bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome 10qter deletion syndrome: A review and report of three new cases
Authors: Wulfsberg Eric A. , Weaver Ramona P. , Cunniff Christopher M. , Jones Marilyn C. , Jones Kenneth Lyons
Published: June 2005

We report on three patients with terminal deletions of chromosome l0q and compare them to 15 previously reported patients. A similar facial appearance with a prominent beaked nose, large and/or malformed ears, and a pattern of major abnormalities including severe mental retardation, cardiac anomalies, and anogenital anomalies are reviewed. We feel the manifestations of del l0qter are sufficiently distinct to suggest this diagnosis on clinical examination.
Omodysplasia
Authors: Maroteaux P. , Sauvegrain J. , Chrispin A. , Farriaux J. P.
Published: June 2005

Three cases of a new congenital bone disorder associating facial anomalies (depressed nasal bridge, broad base of the nose, long philtrum) with short humeri. The complex skeletal abnormalities consist of a defect of growth of the distal end of the humerus, a hypoplastic everted condyle, an upper radioulnar diastasis, and a anterolateral dislocation of the head of the radius. The condition is dominantly inherited.

Two other cases with the same facial anomalies and osteoarticular abnormalities of the upper limbs are described. These cases also showed a severe micromelic dwarfism due to shortness of the long bones, particularly the femora. The present authors consider that these represent variable expressivity of the same disorder and propose that this condition be called omodysplasia (from the Greek term for humerus).
Greig syndrome in a large kindred due to reciprocal chromosome translocation t(6;7)(q27;p13)
Authors: Krüger Gabriele , Götz Jürgen , Kvist Ulrich , Dunker Helmut , Erfurth Fritz , Pelz Lothar , Zech Lore
Published: June 2005

We report on cases of Greig syndrome segregating in a large kindred over four generations due to reciprocal translocation t(6;7)(q27;p13) and on a patient from this pedigree with a severe malformation syndrome due to duplication 7(pl3→pter). The clinical findings are discussed as possible consequence of a gene mutation due to the break at 7pl3.
Megalocornea and mental retardation syndrome: A new case
Authors: Grønbech‐Jensen Michael
Published: June 2005

We report on a new case of the megalocornea mental retardation syndrome, first described by Neuhäuser et al. [1975]. Our patient had mental and motor retardation, megalocorneae, short stature, congenital hypotonia, frontal bossing, micrognathia, a cafe‐au‐lait spot, and ear anomalies. A literature survey is provided.
Skeletal dysplasia syndrome with progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes: A variant example of the Lenz–Majewski syndrome
Authors: Chrzanowska K. H. , Fryns J. P. , Krajewska‐Walasek M. , Van den Berghe H. , Wisniewski L.
Published: June 2005

Here we report a 10 year‐old mentally retarded, deaf boy with a unique pattern of anomalies: progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes. He represents a variant example of “hyperostotic dwarfism” as delineated by Lenz and Majewski.
Prevalence of lethal osteochondrodysplasias in Denmark
Authors: Andersen Poul Erik
Published: June 2005

The point prevalence at birth of lethal osteochondrodysplasias in a subregion of Denmark was estimated by a study of all children born January 1970 through December 1983. Two cases of thanatophoric dysplasia, one case of thanatophoric dysplasia with cloverleaf skull, two cases of micromelic bone dysplasia with cloverleaf skull, two cases of achondrogenesis type III, and three cases of achondrogenesis type IV were found. Two cases were unclassifiable due to lack of radiographs. In total, the point prevalence at birth was 15.4 per 100,000. Thus lethal Osteochondrodysplasias seem to be more common than is generally assumed.

The clinical and radiographic findings in micromelic bone dysplasia with cloverleaf skull are discussed in relation to thanatophoric dysplasia and achondrogenesis type IV.
Confirmation of prenatal diagnosis of sex chromosome mosaicism
Authors: McFadden D. E. , Kalousek D. K.
Published: June 2005

Prenatal diagnosis of mosaicism causes problems in interpretation and in genetic counselling. Part of the difficulty with any prenatal diagnosis of mosaicism is interpretation of results without knowing the exact origin, embryonic or extraembryonic, of the abnormal cell line. To confuse the issue in cases of prenatal diagnosis of 45,X/46,XY mosaicism is the recent demonstration that a diagnosis of 45,X/46,XY made prenatally is not necessarily associated with the same phenotype as when diagnosed postnatally.

We present two cases of prenatal diagnosis of sex chromosome mosaicism (45,X/46,XY and 45,X/47,XYY). Posttermination examination of the phenotypically normal male fetuses and their placentas established that the placenta was the most likely source of the 45,X cell line. An approach to confirming the prenatal diagnosis of sex chromosome mosaicism and establishing its origin utilizing detailed cytogenetic examination of both fetus and placenta is suggested.
Prenatal diagnosis of a large heteromorphic region in a chromosome 5: Implications for genetic counseling
Authors: Fineman Robert M. , Issa Bonnie , Weinblatt Vivian
Published: June 2005

