published: June 2005

Efficacy and risks of transcervical and trans‐abdominal chorionic villus sampling (CVS) methods were evaluated in 1,501 and 910 cases, respectively. We reported a success rate of more than 99% for both sampling procedures and obtained an adequate amount of chorionic tissue in more than 96% of cases on the first attempt. However, the transcervical method was more difficult to learn and was contraindicated by a higher number of unfavorable clinical and anatomical conditions. Transabdominal sampling proved to be a less time‐consuming procedure and could also be used after the 12th week of gestation.

Bleeding/spotting (10.1%) and uterine cramping (2.5%) were the most frequent early complications following transcervical and transabdominal sampling, respectively. Uterine infection was rare (0.13%) and was reported only after cervical aspiration. No significant effects on fetal growth, preterm delivery, placenta disorders, congenital defects, and perinatal mortality following transcervical and transabdominal sampling, and for both procedures total fetal loss rate was less than 4%.

This experience suggests that transabdominal needle sampling is the method of choice; however, transcervical aspiration appears more likely to succeed in a limited number of well‐defined conditions.
Incidence and timing of pregnancy losses: Relevance to evaluating safety of early prenatal diagnosis
Authors: Simpson Joe Leigh
Published: June 2005

Knowing the frequency and timing of pregnancy loss during normal gestation is integral to evaluating the safety of prenatal diagnostic techniques. That preclinical loss rates are high in humans has long been suspected, but in the past decade new data concerning these losses have become available. Cohort studies indicate that many women who show positive β‐HCG assays never show clinical evidence of pregnancy. Cytogenetic abnormalities have also recently been documented in 20% of ostensibly normal in vitro fertilization embryos. All the above are consistent with the sentinal studies of Hertig and Rock, who showed high frequencies of morphological abnormalities in preimplantation embryos. The frequency of fetal losses after clinical recognition of pregnancy is 12–15%; however, more sensitive (ultrasonographic) methods of detecting fetal demise now indicate that most clinically recognized pregnancies occur prior to 8–9 weeks, being retained in utero 2–3 weeks prior to expulsion. Loss rates are influenced by maternal age, smoking, alcohol, and other confounding variables that if not taken into account could yield spurious results concerning safety of prenatal diagnostic techniques. After 8 weeks gestation the likelihood of losing a viable pregnancy is only 3% and after 16 weeks only 1%.
Current assessment of fetal losses as a direct consequence of chorionic villus sampling
Authors: Goldberg James D. , Porter Alison E. , Golbus Mitchell S.
Published: June 2005

Chorionic villus sampling has been developed as a method of first trimester prenatal diagnosis. In order to evaluate this new approach, accurate risk figures for the procedure must be obtained. This has been difficult for a number of reasons, including establishment of baseline fetal loss rates in the first trimester, procedural “learning curves,” and reporting biases. This review will discuss these problems and use data from the chorionic villus sampling program at the University of California, San Francisco, to illustrate difficulties in data interpretation.
Legal and ethical implications of fetal diagnosis and gene therapy
Authors: Annas George J. , Elias Sherman
Published: June 2005

With rapidly expanding capabilities in prenatal diagnosis and treatment resulting from new technologies, the medical profession is increasingly being confronted with legal uncertainties and ethical dilemmas. In this paper, we review current acceptable standards of care in the area of medical practice as related to genetic counseling and prenatal diagnosis. We emphasize that any attempts at therapeutic genetic intervention be carried out only 1) when there is reasonable scientific evidence that it will cure or prevent a disabling disease, and b) with the informed, voluntary, competent, and understanding consent of the individuals involved.
Carpenter syndrome: Marked variability of expression to include the summitt and Goodman syndromes
Authors: Gershoni‐Baruch Ruth
Published: June 2005

Here we report on two sibs with Carpenter syndrome showing marked intrafamilial variability. One patient had craniosynostosis of the sagittal suture, normal intelligence, and no abnormalities of hands and feet. The second patient had polysyndactyly of hands and feet, normal intelligence, and no craniosynostosis. The diagnosis of Carpenter syndrome was made after the second affected child in the family was born. This report emphasizes previous suggestions that acrocephalopolysyndactyly, type II, has variable clinical expression. It is suggested that polysyndactyly of feet is not an absolute requisite for the diagnosis of Carpenter syndrome. This allows the inclusion of Summitt and Goodman syndromes within the clinical spectrum of this disorder.
Aspartoacylase deficiency and Canavan disease in Saudi Arabia
Authors: Ozand Pinar T. , Gascon Generoso G. , Dhalla Mohammed
Published: June 2005

