bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability of expression of the orofaciodigital syndrome type I in black females: Six cases
Authors: Salinas Carlos F. , Pai G. Shashidhar , Vera Christian L. , Milutinovic Jovan , Hagerty Richard , Cooper Joel D. , Cagna David R.
Published: June 2005

Orofaciodigital syndrome type I (OFD I) includes striking orodental, facial, digital, renal, and central nervous system (CNS) abnormalities. Frequently associated with mental retardation, OFD I is inherited as an X‐linked dominant trait, lethal in males. Here, we report the variable expressivity of OFD I in 6 black U.S. females and review findings in 2 previously reported black patients. Only these 8 of over 160 reported cases involve blacks. Abnormalities observed in black patients are similar to those observed in whites, but with specific differences. Only 25% of the blacks had cleft palate and none was observed with midline cleft of the upper lip. Among whites, 80% have cleft palate and 45% midline cleft of the upper lip. These findings suggest that racial genetic factors may protect lip and palate development in blacks, even in the presence of the OFD I gene. CNS abnormalities, including agenesis of the corpus callosum, hydrocephaly, cystic brain lesions, seizures, and mental retardation, were present in 50% of our the cases. This figure is greater than previously reported. Polycystic kidneys were present in 3 of our patients. Including a previously reported patient, 50% of the black OFD I patients show polycystic kidneys. Hyperplastic and supernumerary frenula, with or without bra‐chydactyly, have been shown to be strong diagnostic criteria in our patients. New findings reported here include intracranial berry aneurysm, periodontal disease, and lip pits. Clinicians treating these patients should be aware of the pleiotropic manifestations of the syndrome, which may include renal and CNS anomalies. Ultrasonic and computed tomography scan studies are indicated in patients diagnosed with OFD I.
Screening of male patients with autosomal recessive Duchenne dystrophy through dystrophin and DNA studies
Authors: Vainzof Mariz , Pavanello Rita C. M. , Pavanello‐Filho Ivo , Rapaport Debora , Passos‐Bueno Maria Rita , Zubrzycka‐Gaarn Elizabeth E. , Bulman Dennis E. , Zatz Mayana
Published: June 2005

Previously we estimated that about 2.5–4% of isolated male patients diagnosed as Duchenne dystrophy (DMD) may have the autosomal recessive form (AR‐DMD). Such cases can be distinguished from X‐linked DMD through the analysis of dystrophin. Fifty DMD patients from 47 families were investigated for dystrophin and DNA deletions. Based on our results, we estimate that the frequency of AR‐DMD may be about 8–12% among male patients diagnosed as DMD in whom X‐linked inheritance could not be confirmed through pedigree data, serum enzymes in female relatives or DNA studies. Such an estimate must be confirmed in a larger sample; however, it shows the importance of assessing dystrophin in all patients diagnosed as DMD in whom X‐linked inheritance cannot be proved, since the distinction between these 2 forms has implications for genetic counseling.
CHARGE association: Clinical manifestations and developmental outcome
Authors: Harvey A. Simon , Leaper Patricia M. , Bankier Agnes
Published: June 2005

Mental retardation and growth failure are considered integral manifestations in the CHARGE association, reported to be present in as many as 90% of cases. Recent studies have reported a better than expected outcome in some patients; however, the conclusions of these studies have been confounded to some extent by their inclusion criteria. We report follow‐up of 17 patients with CHARGE association in whom the diagnosis was based on clinical findings present in early infancy, before developmental patterns were established. Of the 7 survivors, all had motor delay, and 6 had feeding difficulties during infancy. Psychometric assessment at follow‐up (age range 2 years, 10 months, to 15 years) showed that 2 were functioning in the normal range, 3 had specific language delay, one had moderate mental retardation, and one had severe mental retardation. Feeding problems persisted in only the 2 youngest patients. After initial failure to thrive, normal height was reached in 4 of 5 children older than age 3 years. The effects of visual and hearing deficits, their management, and the effects of physical illness are discussed with respect to developmental outcome. Our results suggest that some infants with CHARGE association who survive early infancy have a better prognosis for feeding difficulties, growth, and mental development than may be expected from early performance and better than that generally predicted from the current literature. The prompt management of sensory deficits is emphasized.
Macrostomia, ectropion, atrophic skin, hypertrichosis: Another observation
Authors: David Albert , Gordeeff André , Badoual Jean , Delaire Jean
Published: June 2005

We report on a boy with bilateral ectropion, ocular hypertelorism, bulbous nose, macrostomia with thin lips, abnormal ears, hypertrichosis of the forehead, neck and back, atrophic skin with hypoplastic nipples. Cause and inheritance are unknown.
Aging gametes in relation to incidence, gender, and twinning in Down syndrome
Authors: Sharav Teresa
Published: June 2005

Sexual practices have been implicated in the causation of Down syndrome (DS). Two mechanisms have been hypothesized. The theory of the fertilisation of an overripe ovum due to a delay in fertilization, and more recently the aging of the sperm. The orthodox Jewish population have very specific, strict practices concerning menstruation, which provide a unique model for the study of births in relation to time of conception. Data on the incidence of DS in the Jewish population of Jerusalem between 1982 and 1988 were analyzed. Among a comparable group of mothers under age 37 years and for whom amniocentesis was not available, it was found that the incidence of DS was significantly higher in the religious than in the nonreligious population (P < 0.001). The rate of twinning in the DS population was significantly higher than in the general population (P < 0.015), as was the ratio of males to females, 62% and 38%, respectively compared with 51% males and 49% females in the newborn population (P < 0.001). The association of these 3 factors in relation to the aging gamete of either maternal or paternal origin is discussed.
Prenatal diagnosis of hereditary amyloidosis in a Portuguese family
Authors: Morris Michael , Nichols William , Benson Merrill
Published: June 2005