We performed an amniotic fluid chromosome study at 16 weeks of gestation because of advanced maternal age. G‐band chromosome analysis demonstrated that one 5q was significantly longer than its homologue. The region subjacent to the centromere appeared similar to a 9qh region. Subsequent Giemsa‐11 and C‐band staining results of this area were positive. Cytogenetic studies in this family demonstrated several other individuals who have the same chromosome 5qh+ as the proposita. All are asymptomatic. The clinical insignificance of the chromosome heteromorphism in this family readily demonstrates the need for special cytogenetic and family chromosome studies before performing genetic counseling.
Interstitial deletion of the proximal long arm of chromosome 4 associated with father‐child incompatibility within the Gc‐ system: Probable reduced gene dosage effect and partial piebald trait
Authors: Yamamoto Yoshifumi , Nishimoto Hiroshi , Ikemoto Shigenori
Published: June 2005

Gc‐system typing by isoelectric focusing polyacrylamide gel electrophoresis and quantitative assays were carried out on a patient with a karyotype of 46,XY,del(4)(q12q21.1) and on his parents with normal chromosomes. Although a father‐child incompatibility within the Gc‐system suggested that its locus is on segment 4q12‐13, the serum concentration of vitamin D binding protein in the patient and his father were only about half of that of his mother and control individuals. The possibility of interference of a silent allele in the child could not be excluded. Associated congenital partial leukodermia appeared to be an expression of a partial piebald trait.
Somatic and intellectual development in a patient with 47,XX,psu dic(X)(p11.2) chromosome constitution
Authors: Ocrant Ian , Bangs Charles D. , Johnston Kathreen M. , Wilson Darrell M. , Hintz Raymond L. , Rosenfeld Ron G. , Donlon Timothy A.
Published: June 2005

An unusual form of X chromosome aneuploidy, 47,XX,psu dic(X)(p11.2), was found during an evaluation for short stature of a prepubertal girl. Unlike 45,X, 47,XXX, 48,XXXX, and 49,XXXXX females, this patient is phenotypically normal except for her short stature, which appears to be unrelated to her chromosome abnormality. X chromosome inactivation studies disclosed inactivation (late replication) of one normal X and the abnormal X chromosome in all cells examined from this patient. Therefore, she is disomic for early‐replicating distal Xp loci, found in inactivated X chromosomes, and thought to remain active after lyonization. These data suggest that the presence of three or more copies of the early‐replicating, active Xp loci may be responsible for the cognitive deficits and other phenotypic abnormalities seen in polysomy X females.
Restriction fragment length polymorphisms within proximal 15q and their use in molecular cytogenetics and the Prader‐Willi syndrome
Authors: Nicholls Robert D. , Knoll Joan H. , Glatt Karen , Hersh Joseph H. , Brewster Thomas D. , Graham John M. , Wurster‐Hill Doris , Wharton Robert , Latt Samuel A.
Published: June 2005

Restriction fragment length polymorphisms (RFLPs) are described in detail for 6 DNA probes (D15S9–13, D15S18) that localize to the proximal long arm of human chromosome 15 (15q11–15q13: this report and Tantravahi et al., Am. J. Med. Genet. 33:78–87. Multiple RFLPs are detected by the probe that identifies locus D15S13, and these RFLPs are shown by genomic mapping to result from a nearby insertion or deletion of 1.8 kilobases (kb) of DNA. This set of RFLPs detected by proximal 15q probes can be used for studies on the Prader‐Willi syndrome (PWS) and on mentally retarded individuals with a supernumerary inv dup(15) chromosome. Five of the polymorphic loci (D15S9–13) map to the region implicated in the cause of the PWS (15qll.2–15q12). Each of 4 families tested with these probes, as well as an additional “PWS‐like” patient, was informative by RFLP analysis. The two PWS deletions studied, which occurred de novo, were inherited from the chromosome 15 provided by the father. By contrast, the 2 inv dup(15) chromosomes analyzed were of maternal origin. The use of RFLPs can also simplify the molecular determination of copy number in chromosomal aneuploidy, as exemplified by analysis of individuals with the PWS and a deletion, patients with an inv dup(15), and one patient with a more complex rearrangement involving chromosome 15. Our studies demonstrate the application of DNA probes for both molecular cytogenetic studies on this chromosome region and the development of diagnostic molecular markers to aid early clinical diagnosis of the PWS.
Alagille syndrome associated with Moyamoya disease
Authors: Rachmel Avinoam , Zeharia Avraham , Neuman‐Levin Margalit , Weitz Raphael , Shamir Raanan , Dinari Gabriel
Published: June 2005

A 22‐month‐old girl with the typical manifestations of Alagille syndrome presented with acute right hemiparesis. Cerebral angiographic studies demonstrated the presence of complete occlusion of both internal carotid arteries with the formation of a collateral network of vessels compatible with the diagnosis of Moyamoya disease. This rare association has not been reported previously.
Molecular diagnosis of the fragile X [Fra (X)] syndrome: Calculation of risks based on flanking DNA markers in small phase‐unknown families
Authors: Bridge Peter J. , Lillicrap David P.
Published: June 2005

We studied two small, two‐generation families with the fragile X [Fra (X)] syndrome. The absolute phase of the DNA markers in relation to the disease in the mother was not known in either family. We present the derivation of risks for these families using flanking markers, taking into account the uncertainty regarding maternal phase. Since the use of flanking markers fails to yield useful counseling data in the ⅓ to ½ of all cases where a single recombination event occurs between the two flanking markers, we calculate the probability that this method is likely to be successful or unsuccessful when prenatal diagnosis is attempted using linked RFLPs.
Effect of framing on the perception of genetic recurrence risks
Authors: Shiloh Shoshana , Sagi Michal
Published: June 2005