We found defective aspartoacylase activity in fibroblasts cultured from 12 patients with leukodystrophy clinically diagnosed as spongy degeneration of the brain (Canavan disease), three confirmed by brain biopsy. The activity of aspartoacylase ranged between 1 and 13% of two groups of control individuals, normals, and those with other leukodystrophies. The present report confirms the study of Matalon et al. [1988] in a totally different ethnic group and provides independent verification that aspartoacylase activity is the first documented specific biochemical marker in Canavan disease and plays an important role in pathogenesis. Considering that only some 75 cases had been reported up to 1982, our group of 12, accumulated within 3 years, is inordinately large and suggests that Saudi Arabia provides a promising venue in which to study the biochemical and molecular genetics of Canavan disease.
Loss of the 3p25.3 band is critical in the manifestation of del(3p) syndrome: Karyotype‐phenotype correlation in cases with deficiency of the distal portion of the short arm of chromosome 3
Authors: Narahara Kouji , Kikkawa Kiyoshi , Murakami Masae , Hiramoto Kei , Namba Hiroshi , Tsuji Kazushiro , Yokoyama Yuji , Kimoto Hiroshi
Published: June 2005

Two patients with monosomy for the distal portion of the short arm of chromosome 3 are described. Chromosome analysis on prometaphase cells demonstrated a karyotype of 46,XX, del(3) (p25.3) in one patient and 46,XX, r(3)(p26.1q29) in the other. The former patient showed characteristic clinical manifestations of the 3p‐ syndrome, including growth failure, mental retardation, microcephaly with a flat occiput, triangular face, synophrys, blepharoptosis, hypertelorism, broad and flat nose, long philtrum, downturned mouth, micrognathia, apparently lowset and malformed ears, finger abnormalities, and deafness. The latter patient had a nonspecific phenotype with mental retardation, growth failure and microcephaly. Karyotypephenotype comparisons in the present cases and 16 previously reported cases with deficiency of the distal portion of 3p suggests that deficiency of the 3p25.3 band is critical to produce the main clinical manifestations of the del(3p) syndrome.
Autosomal recessive hydrocephalus with third ventricle obstruction
Authors: Chow C. W. , McKelvie P. A. , Anderson R. McD. , Phelan E. M. D. , Klug G. L. , Rogers J. G.
Published: June 2005

Here we report a brother and sister who presented in the neonatal period with hydrocephalus. Ultrasonography showed marked dilatation of the lateral ventricles but not the third ventricle. One child with postnatal onset was shunted and had normal development at 3 years. The other child had severe hydrocephalus at birth and was not treated. Neuropathologic studies demonstrated dilatation of the lateral ventricles and marked narrowing of the posterior part of the third ventricle but no other malformations other than those that result directly from hydrocephalus. The potential for a good prognosis is emphasized.
Oral–facial–digital syndrome type VI (Váradi syndrome): Further clinical delineation
Authors: Münke Maximilian , McDonald Donna M. , Cronister Amy , Stewart Janet M. , Gorlin Robert J. , Zackai Elaine H.
Published: June 2005

Cerebellar anomalies are consistent findings in patients with the oral–facial–digital syndrome type VI (Váradi syndrome) in addition to variable facial and oral changes, and polysyndactyly of hands and feet. We report 3 unrelated patients with this entity who have a hypoplastic cerebellar vermis shown by magnetic resonance imaging (MRI), as well as clinical signs of cerebellar defect. Polydactyly of the hands is characterized by a central Y‐shaped metacarpal. Clinically recurrent episodes of tachypnea and hyperpnea are remarkable. Postnatal growth is delayed with short stature in all 3 patients possibly due to growth hormone deficiency in one of them. In contrast to reported patients who are all severely mentally retarded, one of our patients is of normal intelligence. Type VI oral‐facial‐digital syndrome is an autosomal‐recessive trait and may be detected prenatally.
Previously unrecognized congenital progeroid disorder
Authors: Petty Elizabeth M. , Laxova Renata , Wiedemann Hans‐Rudolf
Published: June 2005

