bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucolipidosis type IV: Clinical manifestations and natural history
Authors: Chitayat David , Meunier Catherine M. , Hodgkinson Kathy A. , Silver Kenneth , Flanders Michael , Anderson Ilse J. , Little John M. , Whiteman David A. H. , Carpenter Stirling
Published: June 2005

The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi‐Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.
Familial congenital brachial palsy
Authors: Mollica F. , Volti S. Li , Grasso A. , De Simone D.
Published: June 2005

Eight relatives in a Sicilian family, including a sibship of 5, were affected with severe unilateral congenital brachial palsy (CBP) in a pattern suggesting autosomal dominant inheritance with reduced penetrance (6 cases affected on the right, 2 on the left). X‐linked inheritance with expression in heterozygous females cannot be excluded.
Early childhood diagnosis of acoustic neuromas in presymptomatic individuals at risk for neurofibromatosis 2
Authors: Pastores Gregory M. , Michels Virginia V. , Jack Clifford R.
Published: June 2005

We report on a family in which individuals at risk for NF 2 were investigated with the use of gadolinium‐enhanced MRI. This technique has allowed the diagnosis of small ( < 8 mm) acoustic neuromas in two asymptomatic children (age 7 and 11), one of whom had normal audiometric and brainstem‐evoked response testing. To our knowledge these are the youngest asymptomatic patients in whom the diagnosis of NF 2 has been demonstrated. It is possible that acoustic neuromas develop at an early age more commonly than recognized previously.

The early diagnosis of acoustic neuromas with the use of gadolinium‐enhanced MRI may lead to better outcome following surgery. This technique will provide the opportunity to better determine the natural course of this disease.
Problems in ascertainment of transmitting males in Martin‐Bell syndrome
Authors: Loesch Danuta Z. , Hay David A. , Leversha Margaret
Published: June 2005

The difficulty of assigning families affected with the Martin‐Bell syndrome (MBS) into the category of male transmission is emphasised and illustrated by examples of 3 MBS families. These examples demonstrate how the ability to detect transmitting males depends on the number of generations available for investigation, and also on the “spread” of clinical investigation across many branches of the family regardless of what appears to be an unremarkable family history. Some unusual properties of male transmission are shown, and the problem of selective ascertainment of the particular MBS male individuals in different generations in a set of pedigrees is discussed.
Generalized chondrodysplasia punctata with shortness of humeri and brachymetacarpy: Humero‐metacarpal (HM) type: Variation or heterogeneity?
Authors: Borochowitz Zvi
Published: June 2005

We report on a girl with symmetrical rhizomelic shortness of the upper limbs and punctate epiphyseal calcifications noted at birth. Presumably she has normal height, but short nose, short hands, and normal mentation; and on roentgenograms short and wide humeri, symmetrical brachymetacarpy, especially of the 4th metacarpals, and hypoplastic distal phalanges, sagittal clefting of vertebral bodies, and punctate calcifications at various areas including the entire spine, sacrum, hands, feet, trachea, and thyroid cartilage. It is an apparently new syndrome of chondrodysplasia punctata (CP), quite distinct from the classic from (Conradi‐Hünerman type), as well as the other well‐defined forms of CP. We thus suggest the term chondrodysplasia punctata, humero‐metacarpal (HM) type.
De novo duplication of 17p [dup(17)(p12→p11.2)]: Report of an additional case with confirmation of the cytogenetic, phenotypic, and developmental aspects
Authors: Kozma Chahira , Meck Jeanne M. , Loomis Karen J. , Galindo Hugo C.
Published: June 2005

We describe an apparent de novo duplication of bands 17p11.2 and p12. A comparison of the manifestations of a previously reported case with a similar karyotype [Magenis et al., Am J Med Genet 24:415‐420 (1986)] and of our own case seems to indicate a characteristic pattern which includes prenatal and postnatal growth retardation, facial changes, club feet, and mild developmental deficits. The prominent facial changes are a relatively triangular face, downslanted palpebral fissures, malocclusion, and abnormal ears. In addition, this condition appears to be milder than other duplications of the short arm of chromosome 17, namely trisomy 17p and dup(17)(p11.2→cen).
Molecular analysis of gaucher disease: Screening of patients in the Montreal/Quebec region
Authors: Choy Francis Y. M. , Woo Mary , Der Kaloustian Vazken M.
Published: June 2005