Individuals asked to evaluate genetic recurrence risks were found to be influenced bythe way the risks were framed Presenting a single risk figure resulted in overweightingof low probabilities and underweighting of high probabilities, as compared to presentinga list of sequential risks. Differences werealso found between meanings attached to verbal expressions of risks when translating from verbal to numerical expressions, and vice versa. The implications of these findings for genetic counseling are discussed.
Pathogenic and nonpathogenic deletions in two families with Duchenne muscular dystrophy
Authors: Hart Kevin A. , Abbs Stephen , Bobrow Martin
Published: June 2005

Two deletions detected within the Duchenne/ Becker muscular dystrophy (D/BMD) gene of normal male members of two DMD families were both independent, nonpathogenic deletions located in a large intron in the XJ region(DXS206) toward the 5′ end of the gene [Burghes et al., 1987]. Investigation of the surrounding exons revealed no exon deletions or duplications. The simplest interpretation of these observations is that the deletions are entirely intronic and do not cause perturbation of the gene product, resulting in a normal phenotype. The disease phenotypes in the affected males in these two families are caused by exon deletions remote from this intron. Some caution is therefore indicated in using genomicdeletions for clinical prediction.
Dominant inheritance of Wiedemann‐Beckwith syndrome: Further evidence for transmission of “unstable premutation” through carrier women
Authors: Aleck Kirk A. , Hadro Teresa A.
Published: June 2005

We report on a 4‐generation family in which the Wiedemann Beckwith syndrome (WBS) was transmitted as an autosomal dominant trait. The condition occurred in sibs born to carrier women and in children born to affected mothers. Presumptive carrier women were examined for microsigns of WBS in an attempt to determine whether extreme variability of the disorder, rather than an unaffected carrier state, was present. No minor stigmata of the WBS could be found in the presumptive carriers. Our study supports a previous hypothesis that in some families the WBS can be transmitted in a 2‐step process involving first an unstable premutation and then a “telomutation.” Because only females appear to be transmitters of the telomutation, an ovum‐mediated sex‐associated factor may be involved in the process of telomutation.
Femoral duplication: A case report
Authors: Bodurtha Joann , Coutinho Maria , Benator Richard , Nogi Jay , Sholley Milton , Nance Walter E.
Published: June 2005

Femoral duplication is a rare anomaly that has been described as an isolated entity and in association with other congenital defects. Since the description by Erlich in 1885, 24 additional cases have been reported. The present report concerns a 34‐week black female infant with apparent bilateral femoral duplication associated with a meningocele and abdominal, genitourinary, vertebral, and lower‐limb anomalies. The cause is unknown. Femoral duplication is a developmental field defect, hence causally heterogeneous.
Humero‐radio‐ulnar synostosis: A new case and review
Authors: Hersh Joseph H. , Joyce Margie R. , Profumo Laura E.
Published: June 2005

We report on a patient with humero‐radio‐ulnar synostosis and upper limb oligoectrosyndactyly. All cases have been sporadic including discordance in monozygotic twins, and similar findings have occurred in thalidomide embryopathy. Further observations of similarly affected patients are needed to elucidate the nature of this upper limb defect and its cause.
Aplasia of the tibia with bifurcation of the femur and ectrodactyly: Evidence for an autosomal recessive type
Authors: Kohn Gertrude , El Shawwa Raghda , Grunebaum Michael
Published: June 2005

Two unrelated families are presented, each with 2 affected offspring with bifid femur, absent tibia, and ectrodactyly. The healthy parents are consanguineous. It is postulated that this combination of malformations is causally heterogenous with both autosomal dominant and autosomal recessive modes of inheritance; hence, it is established as a developmental field defect.
Ptosis of eyelids, strabismus, diastasis recti, hip defect, cryptorchidism, and developmental delay in two sibs
Authors: Carnevale Franco , Krajewska Grazyna , Fischetto Rita , Greco Maria Grazia , Bonvino Angelica
Published: June 2005

We report a distinct syndrome of eyelid ptosis, convergent strabismus, abdominal muscle defect, hip dislocation, cryptorchidism and developmental delay in two brothers. Consanguinity in their parents suggests autosomal recessive inheritance.
Brachyolmia: Radiographic and genetic evidence of heterogeneity
Authors: Shohat M. , Lachman R. , Gruber H. E. , Rimoin D. L.
Published: June 2005

Brachyolmia refers to a form of skeletal dysplasia characterized by general platyspondyly without significant epiphyseal, metaphyseal, or diaphyseal changes in the long bones. As a result of a study of 11 patients from 7 different families and a review of the literature we propose that there are 3 and possibly 4 different types of brachyolmia:

Hobaek type—an autosomal recessive condition with universal platyspondyly, irregular, and reduced intervertebral spaces and marked extension of the lateral margins of the vertebrae. Rectangular and elongated vertebral bodies are seen on lateral views of the spine, which become more pronounced with age.

Toledo type—radiographically similar to Hobaek type but also associated with corneal opacities and precocious ossification of costal cartilage. It is uncertain as to whether this represents variability or heterogeneity.

Maroteaux type—an autosomal recessive disorder that is distinguished from Hobaek type by rounding of the anterior and posterior vertebral borders with less elongation on lateral view and less lateral extension on A.P. view. This type may be associated with precocious calcification of the falx cerebri, and minor facial anomalies.

Dominant type—a previously underscribed form which we have observed in a mother and her son. This type has the most severe vertebral changes with flattening and irregularities of the cervical spine.