Portuguese‐type amyloidosis is an autosomal dominant condition caused by a point mutation of the prealbumin (transthyretin) gene. The mutation can be detected directly by the presence of a restriction site for Nsil. We report the first prenatal diagnosis for this condition, performed in the first trimester by chorionic villus sampling, polymerase chain reaction, and restriction enzyme digestion.
Photogrammetric evaluation in clinical genetics: Theoretical considerations and experimental results
Authors: Diliberti John H. , Olson David P.
Published: June 2005

As newer mathematical approaches are applied to the field of clinical genetics accurate methods of craniofacial measurement are increasingly necessary. If photogrammetric techniques are to be used certain theoretical and practical issues must be taken into account. Errors due to projection are particularly important, but systematic and random errors must also be considered. We discuss theoretical aspects of projection errors along with experimental measurements. Systematic errors in excess of 20% were found during simulations of typical clinical conditions, although smaller errors were obtained using techniques practical in a clinical setting. Photogrammetric measurements are potentially valuable in the field of clinical genetics but must be used cautiously.
Renal dysgenesis in a monozygotic twin: Association with in utero exposure to indomethacin
Authors: Restaino Irene , Kaplan Bernard S. , Kaplan Paige , Rosenberg Henrietta Kotlus , Witzleben Camillus , Roberts Nancy
Published: June 2005

We report oligohydramnios and renal dysgenesis in one of identical twins, which might have resulted from in utero exposure to early, prolonged high‐dose indomethacin. The proposita was the second of twin girls born at 36 weeks of gestation. Pregnancy was complicated initially by polyhydramnios in both amniotic sacs and premature uterine contraction. After administration of indomethacin and terbutaline from 16 to 30 weeks' gestation, serial prenatal ultrasound examinations ultimately showed oligohydramnios in twin B and resolution of polyhydramnios in twin A. On day 5 twin B developed hematuria, hypertension, renal failure, hyponatremia, hyperkalemia, metabolic acidosis, sodium wasting and severe, transient inability to excrete potassium. Renal sonography showed enlarged, hyperechoic kidneys with almost no corticomedullary differentiation. Renal biopsy revealed immature glomeruli, dilated Bowman's spaces, dilated tubules, and interstitial fibrosis. The liver was histologically normal.

Indomethacin may induce oligohydramnios and transient renal insufficiency in humans and renal dysgenesis in fetal monkeys; it might have induced the abnormalities in this patient.
Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Stanford lipid research clinics family study
Authors: Rice Treva , Vogler George P. , Laskarzewski Peter M. , Perry Tammy S. , Rao D. C.
Published: June 2005

We examined the familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high‐density lipoprotein cholesterol (HDL) and low‐density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Stanford Lipid Research Clinics Family Study. Nonrandom probands were selected because their lipid levels at a prior screening visit exceeded a certain prespecified threshold. The statistical method is based on selection through indirect truncation on a correlated trait (in which the likelihood function is conditioned on the actual event that the proband's value is beyond the threshold). This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. The results suggest that the multifactorial transmission is homogeneous in the random and hyperlipidemic samples for CH. However, the evidence for heterogeneity is moderate for LDL, marked HDL, and mixed for TG. The general pattern of observed results is for somewhat higher genetic heritabilities in the random than nonrandom samples, which is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias associated with nonelevated lipids. Substantial genetic heritability is found for CH, HDL, and LDL, with somewhat lower estimates for TG. Cultural heritability is low but significant for all four traits. Little or no spouse resemblance or nontransmitted shared sibship effects are seen. In contrast to the findings from previous studies, little or no parental cultural transmission is seen.
Two forms of ring 13 in a child with rhabdomyosarcoma
Authors: Voullaire Lucille E. , Petrovic Vida , Sheffield Leslie J. , Campbell Peter
Published: June 2005

Mosaicism for two forms of ring 13 was found in a child with embryonal rhabdomyo‐sarcoma of the bladder, minor anomalies, and developmental delay. Her chromosome constitution was 46, XX, r(13)(p11q34)/46, XX, r del(13)(p11q14). Both cell lines were present in lymphocytes and fibroblasts. The cell line with the smaller ring chromosome predominated in both tissues. The child's manifestations reflect the presence of both cell lines.
Deletion mapping of a retinal cone‐rod dystrophy: Assignment to 18q211
Authors: Warburg Mette , Sjö Ole , Tranebjaerg Lisbeth , Fledelius Hans C.
Published: June 2005

Deletion of 18q211 was observed in a mentally retarded young man with electrophysiologically demonstrated cone‐rod dystrophy, present since childhood. He had hypogonadism and a central postsynaptic hearing impairment. This is the first case of a chromosome deletion in a patient with a cone‐rod dystrophy.