Gaucher disease, the most prevalent lysosomal storage disease, is an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. Genomic DNA of the structural gene of glucocerebrosidase from normal individuals and fifteen unrelated patients with the three clinical forms of Gaucher disease from the Montreal/Quebec region were amplified by the polymerase chain reaction technique. Allele‐specific oli‐gonucleotide dot blot hybridization and restriction fragment length polymorphism were used to screen for five of the mutations [mutations 120, 370, 415, 444 (Nci), and 463] in exons 5,9, and 10 of glucocerebrosidase gene. It was noted that all of the patients had at least one of the known mutant alleles. However, 9 patients (9/15 = 60%) had an unknown allele. Mutation 370 in exon 9 was present in the heteroallelic form in eight out of the nine patients with type 1 Gaucher disease, but was present in none of the six patients with type 2 or type 3 Gaucher disease. The Nci mutation in exon 10 was present in the heteroallelic form in three patients with type 1 Gaucher disease and in either the heteroallelic or homoallelic form in all of the six patients with type 2 or type 3 Gaucher disease. The 415/Nci mutations were found in a mildly affected 29‐year‐old patient with type 1 Gaucher disease, as well as in an infant with the type 2 form. These findings demonstrate the clinical and molecular genetic heterogeneities of Gaucher disease, the presence of unknown Gaucher allele(s) in most (60%) of the patients surveyed, and the occasional inexplicable lack of phenotype‐genotype correlation among some patients. It also suggests that other genetic factor(s) may be implicated in determining the phenotypic expression of Gaucher disease.
Campomelia, polycystic dysplasia, and cervical lymphocele in two sibs
Authors: Urioste Miguel , Arroyo Antonio , Martínez‐Frías María‐Luisa
Published: June 2005

We report on 2 sibs with a similar MCA pattern consisting of generalized lymphedema, cervical lymphocele, shortness of limbs, bowed long bones, and multicystic kidneys with fibrotic liver or pancreas. To our knowledge, this is the second observation of such a combination of defects in sibs, and it confirms the existence of the syndrome reported by Cumming et al. [1986] and its autosomal recessive inheritance.
Hallermann‐Streiff syndrome with hypopituitarism contributing to growth failure
Authors: Pivnick Enikö K. , Burstein Stephen , Sid Wilroy R. , Kaufman Robert A. , Ward Jewell C.
Published: June 2005

A 35‐month‐old black boy with Hallermann–Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be some what altered due to his racial background. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.
Respiratory obstruction and cor pulmonale in the Hallermann‐Streiff syndrome
Authors: Robinow Meinhard
Published: June 2005

The risk of respiratory death in the Hallermann‐Streiff syndrome is not insignificant, particularly in the neonatal period and in infancy. Upper airway obstruction may result from small nares and glossoptosis secondary to micrognathia, which sometimes lead to cor pulmonale. I report on a patient with such problems.
Genetic analysis of cleft lip with or without cleft palate in Madras, India
Authors: Nemana Lakshmi J. , Marazita Mary L. , Melnick Michael
Published: June 2005

We performed a genetic analysis of 331 nonsyndromic cleft lip with or without cleft palate (CL ± P) proband families ascertained in Madras, India. Predictions of the multifactorial threshold (MF/T) model are tested; goodness‐of‐fit tests of the MF/T model and complex segregation analysis are also utilized to clarify the genetic etiology of CL ± P in this study population. There was little evidence for the MF/T model. The most reasonable conclusion from mixed model analysis is that of a major locus with reduced transmission probability. This is not altogether surprising if manifestation of CL ± P also depends on in utero exposure to harmful environmental agents during the critical period of facial development, as suggested by Melnick et al. [1980] and demonstrated in an animal model of CL ± P [Melnick et al., 1981]. Further the results in the Madras population are quite similar to those in other populations of Europe and Asia.
Ectopia lentis and aortic root dilatation in congenital contractural arachnodactyly
Authors: Bawle Erawati , Quigg Mary Helen
Published: June 2005

Congenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis, and a distinct “crumpled ear” deformity. While the disorder is similar to Marfan syndrome, it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echo‐cardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients.
Congenital hypothalamic hamartoma syndrome: Nosological discussion and minimum diagnostic criteria of a possibly familial form
Authors: Encha‐Razavi F. , Larroche J. C. , Roume J. , Migne G. , Delezoide Al. , Gonzales M. , Mulliez N.
Published: June 2005

We report on congenital hypothalamic hamartomas, discovered at autopsy in 3 unrelated fetuses. In the first 2 patients, the tumor was associated with skeletal dysplasia only. In the third patient, it was part of a non‐random congenital malformation association, suggestive of Meckel syndrome. In one family, a previous boy died soon after birth with similar craniofacial and skeletal abnormalities.