These clinical, radiological, and genetic differences suggest genetic heterogeneity in this group of platyspondylic disorders.
Osteodysplastic primordial dwarfism: Report of a further case with manifestations similar to those of types I and III
Authors: Haan E. A. , Furness M. E. , Knowles S. , Morris L. L. , Scott G. , Svigos J. M. , Vigneswaren R.
Published: June 2005

We describe a male infant with microcephalic osteodysplastic primordial dwarfism. The clinical and radiological manifestations most closely resemble those of the patient described by Winter et al. to have manifestations overlapping with both osteodysplastic primordial dwarfism types I and III. The classification of the patient within the spectrum of osteodysplastic primordial dwarfism is discussed and the distinctive neuropathology documented.
In utero thrombosis and neonatal gangrene in an infant of a diabetic mother
Authors: Van Allen Margot I. , Jackson J. Craig , Knopp Robert H. , Cone Richard
Published: June 2005

We report an infant of a diabetic mother (IDM) with in utero brachial artery thrombosis and neonatal gangrene to illustrate that there may be an increased risk for arterial as well as venous thrombosis in IDMs. The diagnosis of brachial artery thrombosis was made by using Doppler sonography flow studies and was confirmed with autopsy. The postnatal period was complicated by aortic and mesenteric artery thrombosis, with subsequent necrotizing enterocolitis, renal infarction, and death. Gangrene of a limb presenting at birth is rare, with 32 individuals reported in the literature, including this patient. Twenty‐two percent (7/32) of the infants with peripartum limb gangrene were IDMs. This implies a marked increase in arterial thrombosis in IDMs over the general population. Changes in coagulation factors have been reported in newborn IDMs with poor control of maternal diabetes. Increased clotting and decreased fibrinolysis found in diabetics may lead to arterial thrombosis in IDMs in utero and postnatally. Use of anticoagulants in at‐risk infants should be considered to prevent further thrombosis postnatally. Additionally, IDMs may be at increased risk for thrombotic complications from umbilical artery catheter. In utero thrombosis of the brachial artery may be one mechanism which leads to limb reduction defects in IDMs.
Distal infantile spinal muscular atrophy associated with paralysis of the diaphragm: A variant of infantile spinal muscular atrophy
Authors: Bertini E. , Gadisseux J. L. , Palmieri G. , Ricci E. , Capua M. Di , Ferriere G. , Lyon G.
Published: June 2005

We report the clinical, electrophysiological, and morphological observations of five infants with an unusual form of spinal muscular atrophy (SMA). In these infants muscular weakness and atrophy were initially restricted to the distal limbs and this pattern was associated with paralysis of the diaphragm. The difference between the clinical manifestations of this syndrome and the classical form of infantile spinal muscular atrophy (SMA type 1) as well as other congenital hereditary neuropathies is discussed.
Epiphyseal dysplasia with coxa vara, microcephaly, and normal intelligence in sibs: Expanded spectrum of Lowry‐Wood syndrome?
Authors: Hankenson Lori G. , Ozonoff Maer B. , Cassidy Suzanne B.
Published: June 2005

We report on a brother and sister with epiphyseal dysplasia and coxa vara, microcephaly, and short stature. This constellation of findings is similar to that found in the Lowry‐Wood syndrome (Epiphyseal dysplasia, microcephaly, short stature, and mental retardation). In the sibs we describe, mental retardation is not apparent, and they have the additional finding of developmental coxa vara. Despite these 2 exceptions, this family probably represents the same disorder described by Lowry and Wood (Clinical Genetics 8:269–274,1975), and serves to expand the spectrum of the syndrome to include coxa vara. It is also possible that these sibs represent a previously undescribed syndrome, most likely with autosomal recessive inheritance.
RAPADILINO syndrome with radial and patellar aplasia/hypoplasia as main manifestations
Authors: Kääriäinen Helena , Ryöppy Soini , Norio Reijo
Published: June 2005

A new malformation syndrome is described in a pair of sibs and 3 sporadic patients. The characteristic manifestations are radial aplasia or hypoplasia, absence of thumbs, absent or hypoplastic patellae, dislocations of joints, unusual face, cleft or highly arched palate, diarrhea in infancy, small stature, and normal intelligence. Recessive inheritance seems the most plausible cause. The acronym RAPADILINO syndrome is proposed.
Lymphatic abnormalities in fetuses with posterior cervical cystic hygroma
Authors: Chitayat David , Kalousek Dagmar K. , Bamforth J. Stephen
Published: June 2005

We studied the structure and number of lymph vessels in 12 spontaneously aborted previable fetuses with posterior cervical cystic hygroma and generalized edema of variable origin (monosomy X, trisomy 21, trisomy 13, suspected Noonan syndrome, and lethal multiple pterygium syndrome) and compared them to 5 therapeutically aborted, apparently normal fetuses.