We report on a 5‐year‐old girl with a progeroid disorder and compare her to a previously reported woman now in her forties, whom she resembles to a striking degree. Common manifestations include pre‐ and post‐natal growth retardation, markedly diminished subcutaneous fat, wrinkled skin, abnormally scant hair growth, hypoplastic distal phalanges with hypoplastic nails, umbilical hernia, large open anterior fontanelle, and normal cognitive and motor development. Both patients have had a prematurely aged appearance since birth. These 2 patients appear so different from previously reported patients with progeroid disorders that they may represent a separate entity.
Pathogenesis of the lethal multiple pterygium syndrome
Authors: Moerman Philippe , Fryns Jean‐Pierre , Cornelis Ann , Bergmans Guido , Vandenberghe Kamiel , Lauweryns Joseph M.
Published: June 2005

We present autopsy studies in 4 unrelated fetuses with the lethal multiple pterygium syndrome (LMPS) with special emphasis on the neuromuscular system. The data suggest that LMPS combines the manifestations of a jugular lymphatic obstruction sequence with those of an early severe fetal akinesia sequence. The jugular lymphatic obstruction sequence with resultant edema and cystic hygroma colli causes fetal lethality usually in the second trimester of pregnancy. Generalized amyoplasia appears to be an important mechanism in the pathogenesis of fetal akinesia as part of LMPS and is not associated with dysgenesis or degeneration of the central nervous system (CNS) but is apparently the result of an early fetal muscular “dystrophy.” We propose a genetically determined insult affecting the early embryonic development of both lymph vessels and muscles as the basic defect in LMPS. Placental structure, studied in all 4 cases, demonstrated that triploidy‐like placental lesions are specific to LMPS. The present findings suggest that LMPS may be a less heterogeneous entity than previously proposed.
Hypomelanosis of Ito—a nonspecific marker of somatic mosaicism: Report of case with trisomy 18 mosaicism
Authors: Chitayat David , Friedman J. M. , Johnston Margaret M.
Published: June 2005

We report on a patient with hypomelanosis of Ito (HI), developmental delay, recurrent pneumonia, and facial asymmetry. Chromosome analysis done on blood and on one of three skin biopsies showed trisomy 18 mosaicism. This is the first report of HI associated with trisomy 18 mosaicism. This neuroectodermal disorder appears to be a nonspecific manifestation of chromosome mosaicism.
Stepwise oligogenic segregation and linkage analysis illustrated with dopamine‐β‐hydroxylase activity
Authors: Wilson A. F. , Elston R. C. , Sellers T. A. , Bailey‐Wilson J. E. , Gersting J. M. , Deen D. K. , Sorant A. J. M. , Tran L. D. , Amos C. I. , Siervogel R. M.
Published: June 2005

A stepwise oligogenic method is developed that can be used to adjust the phenotype of a quantitative trait for the effects of a previously identified single‐locus component. This method assumes that a single‐locus component can be adequately identified through the use of segregation and/or linkage analysis under a 1‐locus model and that the variation due to that locus can be removed from the phenotype leaving a residual that can be parameterized in terms of an additional single‐locus component. Segregation and/or linkage analysis can then be used in an attempt to identify an additional single‐locus component in the residual phenotype. This stepwise process can be repeated until no further single‐locus effects are identified. The method is illustrated using family data on the specific activity of dopamine‐β‐hydroxylase (DBH), which a number of studies have suggested may be due either to the combined effects of singlelocus and multifactorial components or to the combined effects of 2 loci.
Neuroblastoma in a child with Wiedemann–Beckwith syndrome
Authors: Chitayat David , Friedman J. M. , Dimmick James E.
Published: June 2005

We report on a patient with Wiedemann‐Beckwith syndrome (WBS) who developed abdominal neuroblastoma. Although WBS patients are known to have a higher incidence of embryonal tumors, this is only the 4th known case of neuroblastoma associated with this syndrome. Chromosomes on peripheral lymphocytes and tumor cells were normal. Children with WBS should be screened for a variety of embryonal neoplasms, not only Wilms tumor.
Hereditary cranium bifidum and symmetric parietal foramina are the same entity
Authors: Little Bertis B. , Knoll Kraig A. , Klein Victor R. , Heller Karen B.
Published: June 2005