Three patients with more distal deletions on chromosome 18 did not present retinal dystrophies. We suggest that one of the loci for cone‐rod dystrophy may be located on chromosome 18 at q211‐213. Reports of similar findings will be necessary for confirmation of this assumption.
Using log‐linear models to test for associations among congenital malformations
Authors: Beaty T. H. , Yang P. , Khoury M. J. , Harris E. L. , Liang K. Y.
Published: June 2005

Log‐linear models can be used to test for pairwise associations and higher order interactions among anatomically distinct birth defects or congenital malformations. A loglinear model, including terms for every possible pairwise association among seven severe and easily detectable congenital malformations, was examined using data on 16,217 infants registered in the Metropolitan Atlanta Congenital Defects Program between 1968 and 1986. The resulting model showed clear patterns of strong association between some congenital malformations and not others, and the presence of 3‐way interaction terms where the association between two malformations depended on the presence of a third. Examining a more parsimonious log‐linear model showed overlapping patterns of pairwise association involving anal‐rectal atresia and omphalocele, anal‐rectal atresia and limb deficiency, and anal‐rectal atresia and tracheaesophageal fistula. A second common pattern involved a triangular cluster with a hierarchical relationship among the three malformations (where there was a strong association between the first and second malformations and between the first and third malformations, but the association between the second and third was only seen in the absence of the first). Three such overlapping triangular clusters were identified from these data: neural tube defects, oral clefts, and omphalocele; neural tube defects, oral clefts, and limb deficiency; and limb deficiency, diaphragmatic hernia, and neural tube defects. Some of these clusters correspond to known associations, but log‐linear models offer a simple and systematic approach to searching for possible associations among anatomically distinct malformations.
Distribution of aneuploidy in human gametes: Comparison between human sperm and oocytes
Authors: Martin Renée H. , Ko Evelyn , Rademaker Alfred
Published: June 2005

The frequency and distribution of aneuploidy was compared in 11,615 karyotyped human sperm and 772 karyotyped human oocytes to determine if all chromosomes are equally likely to be involved in aneuploid events or if some chromosomes are particularly susceptible to nondisjunction. The frequency of hypohaploidy and hyperhaploidy was compared among different chromosome groups and individual chromosomes for human sperm and oocytes. In general, hypohaploid chromosome complements were more frequent than hyperhaploid complements in sperm and oocytes. The distribution of chromosome loss in the hypohaploid complements indicated that significantly fewer of the large chromosomes and significantly more of the small chromosomes were lost, suggesting that technical loss predominantly affects small chromosomes. A conservative estimate of aneuploidy (2 X hyperhaploidy) was approximately 3–4% in the human sperm and 18–19% in human oocytes. All chromosome groups were represented among hyperhaploid human sperm and oocytes. For human sperm, the observed frequency of hyperhaploidy equaled the expected frequency based on the assumption that the frequency of nondisjunction is equal for all chromosome groups, with two exceptions: group G and the sex chromosomes. Among individual chromosomes in human sperm, chromosomes 1 and 21 and the sex chromosomes had a significant excess of hyperhaploidy. For human oocytes, there were fewer hyperhaploid oocytes than expected for chromosome groups C and F and more than expected for chromosome groups D and G. Among individual chromosomes there was a significant excess for chromosome 21. These results indicate that all chromosomes are susceptible to nondisjunction but that chromosome 21 is particularly prone to aneuploidy in both human sperm and oocytes. They also demonstrate that sex chromosome aneuploidy is common in human sperm but not in human oocytes.
Penta X syndrome: A case report with review of the literature
Authors: Kassai R. , Hamada I. , Furuta H. , Cho K. , Abe K. , Deng H.‐X. , Niikawa N.
Published: June 2005

We describe a 6 month‐old girl with a 49, XXXXX chromosome constitution. The patient had a characteristic round face, a low hairline, hypertelorism, epicanthus, a long philtrum, high‐arched palate, short and webbed neck, small hands and feet, clinodactyly of the fifth fingers, overlapping toes, and separation between the first and the second toes. She also had atrial septal defect and patent ductus arteriosus complicated by myocarditis which exacerbated the course of her congestive heart failure. Psychomotor development was retarded with opisthotonoid posture, axial hypotonia, and with a borderline abnormal EEG. A densitometric, transmission analysis on X‐linked polymorphic DNA‐fragments of the Southern blots of the patient and the parents, using P20/MspI and pERT87‐1/XmnI as probe/enzyme combinations, showed that the pentasomy X had resulted from 3 successive nondisjunctions at maternal meiosis. Clinical manifestations among 22 previously reported penta X syndrome patients are also reviewed.
Alagille syndrome associated with caudal dysplasia sequence
Authors: Rodríguez José Ignacio , Rivera Teresa , Palacios José
Published: June 2005

A 36 day‐old male with typical features of Alagille syndrome presented at birth additional features consistent with the diagnosis of caudal dysplasia sequence: imperforate anus, rectourethral fistula, lumbosacral abnormalities, and dysplastic right kidney. The association of these 2 conditions has not been previously reported, and could indicate the existence of an axial mesodermal dysplasia, of variable extension, in the Alagille syndrome.
Metacarpophalangeal pattern profiles: Q‐score for ages from birth to 7 years
Authors: Dijkstra Piet F. , Venema Henk W.
Published: June 2005

The metacarpophalangeal pattern profile (MCPP) analysis is a widely used method of standardization of bone length measurements to quantify congenital skeletal dysplasia of the hands.

A main source of inaccuracy is the prominent scatter in the values of the standard deviation (S.D.) of the reference length, which is used in the calculation of the standardized values (Z‐scores).

Other sources of error, especially when bone length measurements of younger children are evaluated, are the rather large variability in the age of appearance of the epiphyses of the different bones, and the use of tabulated reference data which are available only at one‐year intervals.