We found that in the non‐45,X fetuses with cystic hygroma and edema the lymphatic vessels at all studied sites were dilated and appeared increased in number. The 4 5 3 fetuses had no recognizable lymphatic vessels in the edematous cutaneous tissue of the limbs, and only occasional dilated vessels in the wall of the nuchal cystic hygroma and in the lungs. These findings may be useful in differentiating between monosomy X and other conditions causing nuchal cystic hygroma in specimens in which the fetus was incomplete andlor cytogenetic study could not be done.
Autosomal dominant microcephaly with mental retardation
Authors: Bawle E. , Horton M.
Published: June 2005

A 3‐year‐old girl, her mother, and maternal uncle had microcephaly and mental retardation. Their facial appearance is characterized by deep‐set eyes, short philtrums, and a “beaked” nose. The mother and uncle live in an adult foster care facility because of mental retardation. The 3‐year‐old girl has a developmental quotient of 55. Mother has normal phenylalanine level and the child's chromosomes are normal. This appears to be a first report of a autosomal dominant form of microcephaly associated with mild to moderate mental retardation in contrast to absent or mild mental retardation described in earlier reports.
Cystic renal disease and cardiovascular anomalies
Authors: Evans Jane A. , Stranc Leonie C.
Published: June 2005

Renal cysts are a relatively common but heterogeneous group of disorders that are increasingly being diagnosed prenatally. Prognosis depends on the type of cystic disease, extent of involvement, and the presence or absence of other anomalies. Czeizel (American Journal of Medical Genetics [Supplement] 2:17–21,1986) indicated that a cystic kidney‐cardiovascular malformation association exists. To investigate this further a population based study of renal cysts and associated anomalies in Manitoba children born between 1979 and 1983 was carried out.

A total of 46 children with renal cysts were identified from multiple sources (1 per 1,824 total births). The most common types were multicystic dysplasia (1/3,226), cystic dysplasia due to lower urinary tract obstruction (1/ 13,932), and infantile polycystic kidney disease (1/20,973). Other anomalies were seen in 72% of cases and 33% had cardiovascular anomalies. A further 11% had patent ductus arteriosus or single umbilical artery. The incidence of cardiovascular defects excluding patent ductus arteriosus or single umbilical artery was 1/174 in the total birth cohort and our data confirmed a strong association of renal cysts with cardiovascular defects in children with malformations (P < 0.001).

The association of cardiac defects with unilateral multicystic dysplasia is especially important. Of the 14 children ascertained with unilateral dysplasia, 4 (28%) had major cardiac defects leading to early death in all instances. Only one of the 4 had additional defects. Unilateral multicystic dysplasia with a normal contralateral kidney usually has a good prognosis. However, recognition of this association with major cardiac defects should alert clinical geneticists to the need for careful assessment of the fetal heart and other systems before counselling high expectations for an optimistic outcome when such cases are diagnosed prenatally.
Lissencephaly, abnormal lymph nodes, and T‐cell deficiency in one patient
Authors: Krawinkel M. B. , Ernst M. , Feller A. , Flad H. D. , Mueller‐Hermelink H. K. , Ulmer A. J. , Schaub J.
Published: June 2005

We report on a child with lissencephaly type I, abnormal lymph nodes, and immunodeficiency, associated with recurrent infections, autoimmune disease, spastic tetraplegia, and psychomotor retardation. Diagnostic measures included cranial computer tomography (CT) and magnetic resonance imaging (MRI) scanning, several in vivo and in vitro immunological tests, and histology of skin, lymph nodes, and liver including electron microscopy and immunohistology. Despite medical supervision, the child died at age 4 years.

A common pathogenetic mechanism of defective migration of neurons and the dysmaturation of lymph nodes is most probable. The T‐cell deficiency may represent a common defect of the development of both neuronal and lymphatic tissue, as the six‐layered cerebral cortex and the B‐cell areas in lymph nodes develop at about the same gestational age. A common defect could also be assumed involving genetically determined cell surface proteins.
Cardio‐facio‐cutaneous (CFC) syndrome: Report of a new patient
Authors: Chrzanowska Kristina , Fryns Jean‐Pierre , Van den Berghe Herman
Published: June 2005

We describe a girl with the cardio‐facio‐cutaneous (CFC) syndrome. She presented most of the characteristics of the new multiple congenital anomalies/mental retardation (MCA/MR) syndrome: unusual facial appearance and ectodermal symptoms, that is, abnormal hair and skin, ventricular septum defect, relative macrocephaly with large ventricles and cortical “atrophy,” submucous cleft palate, and umbilical hernia. Her twin brother died shortly after birth and may have had the same malformation syndrome.
A new autosomal recessive disorder resembling Weaver syndrome
Authors: Teebi Ahmad S. , Sundareshan T. S. , Hammouri Mousa Y. , Al‐Awadi Sadika A. , Al‐Saleh Qasem A.
Published: June 2005

Most reported cases of Weaver syndrome are sporadic, and the mode of inheritance is still unclear. We describe two (male and female) sibs born to consanguineous Bedouin parents with manifestations resembling Weaver syndrome. Both sibs had accelerated growth of prenatal onset, hypotonia, psychomotor retardation, excess loose skin, peculiar craniofacial and acral anomalies, dental dysplasia and/or serrated gums, joint laxity, and hoarse low‐pitched cry. One of them had an accelerated harmonic skeletal maturation. Differentiating features from Weaver syndrome are discussed, and autosomal recessive inheritance is suggested.
Microdeletion in the X‐chromosome and prenatal diagnosis in a family with Norrie disease
Authors: Zhu Danping , Antonarakis Stylianos E. , Schmeckpeper Barbara J. , Diergaarde Paul J. , Greb Anne E. , Maumenee Irene H.
Published: June 2005