Cranium bifidum is literally “cleft skull.” Numerous reports describe the anatomy of this defect, and crude estimates of the population prevalence suggest it is a relatively infrequent occurrence. McKusick's catalog contains only one family with cranium bifidum but several familial reports of symmetrical parietal foramina. Available information indicates that cranium bifidum and symmetrical parietal foramina are inherited in an autosomal dominant fashion and occur in orientals, blacks, whites, and native Americans. Here we report on a family with serial radiographs that document ontogenic development of parietal foramina in late childhood and adulthood from apparent cranium bifidum and parietal foramina during infancy and early childhood. We conclude that these are the same entity, differentiated only by the time during life in which the defect is demonstrated.
Syndrome of partial aniridia, cerebellar ataxia, and mental retardation—Gillespie syndrome
Authors: Nevin N. C. , Lim J. H. K.
Published: June 2005

Here we describe a 5‐year‐old girl with Gillespie syndrome of cerebellar ataxia, partial aniridia, and mental retardation. The Gillespie syndrome probably is an autosomal recessive trait.
Johanson‐Blizzard syndrome: Clinical spectrum and further delineation of the syndrome
Authors: Gershoni‐Baruch Ruth , Lerner Aaron , Braun Jacob , Katzir Yossef , Iancu Theodore C. , Benderly Avraham
Published: June 2005

We report on 2 patients with Johanson blizzard syndrome and review the literature, in an attempt to further characterize the clinical spectrum of this disorder.
Dubowitz syndrome: Possible evidence for a clinical subtype
Authors: Ilyina Helena G. , Lurie Iosif W.
Published: June 2005

Clinico‐genetic analysis of 21 personal observations and review of the literature confirmed the existence of a wide phenotypic spectrum of Dubowitz syndrome. It is shown that in spite of marked microcephaly, severe mental deficiency is rare in Dubowitz syndrome and about half of the patients are mentally normal. A “new” clinical subtype is defined, which also includes anorectal anomalies and premature craniosynostosis. All three families with this form are natives of a small area of Byelorussia, suggesting an autosomal or X‐linked recessive mode of inheritance of this subtype. The data obtained confirm autosomal recessive inheritance of Dubowitz syndrome.
Trisomy 22 in a liveborn infant with multiple congenital anomalies
Authors: McPherson Elspeth , Stetka Daniel G.
Published: June 2005

We report on the third confirmed case of trisomy 22 in a liveborn infant. High‐resolution banding studies ruled out translocations such as the relatively common t(11;22). The infant shared many manifestations with other reported cases of trisomy 22 (e.g., growth deficiency, microcephaly, micrognathia, ear malformations, cleft palate, and congenital heart defect) and some manifestations in common with dup 22. Trisomy 22 appears to cause a severe malformation syndrome, and survival to term is rare.
Infantile hypophosphatasia: Autosomal recessive transmission to two related sibships
Authors: Moore Cynthia A. , Ward Jewell C. , Rivas Marian L. , Magill H. Lynn , Whyte Michael P.
Published: June 2005

Hypophosphatasia, a rare heritable form of rickets/osteomalacia, is characterized by deficient activity of the tissue nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequence of either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213–234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality.

We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5 1/2 years and has had a much milder clinical course. Although consanguinity is absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are consistent with heterozygosity in each parent. Fibroblast ALP activity is <1% normal in all 3 patients with no complementation observed in heterokaryon analysis. Accordingly, the genetic defects appear to be identical in all 3 patients. Our findings show that infantile hypophosphatasia may be inherited as an AR condition where there is variable expressivity and that homozygosity or compound heterozygosity, as may be the case in this family, is not necessarily lethal.
A prevalence study of rett syndrome in an institutionalized population
Authors: Burd Larry , Martsolf John T. , Randall Tim
Published: June 2005

An institution for the mentally retarded was surveyed to determine the prevalence rate of Rett syndrome (RS). Four patients with definite RS and one with probable RS were identified in a population of 350, yielding a prevalence rate of 1 in 87, about 1% of institutionalized male and female patients with mental retardation. In this population of patients with severe and profound mental retardation (N = 297), 138 females were surveyed, suggesting a prevalence rate among females of 1 in 34 in an institutional population of persons with mental retardation. Surveys of institutions for persons with mental retardation may be an effective method to identify adults with RS.
Obesity, hypertension, and renal disease in relatives of Bardet‐Biedl syndrome sibs
Authors: Croft Janet B. , Swift Michael
Published: June 2005