As far as we know, the association between isolated skeletal dysplasia and congenital hypothalamic hamartomas has not yet been documented in the literature. Nevertheless, a spectrum of skeletal abnormalities has been described in association with congenital hypothalamic “hamartoblastoma” and a constellation of variable visceral malformations under the eponym of “Pallister‐Hall syndrome” (PHS).

A detailed analysis of the PHS reported cases shows that only skeletal dysplasia and oro‐facial abnormalities are present constantly. They show similarities with those found in our first 2 cases.

These findings prompt us to consider skeletal dysplasia and oro‐facial abnormalities as common denominator and minimum criteria required to define a nosologically distinct, possibly familial entity, which we suggest calling “congenital hypothalamic hamartoma syndrome” (CHHS).
Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes
Authors: Collins Felicity A. , Murphy Dennis L. , Reiss Allan L. , Sims Katherine B. , Lewis John G. , Freund Lisa , Karoum Farouk , Zhu Danping , Maumenee Irene H. , Antonarakis Stylianos E.
Published: June 2005

Norrie disease is a rare X‐linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy‐habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for “chronic hypomania and schizotypal features.” The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus.
Low level mosaicism for a balanced 7;14 translocation in the father of an abnormal 7q + child
Authors: Sciorra Leonard J. , Schlenker Ellen , Toke David , Brady‐Yasbin Sheila , Day‐Salvatore Debra , Lee Ming‐Liang
Published: June 2005

A child with a 7q + chromosome abnormality had a father with 0.5% mosaicism for a balanced 7;14 translocation. This mosaicism was not found in 100 fibroblasts. This degree of mosaicism is well below the limits usually detected by standard clinical cytogenetic protocols. However, the one abnormal cell cannot be disregarded in this case, since it can serve as an explanation of the child's genotype. This case serves to illustrate the need for detecting subtle degrees of mosaicism for structural anomalies in humans and brings to question the true population frequencies of mosaic balanced translocation carriers.
Autosomal dominant erythromelalgia
Authors: Finley W. H. , Lindsey J. R. , Fine J.‐D. , Dixon G. A. , Burbank M. K.
Published: June 2005

We present a kindred of 29 persons affected with erythromelalgia (erythermalgia) in 5 generations. This paper updates the family reported by Burbank et al. [1966]. Patients have symptoms of intermittent intense burning limb pain related to increased skin temperature. No successful treatment has been identified, and the pathogenetic mechanism has not been established. Most affected individuals are female.
DNA mutation analysis of Gaucher patients
Authors: Sidransky Ellen , Tsuji Shoji , Martin Brian M. , Stubblefield Barbara , Ginns Edward I.
Published: June 2005

We evaluated 62 Gaucher patients to determine whether patients with similar phenotypes had the same DNA point mutations. Genomic DNA from these Gaucher patients was screened for the 3 most frequent single‐point mutations, occurring in 69% of the 124 patient alleles, and resulting in changes in amino acids 370, 444, and 463. Many different genotypes were observed, at least one of which is present in all 3 types of Gaucher disease. No specific symptom complex could be correlated with a unique genotype. Even the more clinically homogeneous subgroups of Gaucher patients contained several genotypes. This study further emphasizes the need for caution in making clinical predictions on the basis of current genotype analysis, especially since one might not discern a fetus affected with type 2 disease by current DNA studies. The severity of involvement in type 1 disease could also not be predicted. Thus, even limiting our focus to 3 isolated common point mutations, a given genotype cannot be uniquely correlated with a specific prognosis.
Variability of Stickler syndrome
Authors: Zlotogora J. , Sagi M. , Schuper A. , Leiba H. , Merin S.
Published: June 2005

Stickler syndrome is a dominantly inherited disorder characterized by ocular and nonocular manifestations. The phenotype of the affected patients is known to be variable. Our study of 3 families and a review of the literature show that the variability is mostly interfamilial while in each family less variability is present. In one family all the patients had high myopia and most developed a retinal detachment at a young age. In the second family the major symptoms were cleft palate and characteristic facial changes in presence of mild ocular changes. In the third family, all patients had a marfanoid habitus, high myopia, and mental retardation.