We have devised another method of standardization of bone length measurements, by calculating the Q‐score. Its advantages are that no S.D. values are needed and that more accurate results are obtained. Moreover the interpretation of the Q‐scores is more straightforward than the interpretation of the Z‐scores. Q‐scores for 3 patients with Sotos syndrome are presented.

Use of the MCPP in the form of the Q‐score, will probably make it an even stronger tool than before.
Osteodysplastic variant of primordial dwarfism
Authors: Shebib Souheil , Hugosson Claes , Sakati Nadia , Nyhan William L.
Published: June 2005

A patient with intrauterine growth retardation and marked postnatal retardation of growth had microcephaly and the orofacial and dental characteristics of the Seckel phenotype. In addition she had short forearms, metaphyseal flare, especially of the distal femora, triangular distal femoral epiphyses, and pseudoepiphyses of the hands, all characteristics of an osteodysplastic variant. Parental consanguinity suggests autosomal recessive inheritance.
New Syndrome? Robin sequence with facial and digital anomalies in two half‐brothers by the same mother
Authors: Chitayat David , Meunier Catherine M. , Hodgkinson Kathy A. , Azouz Michel E.
Published: June 2005

Two half‐brothers by the same mother presented with the Robin sequence and facial and digital anomalies. The mother has a normal face and mild hyperopia without abnormality on radiographs of the hands, feet, and pelvis. The older son is 4 years and the younger is 6 months old. Both have normal psychomotor development. To the best of our knowledge this familial association has not been reported before and probably represents a previously unrecognized heritable malformation syndrome. The occurrence of the syndrome in 2 half‐brothers by the same unaffected mother suggests X‐linked recessive inheritance.
Animal model: Chromosomal fragile site expression in dogs: II. Expression in boxer dogs with mast cell tumors
Authors: Stone Diana M. , Jacky Peter B. , Prieur David J.
Published: June 2005

Peripheral blood lymphocytes from boxer dogs with a history of cutaneous mast cell tumors were cultured for fragile site expression. As in a control group of dogs, cells from these dogs expressed folate‐sensitive autosomal and X chromosome fragile sites. Cells from boxer dogs with mast cell tumors expressed the same three common fragile sites on the X chromosome as cells from control dogs. Three folate‐sensitive autosomal fragile sites not observed in cells from the control dogs were identified in cells from boxers with mast cell tumors. These included fragile sites near the telomeres of the arms of chromosomes 3 and 4 and a fragile site on the distal half of chromosome 15. Cells from boxers with mast cell tumors showed a greater frequency of fragile site expression than did cells from control dogs, but this observation was attributed to an unintended selection bias for younger boxer dogs without mast cell tumors and older boxer dogs with mast cell tumors and an increased frequency of fragile site expression with increasing age in dogs of the boxer breed.
Pathogenetic mechanisms of fetal akinesia deformation sequence and oligohydramnios sequence
Authors: Rodríguez José Ignacio , Palacios José
Published: June 2005

This article briefly reviews the participation of fetal compression, muscular weakness, and fetal akinesia in the genesis of the anomalies found in fetal akinesia deformation sequence (FADS) and oligohydramnios sequence (OS). Both sequences share phenotypic manifestations, such as arthrogryposis, short umbilical cord, and lung hypoplasia, in relation to decreased intrauterine fetal motility. Other characteristic manifestations found in OS, such as Potter face, and redundant skin, are produced by fetal compression. On the other hand, growth retardation, craniofacial anomalies, micrognathia, long bone hypoplasia, and polyhydramnios found in FADS could be related to intrauterine muscular weakness.
Baller‐Gerold syndrome associated with congenital hydrocephalus
Authors: Lewis M. E. Suzanne , Rosenbaum Peter L. , Paes Bosco A.
Published: June 2005

We present a new case of the Baller‐Gerold syndrome (BGS) in an infant with prenatally apparent severe hydrocephalus, growth retardation, and cardiac and limb abnormalities detected by ultrasound at 26 weeks of gestational age. Subsequent survival to term and neonatal examination confirmed an unsuspected diagnosis of BGS.
Father‐to‐daughter transmission of focal dermal hypoplasia associated with nonrandom X‐inactivation: Support for X‐linked inheritance and paternal X chromosome mosaicism
Authors: Gorski Jerome L.
Published: June 2005

Focal dermal hypoplasia (FDH) is a rare syndrome of severe developmental anomalies of the tissues and organs derived from ectoderm and mesoderm. Though data have suggested that FDH is an X‐linked dominant trait associated with male hemizygote lethality, a hypothesis supported by the observation of three unrelated infants with FDH manifestations andde novochromosome rearrangements involving Xp22, observations of father‐to‐daughter transmission have suggested possible genetic heterogeneity and autosomal dominant inheritance with sex limitation. We hypothesize that, if FDH is an X‐linked disorder, cells expressing an active disease locus might experience a selective disadvantage resulting in a nonrandom pattern of X‐inactivation in patient tissue. To test this hypothesis, we studied one of the two previously described families demonstrating father‐to‐daughter inheritance of FDH. To determine if the affected daughter had a skewed pattern of X‐inactivation consistent with X‐linked inheritance of FDH, somatic cell hybrids were constructed by fusing hypoxanthine phosphoribosyl transferase (HPRT)‐deficient rodent fibro‐blasts with either patient dermal fibroblasts or peripheral white blood cells (WBCs); hybrid clones retaining an active X chromosome were analyzed to determine the parental origin of the active X chromosome. Analyses of resulting hybrid clones showed that while hybrids constructed from skin fibroblasts contained an active X chromosome inherited from either of the patient's parents, hybrids constructed from WBCs showed a skewed pattern of X‐inactivation; 11 of 11 hybrids contained an active maternal X chromosome (X2= 12.2,P= .001). These findings indicated that, in this family, FDH was associated with a nonrandom pattern of X‐inactivation consistent with X‐linked inheritance, suggesting that the patient's father was mosaic for a mutant FDH allele.
Reduced activity of arylsulfatase A and predisposition to neurological disorders: Analysis of 140 pediatric patients
Authors: Sangiorgi Simonetta , Ferlini Alessandra , Zanetti Adele , Mochi Mirella
Published: June 2005