The Bardet‐Biedl syndrome is a rare autosomal recessive disorder characterized by pigmentary retinopathy, obesity, polydactyly, hypogonadism, and mental retardation. Renal abnormalities, hypertension, acquired heart disease, and hepatic fibrosis also occur in homozygotes. Two adult Bardet‐Biedl sibs, a man with hypertension and cardiomegaly and a woman with biliary cirrhosis, and 75 relatives in 5 generations of the extended family were identified. Hospital records for major illnesses, death certificates, and autopsy reports were examined. The frequent observation of obesity, hypertension, diabetes mellitus, and renal disease in first‐degree relatives, obligate gene carriers, and other blood relatives raise the possibility that Bardet‐Biedl heterozygotes are also predisposed to these disorders.
DNA linkage analysis and studies of the androgen receptor gene in a large kindred with complete androgen insensitivity
Authors: Imperato‐McGinley Julianne , Ip Nancy Y. , Gautier Teofilo , Neuweiler John , Gruenspan Harry , Liao Shutsung , Chang Chawnshang , Balazs Ivan
Published: June 2005

DNA linkage analysis of the X chromosome and studies with cDNA probes specific for the androgen receptor gene were performed on the largest known kindred with the syndrome of complete androgen insensitivity. The affected subjects (XY) have absent binding of dihydrotestosterone to the androgen receptor (the receptor negative form of androgen insensitivity). In this kindred there was maternal transmission of the gene, with all affected males expressing complete genital feminization. Linkage analysis studies were conducted with two DNA probes, DXS1 and PGK1, localized to the Xq11–Xq13 region of the long arm of the X chromosome near the centromere. The results demonstrate linkage to the markers in the order of DXS1‐(AR; PGK1), thus localizing the AR gene to an area between Xq11 and Xq13. Three cDNA probes that span various parts of the androgen receptor gene, including the DNA and steroid binding domain, were used to evaluate the androgen receptor gene in normal individuals, carrier mothers, and affected subjects. Identical restriction fragment patterns were found in all three groups studied. Thus the androgen receptor gene was present in affected subjects without detectable DNA polymorphism at the androgen binding domain. Therefore, despite complete absence of binding to the androgen receptor, the defect in the androgen receptor gene in this kindred is not the result of a gene deletion. The results point to a mutation or a small insertion/deletion as the probable cause of the syndrome.
Two brothers with mental retardation discordant for the Fragile‐X syndrome
Authors: van Roy Bernadette C. , Willems Patrick J. , Vits Lieve J. , Ceulemans Berten P. , Coucke Paul J. , van der Auwera Bart J. , Lormans Jacques A. G. , Dumon Jan E.
Published: June 2005

We describe two male sibs with mental retardation discordant for the fragile‐X syndrome. In the younger sib, chromosome analysis under folate deprivation showed a fragile site at Xq27.3 in 12‐46% of mitoses. In the older sib, however, repeated chromosome analyses (six different cultures with analysis of 50 mitoses each) under identical conditions could not detect any fragile‐X site. Using DNA probes linked to the fragile‐X gene, we found evidence that the two sibs inherited a different maternal X chromosome at Xq27.3. This excluded the presence of the fragile‐X syndrome in the older sib with a probability of greater than 99%.
Syndrome of a craniofacial dysostosis, limb malformation, and omphalocele
Authors: Gardner R. J. M. , Morrison P. S. , Faigan L. A. , Kennedy J. C. , Fitzgerald P. H.
Published: June 2005

We describe an infant with a unique combination of a severe craniofacial dysostosis and a very distinctive facies, severe limb defects, a thoracic deformity, and an omphalocele as the major anomalies. We propose that this represents a “new” syndrome of multiple congenital abnormalities.
Cor pulmonale as a complication of methylmalonic acidemia and homocystinuria (Cb1‐C type)
Authors: Brandstetter Yuval , Weinhouse Elliott , Splaingard Mark L. , Tang Thomas T.
Published: June 2005