We have studied a three‐generation family in which Norrie disease is segregating and have performed prenatal diagnosis on the fetus of an obligatory carrier. Deletions at loci DXS7 and DXS77 defined by probes L1.28, L1.28‐p59, and pX59 were detected in the affected male. DNA studies of chorionic villus biopsy material indicated that the male fetus had inherited the normal allele from the carrier mother. This prediction was confirmed on eye examination at age 5 months.
Case of lethal multiple pterygium syndrome with special reference to the origin of pterygia
Authors: Hartwig N. G. , Vermeij‐Keers Chr. , Bruijn J. A. , van Groningen K. , Ottervanger H. P. , Holm J. P.
Published: June 2005

A case of lethal multiple pterygium syndrome is presented. Besides the anomalies usually associated with this syndrome, cardiac hypertrophy and connective tissue abnormalities were observed. On the basis of these observations, we suggest that an abnormally fragile collagen constitution is the principal disorder in the lethal multiple pterygium syndrome, which is responsible for the pathogenesis of fetal immobility, pterygia, and many of the associated anomalies.
Defective lysosomal release of vitamin B12 (cblF): A hereditary cobalamin metabolic disorder associated with sudden death
Authors: Shih Vivian E. , Axel Sarah M. , Tewksbury John C. , Watkins David , Cooper B. A. , Rosenblatt David S.
Published: June 2005

Here we report on a girl who presented with failure to thrive, developmental delay, minor facial anomalies, stomatitis, skin rashes, macrocytosis, mild homocystinemia‐(uria), and methylmalonic acidemia(uria). Fibroblast studies showed abnormal intracellular cobalamin (vitamin B12) metabolism. Reduced incorporation of 14C from [14C] propionate and [14C] methyltetrahydrofolate into TCA‐precipitable macromolecules reflected decreased synthesis of adenosylcobalamin and methylcobalamin respectively. The diagnosis of cblF mutation was established by demonstrating the accumulation of unmetabolized free cyanocobalamin in fibroblasts and by lack of genetic complementation with fibroblasts from the only other known cblF patient. The defect is in the lysosomal release of endocytosed cobalamin. Administration of hydroxocobalamin resulted in clinical and biochemical improvement but sudden death occurred at age 5 months. The absence of brain pathological changes suggests that early treatment may prevent the neurological complications in cobalamin co‐factor deficiency.
Ullrich‐Turner syndrome in an XY female fetus with deletion of the sex‐determining portion of the Y chromosome
Authors: Blagowidow Natalie , Page David C. , Huff Dale , Mennuti Michael T.
Published: June 2005

Here we describe a fetus in whom a cystic hygroma was detected by ultrasound during the second trimester. Autopsy demonstrated a female fetus with manifestations of Ullrich–Turner syndrome, including gonadal dysgenesis, generalized lymphedema, and preductal aortic coarctation. Surprisingly, the karyotype was 46,XY, with no evidence of mosaicism for a 45,X cell line. Y‐DNA hybridization studies demonstrated a deletion of the sex‐determining segment of the short arm of the Y chromosome. This is the first report, in a fetus, of XY Ullrich‐Turner syndrome due to a Y chromosome deletion.
VACTERL with hydrocephalus: Further delineation of the syndrome(s)
Authors: Evans Jane A. , Stranc Leonie C. , Kaplan Paige , Hunter Alasdair G. W.
Published: June 2005

Central nervous system defects including hydrocephalus are rare in cases of VACTERL association. However, recent reports suggest that there may be one or more disorders in which this combination of anomalies occurs. We report 8 additional patients including a recurrence in a previously described family, review the literature, and provide some population‐based data of VACTERL‐type anomalies in hydrocephalus cases. VACTERL with hydrocephalus appears distinct from hydrolethalus and similar conditions but is itself heterogeneous. The pattern of inheritance of the disorders involved is unclear, but autosomal recessive and sex‐linked forms likely occur. The prognosis of VACTERL cases with hydrocephalus appears much poorer than for those with classic VACTERL anomalies, and the recurrence risk may be higher than for either the VACTERL association or isolated hydrocephalus.
Intermittent thrombocytopenia and absent radii: Report of a patient with additional unusual manifestations
Authors: van Haeringen Arie , Veenstra Foekje , Maaswinkel‐Mooij Petra D. , van de Kamp Jacques J. P.
Published: June 2005

We report on a boy with absent radii and intermittent thrombocytopenia. He has many other manifestations of the thrombocytopenia absent radius (TAR) syndrome but in addition has manifestations not previously described: palatoschisis of the soft palate, subcricoid stenosis, duodenal atresia and extreme sensitivity of chromosomes to X‐rays. Our patient could either represent a unique condition or unusual variability of TAR syndrome.
Hereditary retinal vasculopathy with cerebral white matter lesions
Authors: Gutmann David H. , Fischbeck Kenneth H. , Sergott Robert C.
Published: June 2005

We report on a syndrome of progressive visual loss and leukoencephalopathy affecting several relatives. Affected individuals had evidence of retinal vasculopathy on fluorescein angiogram and periventricular white matter lesions on brain magnetic resonance imaging. The clinical manifestations in this family suggest transmission of an autosomal dominant vasculopathy affecting both retinal and intracranial vessels.
Otocephaly‐midline malformation association
Authors: Hersh Joseph H. , McChane Richard H. , Rosenberg Ellen M. , Powers William H. , Corrigan Cynthia , Pancratz Leslie
Published: June 2005