A sample of 140 children exhibiting neurologic disturbances (93 suffering from epilepsy and 47 with delayed psychomotor development or mental retardation) was tested for the activity of some lysosomal enzymes. A partial deficiency of arylsulfatase A (ASA) in leucocytes (activities lower than 60% of the control average) was detected in 36 patients (25.7%), whereas few ASA‐deficient individuals (1.4%) were found in the control sample of 71 healthy children. Therfore, the frequency of ASA deficiency is abnormally high in our sample of pediatric patients. ASA activity levels were also assayed on fibroblasts from 12 of the 36 ASA‐deficient patients; the mean activity in these cells was 20% of the control average. Excretion of urinary sulfatides was not in creased in the tested ASA‐deficient patients (10/36). Clinical symptoms of these ASA‐deficient patients bore no resemblance to classical metachromatic leucodystrophy (MLD), but resemble literature cases labeled as atypical MLD or diagnostic puzzles. This result suggests that reduced ASA activity might be associated with an increased risk of developing neurologic or neuropsychiatric disturbances in children.
Balanced complex chromosomal rearrangements with more than four breakpoints: Report of a new case
Authors: Till Marianne , Devillard Françoise , Crost Pierre , Bachy Monique , Prieur Fabienne , Berthéas Marie‐Françoise
Published: June 2005

Congenital complex chromosomal rearrangement (CCR) compatible with life are rare in man. We report on a new case of apparently balanced CCR in a 30‐month‐old boy with mental retardation and minor anomalies.

This CCR consists in a 3‐way reciprocal translocation (2;3;16) and an insertion (6;7), as it was analyzed by different banding and high resolution techniques.

It involves 6 breakpoints: 2q11, 13q12, 16p11, 6p21.3, 7q21.3 and 7q35.
New X‐linked syndrome of mental retardation, gynecomastia, and obesity is linked to DXS255
Authors: Wilson Meredith , Mulley John , Gedeon Agi , Robinson Hazel , Turner Gillian
Published: June 2005

We describe 14 males from 3 successive generations in a family who have X‐linked mental retardation (XLMR), obesity, gynecomastia, speech difficulties, emotional lability, tapering fingers, and small feet. Linkage analysis using markers spread along the X chromosome demonstrated a gene localisation close to the centromere. Maximum lod scores for markers near the centromere, all at θ= 0.00, were 1.36 for DXS7, 4.82 for DXS255, 2.79 for DXS14, 2.09 for DXS72, and 1.46 for DXYS1. The closest flanking markers which showed recombination were DXS84, and DXS94, defining the physical localisation within Xp21.1‐q22. DXS255 was fully informative with lod‐1 confidence interval for θ of 0.00–0.12. Clinical findings and linkage data in this family distinguish it from the Börjeson‐Forssman‐Lehmann syndrome and other previously described XLMR syndromes.
Blepharophimosis sequence and de novo balanced autosomal translocation [46, XY,t(3;4)(q23;p15.2)]: Possible assignment of the trait to 3q23
Authors: Fukushima Yoshimitsu , Wakui Keiko , Nishida Toshiro , Ueoka Yasuo
Published: June 2005

We report on a boy with the blepharophimosis sequence and de novo, apparently balanced reciprocal translocation between 3q23 and 4p15.2 [46, XY,t(3;4)(q23;p15.2)de novo]. Possible assignment of this autosomal dominant disorder is discussed. A 3q23 band is a more preferable gene locus of the blepharophi mosis sequence, based on the comparison of clinical manifestations between 4p‐ and 3q‐syndromes.
Amber mutation creates a diagnostic MaeI site in the androgen receptor gene of a family with complete androgen insensitivity
Authors: Trifiro Mark , Prior R. Lynn , Sabbaghian Nelly , Pinsky Leonard , Kaufman Morris , Nylen Edward G. , Belsham Denise D. , Greenberg Cheryl R. , Wrogemann Klaus
Published: June 2005

We have discovered in the X‐linked androgen receptor gene a single nucleotide substitution that is the putative cause of complete androgen insensitivity (resistance) in a family with affected individuals in 2 generations. Earlier studies on the family indicated cosegregation of mutant phenotype and the RFLPs at the loci DXS1 and DXYS1. The mutation is an adenine‐to‐thymine transversion in exon 8 that changes the sense of codon 882 from lysine to an amber (UAG) translation termination signal. The substitution creates a recognition sequence for the restriction endonuclease MaeI: this permits ready recognition of hemizygotes and heterozygotes after amplification of genomic exon 8 by the polymerase chain reaction. The mutation predicts the synthesis of a truncated receptor that lacks 36 amino acids at the carboxy terminus of its 252‐amino acids androgen‐binding domain. The cultured genital skin fibroblasts of the one affected patient examined have normal levels of androgen receptor mRNA, but negligible androgen‐receptor binding activity. These results accord with a variety of data from spontaneous and artificial mutations indicating that all portions of the steroid binding domain contribute to normal steroid binding by a steroid receptor.
Syndrome of mental retardation and distal arthrogryposis in sibs
Authors: Chitayat David , Hodgkinson Kathy A. , Blaichman Shirley , Chen Moy‐Fong , Watters Gordon V. , Khalife Samir , Hall Judith G.
Published: June 2005