We report an infant with a bronchiolitis‐like illness and rapid deterioration who developed a cor pulmonale‐like picture with a dilated right ventricle. Urinary organic acid assays established a probable diagnosis of Cbl‐C‐type methylmalonic aciduria, later confirmed by complementation studies. Despite medical intervention and cyanocobalamin treatment the patient died on his tenth hospital day. Postmortem examination showed the presence of thromboemboli in the pulmonary circulation. We hypothesize that acute cor pulmonale developed in this infant secondary to thromboembolism of his pulmonary circulation. A review of the literature shows that thromboembolism may be a part of this disease process.
Case of direct insertion within a chromosome 3 leading to a chromosome 3p duplication in an offspring
Authors: Watson Michael S. , Dowton S. Bruce , Rohrbaugh James
Published: June 2005

An infant with developmental delay and multiple minor congenital anomalies had a duplication of bands p11.1→p14.2 in 3p. Maternal chromosome studies demonstrated a direct intrachromosomal insertion within chromosome 3p.
The popliteal pterygium syndrome: Report of a new family and review of the literature
Authors: Hunter Alasdair
Published: June 2005

This paper reports on a family with popliteal pterygium syndrome (PPS), which was ascertained through a baby with most of the major signs of the syndrome. The mother, who had a repaired cleft palate and toe syndactyly, had been aware that her syndactyly was familial, but her unpreparedness for the birth of a child with PPS led to interest in, and a subsequent review of, the differential diagnosis and the variable expression of the clinical manifestations of this syndrome. Upon review, some earlier reported cases were excluded as PPS, and certain ascertainment and reporting biases that could affect such an analysis were considered.
Heterogeneity in the familial aggregation of fasting serum uric acid level in five North American populations: The lipid research clinics family study
Authors: Rice Treva , Vogler George P. , Perry Tammy S. , Laskarzewski Peter M. , Province Michael A. , Rao D. C.
Published: June 2005

This study represents the first formal examination for heterogeneity in the familial aggregation of fasting serum uric acid (UA) levels. Data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) participating in the Lipid Research Clinics (LRC) family study, which included a total of 685 nuclear families (N = 2, 146), were analyzed. Heterogeneity among the clinics in familial resemblance was detected. However, this heterogeneity could not be attributed to differences in distributional properties (such as means and variances) or to path model parameters representing latent genetic or cultural (environmental) components associated with UA levels. Intergenerational differences in genetic heritabilities were found, with higher offspring (h2 = 43%) than parent (h2z2 = 16%) estimates, but no generational differences were detected for cultural heritability (c2 = 0.09). Equal maternal and paternal cultural transmission was found, and effects due to extra sibling environments and to marital resemblance were both significant. These results show no clear indication as to the source of the heterogeneity observed for familial resemblance of UA levels in randomly selected data. This question should be further investigated, especially in clinical samples such as dyslipoproteinemic families.
Oto‐palato‐digital syndrome, type II: Evidence for defective intramembranous ossification
Authors: Ogata Tsutomu , Matsuo Nobutake , Nishimura Gen , Hajikano Hiroshi
Published: June 2005

We report on a Japanese boy with cto‐palato‐digital syndrome type II, an X‐linked lethal congenital skeletal dysplasia. The clinical, radiological, and histological findings indicate that defective intramembranous ossification may be the principal abnormality responsible for the entity.
Syndrome of brittle cornea, blue sclera, and joint hyperextensibility
Authors: Zlotogora Joel , BenEzra David , Cohen Tirza , Cohen Evelyne
Published: June 2005

In 3 families 4 patients were affected with the syndrome of brittle cornea, blue sclera, and hyperextensible joints (brittle cornea syndrome). From the review of 17 affected patients described previously and our cases, it appears that this rare autosomal recessive syndrome has variable expressivity. Two different groups of patients may be distinguished: one includes 5 families, all of Tunisian Jewish origin. All patients in this group also have red hair. In the second group, 9 families are from various ethnic origins; affected patients in this group have a normal distribution of hair color. A possible explanation for the existence of these 2 different group of patients is that the locus of the gene responsible for the syndrome is closely linked to the locus for a gene responsible for hair color with linkage disiquilibrium in Tunisian Jews (Sepharadim).
Hypodipsic hypernatremia and hypertriglyceridemia associated with cleft lip and cleft palate: A new hypothalamic dysfunction syndrome?
Authors: Ben‐Amitai Dan , Rachmel Avinoam , Levy Yael , Sivan Yakov , Nitzan Menachem , Steinherz Reuben
Published: June 2005