Otocephaly (“agnathia”) is a developmental field complex with structural defects limited to the craniofacial region. Previously, two infants with otocephaly, situs inversus totalis, renal defects, and vertebral and rib abnormalities were reported by Pauli et al. [Teratology 23:85–93, 1981]. We describe a similarly affected infant male, supporting the existence of this midline malformation association. A generalized disturbance in cell migration from the primitive streak may be its pathogenesis. A search for additional patients among cases of otocephaly may establish its prevalence, patterns of associated anomalies, and cause.
Holoprosencephaly: A developmental field defect
Authors: Johnson Virginia P.
Published: June 2005

Holoprosencephaly refers to a spectrum of craniofacial malformations including cyclopia, ethmocephaly, cebocephaly, and premaxillary agenesis. Etiologic heterogeneity is well documented. Chromosomal, genetic, and teratogenic factors have been implicated. Recognition of holoprosencephaly as a developmental field defect stresses the importance of close scrutiny of relatives for mild forms such as single median incisor, hyptelorism, bifid uvula, of potuitary deficiency.
Prenatal detection of cyclopia associated with interstitial deletion of 2p
Authors: Grundy Howard O. , Niemeyer Pam , Rupani Mahendra K. , Ward Veronica F. , Wassman E. Robert
Published: June 2005

We report on a case of synophthalmic cyclopia and alobar holoprosencephaly associated with an interstitial deletion of the short arm of chromosome 2: del(2)(p21p23). This is the second case with this phenotype in association with deletion in this region, and comparison with the infrequent other cases of 2p deletions suggests a causal relationship between band 2p21 and cyclopia.
Anorectal malformations and Down syndrome
Authors: Zlotogora J. , Abu‐Dalu K. , Lernau O. , Sagi M. , Voss R. , Cohen T.
Published: June 2005

During 1980 to 1986, 89 children with Down syndrome and 42 with imperforate anus were diagnosed among 64,870 liveborn infants in the Jewish population of Jerusalem. Two of the children had both Down syndrome and imperforate anus. This indicates a high incidence of imperforate anus among children with Down syndrome (2.2%).
Expanded phenotype and ethnicity in Setleis syndrome
Authors: Clark Robin Dawn , Golabi Mahin , Lacassie Yves , Hall Bryan , Seto Susan
Published: June 2005

Setleis syndrome, an autosomal recessive disorder characterized by “coarse” face, temporal cutis aplasia, double upper eyelashes, absent lower eyelashes, chronic conjunctivitis, and prominent thick lips, was reported previously in 8 Puerto Rican children. We report on 3 unrelated children (one mentally retarded) with Setleis syndrome who are not of Puerto Rican descent. Two of our patients had imperforate anus, which has not previously been reported. The evolution of the phenotype over time is illustrated.
Esterase D assay in Brazilian retinoblastoma families
Authors: Costanzi Eugenia , da Silva‐Fernandes Maria E. , D'Almeida Vânia , Erwenne Clélia M.
Published: June 2005

The gene related to retinoblastoma (Rb gene) can be considered a model human tumor supressor gene and was assigned to band 13q14, together with the esterase D (ESD) gene. We studied the ESD activity and phenotype in 40 retinoblastoma patients, 50 unaffected relatives, and 85 nonrelated healthy control individuals. ESD activity from patients is significantly different from that of relatives and control individuals, but there was no significant difference between ESD activity from unaffected relatives and control individuals. Twelve and one‐half percent of patients and 4.2% of unaffected relatives with ESD1 phenotype showed a low ESD level. The results showed the importance of ESD studies in all retinoblastoma patients and their relatives.
Re‐evaluation of new X‐linked syndrome for evidence of CHARGE syndrome or association
Authors: Abruzzo Michael A. , Erickson Robert P.
Published: June 2005

Previously, we reported on a family with a new syndrome of cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. This family has been cited in several reports as an example of familial CHARGE syndrome. We do not think that the patients in this family have the Charge syndrome or association. Therefore, we decided to do a follow‐up study on this family to assess the subsequent development of the patients and to determine if they have the CHARGE syndrome. We conclude that our patients do not have familial CHARGE syndrome.
Hypothesis: Homozygosity in tourette syndrome
Authors: Comings David E. , Comings Brenda G. , Knell Ellen
Published: June 2005

We review evidence suggesting that many individuals with Tourette syndrome (TS) may be homozygous for a “Tourette syndrome” gene. This is based on experience with pedigrees on 1,200 TS families, comparison of the occurrence of tics or associated behaviors such as obsessive‐compulsive behavior, panic attacks, attention deficit hyperactivity disorder, and/or severe alcohol or drug abuse, on both the maternal and paternal side in 170 TS families compared to control families, biochemical studies of blood serotonin and tryptophan levels, and other evidence. These observations suggest the inheritance in TS may be best described as semi‐dominant, semi‐recessive. Some of the implications of this proposal are discussed.
Functional methionine synthase deficiency (cblE and cblG): Clinical and biochemical heterogeneity
Authors: Watkin David , Rosenblatt David S.
Published: June 2005

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5‐methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl‐dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near‐normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.
Prenatal diagnosis of friedreich ataxia
Authors: Wallis J. , Shaw J. , Wilkes D. , Farrall M. , Williamson R. , Chamberlain S. , Skare J. C. , Milunsky A.
Published: June 2005