Two sisters presented with a syndrome of characteristic facial anomalies and distal arthrogryposis. The older sister is now 4 years old and is severely mentally retarded. Her sister died of respiratory failure due to hypoplastic lungs shortly after birth. The occurrence of this potentially lethal syndrome in 2 sisters with unaffected parents suggests autosomal recessive inheritance.
Molecular study of the Prader‐Willi syndrome: Deletion, RFLP, and phenotype analyses of 50 patients
Authors: Hamabe Jun‐Ichi , Fukushima Yoshimitsu , Harada Naoki , Abe Kyohko , Matsuo Nobutake , Nagai Toshiro , Yoshioka Akira , Tonoki Hidefumi , Tsukino Ryuichi , Niikawa Norio
Published: June 2005

Deletion and RFLP studies with 5 cloned DNA markers localized at 15q11.2 were performed in 50 patients with the Prader–Willi syndrome (PWS). A one‐copy density (deletion) for at least one of 4 loci, D15S9, D15S11, D15S10, D15S12, was detected in 32 (64%) of the 50 patients; deletions of each of the 4 loci were found in 29, 30, 29, and 28 patients, respectively. Three patients showed 4 or more copy density for D15S12 locus, in addition to deletions. The remaining 18 patients showed two‐copy densities for each of the 4 loci. A common site of rearrangements among our 32 patients as well as the reported patients seemed to be confined to a segment between D15S9 and D15S11, suggesting the putative PWS gene locus in this segment. Of 6 patients who have cytologic deletions but did not show any molecular deletions, 3 have normal size of hands and feet, and 4 have normally pigmented skin and hair. The normal pigmentation was also observed in 3 patients who had small molecular deletions in the examined 5‐locus segment. These observations may support the conception of contiguous gene syndrome. RFLP analysis demonstrated maternal uniparental isodisomy of chromosomes 15 in both a patient with 45,t(15q;15q) and a karyotypically normal patient. Based on the results of the present study, a new model is proposed to explain the occurrence of PWS with a variety of chromosome abnormalities, including partial monosomy, disomy, trisomy, and/or tetrasomy for 15q11.2. The normal development may require an even or more “number ratio” of paternally derived allele(s) to maternally derived allele(s) of the gene(s) localized at 15q11.2, and a disturbance of the ratio would lead to the PWS phenotype.
DNA deletion and its parental origin in Angelman syndrome patients
Authors: Hamabe Jun‐Ichi , Kuroki Yoshikazu , Imaizumi Kiyoshi , Sugimoto Tateo , Fukushima Yoshimitsu , Yamaguchi Atsuko , Izumikawa Yoshinori , Niikawa Norio
Published: June 2005

DNA deletion studies using 5 DNA markers localized at 15q11–q12 were performed in 14 Angelman syndrome (AS) patients (9 sporadic and 5 familial cases). A one‐copy density for one or more of the 5 loci was detected in 8 (57.1%) of the 14 patients. A deletion of only the D15S11 locus was detected in one sporadic patient, that involving only the D15S10 in 3 familial patients (sibs in a family), that spanning 3 loci (D15S11, D15S10, D15S12) in one sporadic patient, and that spanning 4 loci (D15S9, D15S11, D15S10, D15S12) in the other 3 sporadic patients. The deletion common to our patients as well as to the reported patients may be confined to a segment between D15S11 and D15S10, if the 5 loci are ordered as cen‐D15S18‐(D15S9‐D15S11‐D15S10)‐D15S12‐qter. This site overlaps but is more distal to the common deletion site in Prader‐Willi syndrome (PWS) patients. In the family of the 3 sibs, both of the phenotypically normal mother and maternal grandfather also have deletions of the D15S10 locus. These results were consistent with the genomic imprinting hypothesis for the occurrence of AS, i.e., the lack of a maternally derived locus leads to AS, but may not support a model that AS is the alternative phenotype of PWS at the identical locus.
Costello syndrome
Authors: Der Kaloustian Vazken M. , Moroz Brenda , McIntosh Nathalie , Watters A. Kevin , Blaichman Shirley
Published: June 2005

In 1971, Costello described a new syndrome in 2 patients. The major clinical findings comprise short stature; redundant skin of the neck, palms, soles, and fingers; curly hair; relative macrocephaly; depressed nasal bridge; papillomata around the mouth and nares; distinct facial gestalt; hyperextensible joints; and mental retardation. We present a third patient and review the manifestations of this condition.
Monozygotic twins discordant for Ullrich‐Turner syndrome
Authors: Kaplowitz Paul B. , Bodurtha Joann , Brown Judith , Spence J. Edward
Published: June 2005