We report on a 4‐month‐old girl with congenital hypodipsic hypernatremia resulting from decreased sensitivity of the hypothalamic osmoreceptors with increased tonicity in association with hyperlipemia and cleft lip and cleft palate. We postulate that the link among these various derangements is hypothalamic Dysfunction.
Possible heterogeneity in spondyloenchondrodysplasia: Quadriparesis, basal ganglia calcifications, and chondrocyte inclusions
Authors: Frydman Moshe , Bar‐Ziv Jacob , Preminger‐Shapiro Rivka , Brezner Amichai , Brand Natan , Ben‐Ami Tamar , Lachman Ralph S. , Gruber Helen E. , Rimoin David L.
Published: June 2005

We report on 6 patients with short stature and progressive enchondromatous‐like changes of the vertebral bodies and the metaphyses of the long bones. Parental consanguinity was observed in 5 of 6 cases, supporting autosomal recessive inheritance. In spite of the similarity in radiographic changes and body proportions, genetic heterogeneity is suggested by the presence of CNS calcifications in 3 patients. Two of the latter had progressive quadriparesis. We tentatively classified these patients into 2 provisional types.

An iliac crest biopsy in one of the patients with “type I” disease did not demonstrate enchondromatosis. Light and transmission electron microscopic studies demonstrated large cisterns and small inclusion bodies containing a flocculent material within the rough endoplasmic reticulum of the chondrocytes. Based on the histological and radiographic findings, we propose to classify these conditions among the spondylometaphyseal skeletal dysplasias.
Holoprosencephaly in an infant with a minute deletion of chromosome 21(q22.3)
Authors: Estabrooks Laurel L. , Rao Kathleen W. , Donahue Roger P. , Aylsworth Arthur S.
Published: June 2005

We evaluated an infant because holoprosencephaly had been detected by prenatal ultrasound examination and magnetic resonance imaging (MRI). Postnatally, high‐resolution cytogenetic studies showed a minute deletion of chromosome 21(q22.3). This patient lacks many of the characteristics associated with monosomy 21, partial monosomy 21, and ring 21 chromosome patients. She also lacks the midline facial abnormalities often seen with holoprosencephaly. The similarity in facial appearance between this case and one previously reported patient with holoprosencephaly and a ring chromosome 21 suggests a causal relationship between holoprosencephaly and deletion of chromosome 21(q22.3). These findings also suggest that infants and children with developmental delay and apparently normal facial appearance should be examined for holoprosencephaly and that all identified patients with holoprosencephaly need high‐resolution cytogenetic studies with careful attention to the terminal portion of 21q.
Familial congenital diaphragmatic defect and associated midline anomalies: Further evidence for an X‐linked midline gene?
Authors: Carmi R. , Meizner I. , Katz M.
Published: June 2005

We report on familial occurrence of congenital diaphragmatic defect and associated midline anomalies, namely cleft palate and omphalocele in brothers. This family further supports the existence of an X‐linked gene involved in the organization of the embryonal midline. This particular mutant gene might be active in the schisis‐morphogenesis phenomena occurring at the midline.
De novo direct Tandem duplication of the short arm of chromosome 7(p21.1‐p14.2)
Authors: Dȩbiec‐Rychter Maria , Overhauser Joan , Kałuźewski Bogdan , Jakubowski Lucjusz , Truszczak Barbara , Wilson Wesley , Skorski Maria , Jackson Laird
Published: June 2005

We report on a 6‐year‐old boy with moderate developmental retardation and unusual dermatoglyphics. Cytogenetic analysis demonstrated a duplication of chromosome subregion 7p21.2‐p14.2. Confirmation of the specific duplicated region was determined by quantitative Southern blotting by using a DNA fragment previously localized to the portion of chromosome 7 thought to be duplicated. This patient did not have the internal malformations seen with other dup(7p) patients.
Distal 12p deletion in a stillborn infant
Authors: Baroncini A. , Avellini C. , Neri C. , Forabosco A.
Published: June 2005

A stillborn female with a “de novo” deletion of band 12p13 is described. Her main clinical manifestations are intrauterine growth retardation, unilateral cleft lip, protruding tongue, and small, low set, and posteriorly angulated ears. Comparison of this case with 4 previous reported patients with an isolated distal del(12p) fails to show significant common phenotypic characteristics.
Familial sex chromosomal mosaicism
Authors: Juberg Richard C. , Holliday Daniel J. , Hennessy Victoria S.
Published: June 2005