Interfamilial variability coupled with intrafamilial similarities in clinical manifestation may indicate that the so‐called Stickler syndrome represents in fact a phenotype and not a single genetic entity.
Canine X‐linked muscular dystrophy as an animal model of Duchenne muscular dystrophy: A review
Authors: Valentine Beth A. , Winand Nena J. , Pradhan Deepti , Moise N. Sydney , de Lahunta Alexander , Kornegay Joe N. , Cooper Barry J.
Published: June 2005

Canine X‐linked muscular dystrophy is a spontaneously occurring, progressive, degenerative myopathy of dogs that is clinically and pathologically similar to Duchenne muscular dystrophy in man. The molecular basis for the disease has been shown to be a lack of dystrophin, the protein product of the Duchenne muscular dystrophy gene. Breeding colonies of dystrophic dogs have been established. This report reviews the findings of genetic, clinical, pathologic, molecular biologic, and immunocytochemical studies of the canine model, and compares the features of the canine disease to those of Duchenne dystrophy in man.
Growth hormone deficiency and empty sella syndrome in a boy with dup(x)(q13.3→q21.2)
Authors: Yokoyama Yuji , Narahara Kouji , Tsuji Kazushiro , Moriwake Tadashi , Kanzaki Susumu , Murakami Masae , Namba Hiroshi , Ninomiya Shinsuke , Higuchi Joji , Seino Yoshiki
Published: June 2005

A 28/12‐year‐old boy with severe growth failure and mental retardation was found to have a maternally derived tandem duplication of the long arm of X chromosome, dup(X) (q13.3→q21.2). Karyotypic interpretation was further confirmed in this patient by a double gene dose for red blood cell phosphoglycerate kinase. DNA replication study showed that the duplicated X chromosome was always late replicating in peripheral blood lymphocytes as well as in skin fibroblasts from the mother. Endocrine studies in the patient demonstrated growth hormone deficiency. Magnetic resonance imaging of the head then disclosed the empty sella syndrome. This appears to be the first report of a dup(Xq) patient associated with a growth hormone deficiency and the empty sella syndrome. We emphasize that duplication of the proximal Xq in males represents another microduplication syndrome (Thode‐Leonard syndrome).
Short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot: A new autosomal recessive syndrome
Authors: Richieri‐Costa A. , Pereira Sonia Cristina Silveira
Published: June 2005

We report on 5 unrelated Brazilian children with short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot. Genetic aspects and phenotypic manifestations are compared with those of previous reports of acrofacial dysostoses and with other Robin sequence syndromes. We suspect that these patients present a previously undescribed autosomal recessive syndrome.
Two distinct mutations in a single dystrophin gene: Chance occurrence or premutation?
Authors: Laing N. G. , Layton M. G. , Johnsen R. D. , Chandler D. C. , Mears M. E. , Goldblatt J. , Kakulas B. A.
Published: June 2005

We report on a kindred segregating 2 distinct mutations of a dystrophin gene. DNA analysis showed that the second mutation, a deletion, arose in the same gene carrying the primary defect which produced a Becker phenotype in the affected males. The DNA data for this family are reported and the alternative explanations of chance occurrence and premutation are discussed to explain these unusual findings.
New skeletal dysplasia with unique brachydactyly
Authors: Mononen Tarja K. , Karnes Pamela S. , Senac Melvin O. , Falk Rena E.
Published: June 2005

We report on 2 male propositi, their mothers, and a maternal aunt with a new skeletal dysplasia associated with a unique pattern of digital malformation, variable mild short stature, and mild bowleg with proximal overgrowth of the fibula. The digital malformations comprise a pattern of brachydactyly which includes short, abducted thumbs, short index fingers, and markedly short, abducted great toes. The radiographic findings include hypoplastic thumbs and great toes with short first metacarpals and first metatarsals, absent distal phalanges of the index fingers and second toes, and coalescence of the carpal and tarsal bones. Radiographs of the long bones show mild metaphyseal and epiphyseal irregularity, tibial spurs, and relative elongation of the fibulae. The males are very similarly affected whereas the females show phenotypic variation and are generally less severely affected. The family histories from 2 fairly extensive pedigrees suggest X‐linked dominant inheritance.
Case of multivertebral anomalies, cloacal dysgenesis, and other anomalies presenting prenatally as cystic kidneys
Authors: Murr Michel M. , Waziri Mary H. , Schelper Robert L. , Abu‐Youself Monzer
Published: June 2005