We describe 9‐year‐old twin girls who were thought to be monozygotic but who differed greatly in physical appearance and growth pattern. One twin had Ullrich‐Turner syndrome (UTS),45,X/46,XX mosaicism in peripheral blood, and only 45,X cells in skin fibroblasts. The phenotypically normal twin also had 45,X/46,XX mosaicism in blood but only 46,XX cells in cultured fibroblasts. Analysis of DNA marker patterns in blood lymphocytes and in skin fibroblasts confirmed monozygosity with a probability of 99.97%. This case is compared with other reported cases of discordance for UTS in twins. It is concluded that essentially all of the differences between the two twins can be explained by loss of an X chromosome early in embryogenesis with complete separation of 45,X and 46,XX cell lineages at the time of the twinning event. The presence of mosaicism in the peripheral blood of both twins is presumably due to anastomoses between the placentae resulting in a mixture of the two cell populations in the hematopoietic tissue.
Glutaric aciduria type I: A common cause of episodic encephalopathy and spastic paralysis in the Amish of Lancaster County, Pennsylvania
Authors: Morton D. Holmes , Bennett Michael J. , Seargeant Lorne E. , Nichter Charles A. , Kelley Richard I.
Published: June 2005

We have diagnosed type I glutaric aciduria (GA‐I) in 14 children from 7 Old Order Amish families in Lancaster County, Pennsylvania. An otherwise rare disorder, GA‐I appears to be a common cause of acute encephalopathy and cerebral palsy among the Amish. The natural history of the disease, which was previously unrecognized in this population, is remarkably variable and ranges from acute infantile encephalopathy and sudden death to static extrapyramidal cerebral palsy to normal adult. Ten patients first manifested the disease between 3 and 18 months at the time of an acute infectious illness. Four of these children died in early childhood, also during acute illnesses. However, there has been little progression of the neurological disease after age 5 years in the surviving children and intellect usually has been preserved, even in children with severe spastic paralysis. When well, patients have plasma glutaric acid concentrations ranging from 4.8 to 14.2 m̈mol/liter (nl 0‐5.6 m̈mol/liter) and urinary glutaric acid concentrations from 12.5 to 196 mg/g creatinine (nl 0.5–8.4 mg/g creatinine). We have found that GA‐I can be diagnosed in the Amish by measurement of urinary glutaric acid concentrations using isotope‐dilution gas chromatography/mass spectrometry, whereas the diagnosis can easily be missed by routine urine organic acid gas chromatography. Based on our observations about the natural history of GA‐I in the Amish, we anticipate that, with early diagnosis afforded by GC/MS screening of individuals at risk, the combination of restriction of dietary protein and limitation of protein catabolism, dehydration, and acidosis during illnesses will prevent the onset or progression of neurological disease in Amish patients with this variant of GA‐I.
Oto‐palatal‐digital syndrome type II with X‐linked cerebellar hypoplasia/hydrocephalus
Authors: Stratton Robert F. , Bluestone Daniel L.
Published: June 2005

We describe an infant with clinically apparent oto‐palatal‐digital syndrome Type II (OPD II), who, in addition, also has hydrocephalus and cerebellar hypoplasia. This second X‐linked disorder has not been reported previously to occur in association with OPD II. This patient had 2 maternal uncles who died neonatally with congenital hydrocephalus and digital abnormalities consistent with OPD II. We suggest that these 2 entities may be located near one another on the X chromosome, and that both loci are affected in this family.
Deletion of the distal short arm of the X chromosome (Xp) in a patient with short stature, chondrodysplasia punctata, and X‐linked ichthyosis due to steroid sulfatase deficiency
Authors: Ballabio A. , Zollo M. , Carrozzo R. , Caiulo A. , Zuffardi O. , Cascioli C. F. , Viggiano D. , Strisciuglio P.
Published: June 2005

We observed a boy with short stature, chondrodysplasia punctata, ichthyosis, and a terminal deletion of Xp. Steroid sulfatase deficiency was demonstrated in the patient's fibroblasts. Molecular analysis showed a deletion of the entire steroid sulfatase gene. This case represents another example of a contiguous gene syndrome in which the co‐deletion of adjacent genes on a chromosome is responsible for a complex phenotype.
Cognitive and motor skills in achondroplastic infants: Neurologic and respiratory correlates
Authors: Hecht Jacqueline T. , Thompson Nora M. , Weir Tempa , Patchell Larry , Horton William A.
Published: June 2005

Thirteen infants with achondroplasia underwent psychometric testing as part of a comprehensive neurologic assessment. As a group, mental development was average and motor development was delayed, although a wide range of scores was obtained. Foramen magnum measurements were correlated with respiratory dysfunction, abnormal so‐matosensory evoked potentials, and delayed motor development. Abnormal polysomno‐gram outcome was associated with reduced mental capacity. In light of the reported increased frequency of respiratory dysfunction in achondroplasia, these findings warrant careful attention and further study.
Diagnostic hand anomalies in Smith–Magenis syndrome: Four new patients with del (17)(p11.2p11.2)
Authors: Kondo Ikuko , Matsuura Shinya , Kuwajima Katsuko , Tokashiki Midori , Izumikawa Yoshinori , Naritomi Kenji , Niikawa Norio , Kajii Tadashi
Published: June 2005

We report clinical and cytogenetic findings of 4 children (2 boys and 2 girls) with the Smith–Magenis syndrome. All 4 patients had an interstitial deletion of 17p: del(17) (p11.2p11.2). Their clinical manifestations included brachycephaly, midface hypoplasia, prognathism, upper lip eversion, short and broad hands with short fingers, clinodactyly of the fifth fingers, fingertip pads, moderate mental retardation, and behavior problems. Analysis of the metacarpophalangeal pattern profiles in patient 2 showed progressive shortness from the metacarpals to the proximal, middle, and the distal phalanges. The finger‐pads observed in all 4 patients have hitherto been noted in only one of 26 previously reported patients with the syndrome. These findings serve as a useful clue to the diagnosis of the syndrome.
Analysis of neocortex in three males with the fragile X syndrome
Authors: Hinton V. J. , Brown W. T. , Wisniewski K. , Rudelli R. D.
Published: June 2005