Friedreich ataxia is a progressive neurodegenerative disorder affecting the peripheral and central nervous systems. One in 50,000 of the population are affected by this recessively inherited disorder, with onset usually before puberty. The recent localization of the disease locus to chromosome 9 has made it possible to provide genetic counselling to families with at least one affected child. Tight linkage of the disease mutation to an anonymous DNA marker MCT112 (D9S15) has been shown with a pairwise lod score of 36.1 at 0=0. We report here the first prenatal diagnosis in Friedreich ataxia. Using MCT112 and the confidence interval approach, we have calculated risks for a fully informative family with one affected sib.
Börjeson‐Forssman‐Lehmann syndrome: Clinical manifestations and gene localization to Xq26‐27
Authors: Turner Gillian , Gedeon Agi , Mulley John , Sutherland Grant , Rae John , Power Keith , Arthur Ian
Published: June 2005

We have studied 7 males in one family with mild/moderate intellectual handicap, long thick ears, deep‐set eyes, small testes, and post pubertal gynecomastia. The affected males and some of the heterozygous females also had tapering fingers and short, widely spaced flexed toes. The pedigree demonstrates X‐linked recessive inheritance. The clinical manifestations are similar to those described in the Börjeson‐Forssman‐Lehmann (BFL) syndrome but differ in the degree of mental handicap and the absence of “dwarfism” and microcephaly. This milder manifestation may represent either phenotypic or genotypic variation. DNA marker studies demonstrated linkage to theDXS86,DXS51, andF9 cluster at Xq26‐q27. The maximum lod score was 2.1 withDXS51, at θ = 0.0. Definite recombinants were observed betweenDXS10(at Xq26 but proximal toDXS86),DXS105(at Xq27 but distal toF9), andBFL. Thus, the regional localization forBFLis Xq26‐q27 betweenDXS10andDXS105.
Trisomy 22: No longer an enigma
Authors: Kukolich Mary K. , Kulharya Anita , Jalal S. M. , Drummond‐Borg Margaret
Published: June 2005

We describe a live‐born male with 47,XY, + 22. He had multiple congenital anomalies, severe growth retardation and psychomotor delay. Physical manifestations included broad nasal bridge, epicanthic folds, micrognathia, long philtrum, cleft palate, microcephaly with prominent occiput, apparently low‐set malformed ears, heart murmur, genital anomaly, clinodactyly of the fifth fingers, and a low total finger ridge count. He died just before his 3rd birthday. Chromosome analysis by multiple banding techniques based on lymphocyte and fibroblast cultures confirm that the boy had complete trisomy 22.
Familial hypoplastic glomerulocystic kidney disease: A definite entity with dominant inheritance
Authors: Kaplan Bernard S. , Gordon Isky , Pincott John , Barratt T. Martin
Published: June 2005

Autosomal dominant (or possibly X‐linked) inheritance of familial hypoplastic glomerulocystic kidneys is described in a mother and son who both had stable, chronic renal failure, cystic kidneys by ultrasound examination, glomerular cysts as demonstrated histologically, and malformed renal calyces. There was no evidence of other congenital abnormalities apart from prognathism, small stature and pyloric stenosis. Hepatic fibrosis was not evident in a liver biopsy specimen. These findings add further confirmation to the existence of the syndrome of familial hypoplastic glomerulocystic kidney disease with dominant inheritance.
Type II collagen screening in the human chondrodysplasias
Authors: Horton William A. , Campbell Dianna , Machado Mirta A. , Chou Jean
Published: June 2005

Abnormalities of type II collagen have been considered strong candidates for causing human chondrody splasias. We have employed peptide mapping to screen for several types of type II collagen abnormalities in cartilage samples from 66 patients with 20 separate disorders. Except for achondrogenesis type II (Langer‐Saldino) and spondyloepiphyseal dysplasia (SED) congenita in which abnormalities have been described and diastrophic dysplasia in which the changes were probably secondary, no abnormalities were detected. Within the limitations of the screening technique, the results combined with other data from the literature suggest that abnormalities of this molecule are not common causes of chondrody splasias outside of the achondrogenesis type II‐SED congenita family of disorders.
Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation
Authors: Hennekam R. C. M. , Geerdink R. A. , Hamel B. C. J. , Hennekam F. A. M. , Kraus P. , Rammeloo J. A. , Tillemans A. A. W.
Published: June 2005

We report on two male and two female relatives with intestinal lymphangiectasia; severe lymphedema of limbs, genitalia, and face; facial anomalies; seizures; mild growth retardation; and moderate mental retardation. Main facial anomalies are a flat face, flat nasal bridge, hypertelorism, small mouth, tooth anomalies, and ear defects. Their parents are consanguineous. This disorder probably is an hitherto undescribed autosomal recessive syndrome.
Dermatoglyphic analysis of autistic Basque children
Authors: Arrieta M. I. , Martinez B. , Criado B. , Simón A. , Salazar L. , Lostao C. M.
Published: June 2005

We have analyzed the digital and palmar dermatoglyphics in a sample of autistic children from the Basque Country. The results have been compared with those from a control sample having the same characteristics relative to the ethnic region. We found significant differences between the digital dermatoglyphics of autistic boys and control boys. Autistic children have a higher frequency of transitional radial loops and a lower frequency of dicentric whorls; also the total finger ridge count (TFRC) and radial count are lower in autistic individuals. There were no significant differences in the girls. In palmar dermatoglyphics, autistic girls have a lower frequency of radial loops in the hypothenar area, and the value of the “atd” angle is higher than in control girls. These differences were significant. The a‐b interdigital ridge count is significantly lower in autistic boys. Autistic children of both sexes have a higher frequency of aberrant palmar creases. The results obtained in the present study do not contradict the hypothesis that genetic factors may be important in autism of unknown cause.