Familial mosaicism has rarely been reported either for autosomes or sex chromosomes. Its recognition poses problems in prognosis, especially in prenatal diagnosis. Three generations of females showed sex chromosomal mosaicism with 3–4 cell lines, the diploid predominant. Phenotypic effect, if any, appeared limited to reduced fertility. The proposita, ascertained prenatally, has grown and developed normally. A dominant gene mechanism most likely accounts for the observations, either autosomal or X‐linked. If the mechanism in this family is monogenic, then the gene may not be strictly private considering the frequency of mosaic amniotic fluid cell cultures.
Midline facial defects with ocular colobomata
Authors: Temple I. K. , Brunner H. , Jones B. , Burn J. , Baraitser M.
Published: June 2005

We describe 5 children with midline facial anomalies and iris colobomata reminiscent of frontonasal “dysplasia.” Two patients have, in addition, abnormalities of the eyelids and one of them probably has the rare autosomal recessive condition frontofacionasal “dysplasia.” The patients may have a new syndrome of midline facial defects, iris colobomata, and mental retardation.
Craniosynostosis and lid anomalies: Report of a girl with Michels syndrome
Authors: Cunniff Christopher , Jones Kenneth Lyons
Published: June 2005

We report on a 2‐year‐old girl with Michels syndrome, a condition characterized by mental deficiency, craniosynostosis, blepharophimosis, ptosis, and epicanthus inversus. The phenotypic findings are compared with those of previously reported cases.
Microphthalmos in the presumed homozygous offspring of a first cousin marriage and linkage analysis of a locus in a family with autosomal dominant cerulean congenital cataracts
Authors: Bodker Fred S. , Lavery Mary Ann , Mitchell Thomas N. , Lovrien Everett W. , Maumenee Irene H.
Published: June 2005

A family with autosomal dominant congenital cataracts was studied to determine clinical variability. A total of 159 relatives was ascertained; 17 affected and 19 normal individuals were evaluated and their blood sampled for inclusion in the linkage analysis. The disease was compatible with normal to mildly decreased visual acuity until adult life in all affected except the product of a consanguineous marriage of affected first cousins who was born with bilateral microphthalmos and dense congenital cataracts, attributed to homozygosity of the cataract gene. There were no extraocular abnormalities; the patient was of normal intelligence. Twenty‐three markers were typed, 18 of which were informative. Linkage could be excluded for all 18 markers at short distances.
Parental origin of chromosome 5 deletions in the cri‐du‐chat syndrome
Authors: Overhauser J. , McMahon J. , Oberlender S. , Carlin M. E. , Niebuhr E. , Wasmuth J. J. , Lee‐Chen J.
Published: June 2005

The parental origin of de novo deletions leading to the cri‐du‐chat syndrome has been investigated. Since the cri‐du‐chat syndrome is correlated with deletions involving the short arm of chromosome 5 (5p), DNA fragments known to detect restriction fragment length polymorphisms (RFLPs) along 5p were used to establish whether the paternal or the maternal chromosome had suffered the deletion. In cases where only one parent was available, somatic cell hybrids were used in conjunction with RFLP analysis to determine the origin of the deleted chromosome. The deleted chromosome 5 was of paternal origin in 20/25 cases.
Walker‐warburg syndrome with microtia and absent auditory canals
Authors: Gershoni‐Baruch Ruth , Mandel Hanna , Miller Benjamin , Sujov Polo , Braun Jacob
Published: June 2005

Walker‐Warburg syndrome is a lethal, autosomal recessive disorder characterized by anomalies of the central nervous system and eye. Typical finding include hydrocephalus, agyria, retinal dysplasia, cerebellar dysgenesis, anterior chamber dysgenesis, and encephalocele. Recently, the phenotypic spectrum has been expanded to include congenital muscular dystrophy. Two sibs with Walker‐Warburg syndrome are reported. One sib had congenital glaucoma and hydrocephalus. The other sib had hydrocephalus, microtia, absent auditory canals, and pale retinas, barely within the phenotypic spectrum of the disorder. Elevation of muscle enzymes was consistent with the diagnosis of Walker‐Warburg syndrome.