Fragile X [fraX] syndrome is a common hereditary disorder associated with a fragile site marker at Xq27.3 which clinically presents as a form of mental retardation (MR). Postmortem investigation of 3 fraX positive males with mild to moderate MR did not document any gross neuropathological changes. Golgi analysis of neocortical dendritic spine morphology extended our previous observations of immature, long, tortuous spines in one adult case of fraX (Rudelli, et al., Acta Neuropathologica 67:289–295, 1985) to 2 new cases. Evidence for similar dendritic spine abnormalities was found, although Golgi analysis was less than optimal because of incomplete dendritic stain impregnation. Neocortical intra‐layer cell density was also investigated in all 3 cases. Cresyl violet stained neurons were counted in 10 randomly selected fields in neocortical layers II–VI of cingulate and temporal association areas (Brodmann's areas 23 and 38). Neuron counts in fraX and control neocortex showed no significant differences. Thus, abnormal dendritic spine morphology with preservation of neuronal density appears to characterize the neocortex in individuals with this common form of mental retardation.
Syndrome of developmental retardation, facial and skeletal anomalies, and hyperphosphatasia in two sisters: Nosology and genetics of the coffin‐siris syndrome
Authors: Rabe Petra , Haverkamp F. , Emons D. , Rosskamp R. , Zerres K. , Passarge E.
Published: June 2005

We report on 2 sisters, 3 and 6 years old, with a possible new syndrome consisting of developmental retardation, facial and skeletal anomalies, and hyperphosphatasia. This disorder closely resembles the Coffin–Siris syndrome (McKusick number 135900). We describe the difficulties in achieving a diagnosis. A major diagnostic clue was the radiological recognition of hypoplasia/aplasia of the terminal phalanx of the 5th finger. Minor facial anomalies and mental retardation alone had not led to the proper diagnosis. Still, several diagnostic possibilities remain. For unknown reasons both children have an increased level of serum alkaline phosphatase activity.
Angular homeostasis VIII. Pursuit of a slowly moving target in a plane: Relevance to lateralization in cardiovascular ontogeny
Authors: Murphy Edmond A. , Rhee Sonia , Pyeritz Reed E. , Berger Kenneth R.
Published: June 2005

We explore the pursuit in a plane of a target moving at constant slow speed in a straight line. Two models of the pursuit are given. In the continuous case, the pursuer is moving at constant speed and is subject to proportionate angular homeostasis with correction constant b. In the discrete version movement occurs at a constant speed in a sequence of straight line segments of constant length (called the step size, s) the end of the segments being called the vertices. The pattern considered is not the absolute position of the pursuer, but its distance and orientation relative to the target. Both the transients and the asymptotic orbit are addressed. A key quantity is r, the speed of the target expressed as a fraction of that of the pursuer. If the speed of the pursuer is defined as unity, r is also the ratio of the speeds. There exists a critical speed fraction, R(b, s), a function of b and s, that defines what the term slow designates. R(b,s), which has to be found numerically, has the following property. For r < R(b, s), the asymptotic path is a simple closed curve. In the discrete case the vertices converge to a simple closed curve. The larger r, the more the path (or in the discrete analogue its set of vertices) departs from a circle, and the more eccentric the target is with respect to it. Interest centers on two issues. First we address the transient patterns of the path, notably whether or not the sense of any particular path (clockwise or counterclockwise) is the same throughout, or changes at some stage. These studies have a bearing on ontogenetic lateralization of the viscera; its relationship to the classification of dextrocardia is addressed. Second, we considor the asymptotic form of the path and its relationship to the parameters. The critical values of R (b, s) are extensively explored.
Gardner syndrome: Study and follow‐up of a family
Authors: Kratzer Guy L. , Kasumi Asao , Krush Anne J.
Published: June 2005

A study is in progress of a family (Family P) with Gardner syndrome (familial adenomatous polyposis with extraintestinal manifestations—FAPG). Occult bone lesions of the jaws and ocular fundus lesions were found in a number of affected and at‐risk relatives. In some, these “markers” were found early in life before the appearance of colonic polyps. Family P is remarkable for differences in expression of the gene manifested by differences in the age‐at‐onset of polyps of the colon, in number and size of polyps, and in occurrence of desmoids. These differences may explain why some at‐risk relatives wisely followed medical surveillance plans while others, who lacked symptoms, failed to do so. Others without medical guidance undertook their own independent “treatment.”

As knowledge about extracolonic lesions has increased and surgical treatment for FAPG improved from the time the first affected member of Family P received her diagnosis in 1953, the outlook for survival has also improved. Family communication and that among professionals treating families with FAPG may be improved as worldwide Polyposis Registries increase in number. The risk of postsurgical extraintestinal complications is reason enough to urge life‐long medical surveillance for all at‐risk relatives.
Apparently new MCA/MR syndrome in sibs with cleft lip and palate and other facial, eye, heart, and intestinal anomalies
Authors: Kapur S. , Toriello H. V.
Published: June 2005

We report on a sister and brother with severe mental retardation, bulbous tip of the nose, long columella, cleft lip and palate, heart and intestinal anomalies, and growth retardation. This appears to be a previously unreported, autosomal recessive condition, given high resolution prometaphase chromosomes are normal.