We describe a newborn boy on whom prenatal ultrasonography demonstrated intrauterine growth retardation, multiple vertebral anomalies, cystic kidneys, and oligohydramnios. Autopsy findings included multiple vertebral anomalies, cloacal dysgenesis (imperforate anus, vesicorectal fistula, and bilateral renal dysplasia), sacral absence, single umbilical artery, pulmonary hypoplasia, scoliosis, and hexadactyly of the left thumb. Although our case resembles a previously described case, a definitive diagnosis could not be made. The differential diagnosis included a variant of spondylocostal dysostosis and the VATER association.
Vertebral hypersegmentation in a case of the VATER association
Authors: Wulfsberg Eric A. , Phillips‐Dawkins Terri L. , Thomas Ronald L.
Published: June 2005

Associations are statistical clusterings of malformations not known to be polytopic field defects, sequences, or syndromes. The VATER association is a nonrandom association of malformations including vertebral, anal, cardiovascular, tracheoesophageal, genitourinary, and limb defects. The caudal “dysplasia” sequence of lumbosacral vertebral defects, genitourinary abnormalities, and imperforate anus overlaps the VATER association. The cloacal membrane agenesis sequence is a pattern of malformations resulting in the absence of anal, genital, and urinary orifices with associated malformations in surrounding structures. We report on a 37‐week gestation liveborn male with oligohydramnios deformations, tetralogy of Fallot, “H‐type” tracheoesophageal fistula, duodenal atresia, imperforate anus, urethral atresia, undescended testes, absent right kidney with a small dysplastic left kidney, a “cloacal‐like” abnormality of the bladder and distal bowel, and thoracic and lumbar vertebral hypersegmentation. This patient has manifestations of the VATER association, the caudal dysplasia sequence, and the cloacal membrane agenesis sequence. We propose that some of his defects may represent a malformation sequence secondary to excessive embryonic flexion resulting from vertebral hypersegmentation.
Monozygotic twin girls with congenital malformations resembling Fanconi anemia
Authors: Poole Steven R. , Smith Ann C. M. , Hays Taru , McGavran Loris , Auerbach Arleen D.
Published: June 2005

Monozygotic (MZ) twin girls, diagnosed at birth to have Fanconi anemia (FA) on the basis of multiple anomalies and an apparently increased baseline chromosomal breakage frequency in one twin, have been followed prospectively for 13 years. They have not developed aplastic anemia or other hematologic manifestations of FA. There was no evidence for increased baseline or diepoxybutane (DEB)‐induced chromosomal breakage in either twin when the studies were repeated in Denver as well as in New York. Since the cellular phenotype must be considered in establishing the diagnosis of FA, these MZ twins should not be classified as affected with FA. Using the scoring system for FA diagnosis developed by Auerbach et al. [1989], the probability coefficients of their having FA based solely on clinical findings, prior to DEB testing, were .75 and .92, respectively. When the combination of their anomalies are taken together, their FA probability coefficient is .98. Through the International FA Registry, 15 additional patients have been identified with an FA probability score of .75 or greater, but who have not developed aplastic anemia and who are DEB negative. These patients, as well as the twins described in this report, are most likely a heterogeneous group and may represent other syndromes like Holt‐Oram, VATER, VACTERL and IVIC, with genetic as well as nongenetic etiologies. These cases demonstrate the importance of testing with DEB or other DNA crosslinking agent in order to discriminate between FA and other syndromes with a similar phenotype.
New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians
Authors: Marles Sandra L. , Greenberg Cheryl R. , Persaud Trivedi V. N. , Shuckett E. Paul , Chudley Albert E.
Published: June 2005

We report on 6 (3 male, 3 female) Manitoba Indian children with hypertelorism and variable combinations of unilateral eye malformations, aberrant anterolateral scalp hairline, and nasal and anal anomalies. These children belong to 4 related families. The parents and 7 other sibs are clinically unaffected. The family histories are otherwise unremarkable. The presence of 2 major malformations in sibs and related individuals (with unaffected parents) suggests that this is a newly described pleiotropic autosomal recessive syndrome. The differential diagnosis includes cryptophthalmos syndrome and several other related malformation syndromes. Although multifactorial determination cannot be excluded, the inbred, isolated population and distribution make autosomal recessive inheritance more likely.
Maternal serum α‐fetoprotein screening and fetal chromosome anomalies: Is lowering maternal age for amniocentesis preferable?
Authors: Kaffe Sara , Hsu Lillian Y. F.
Published: June 2005

We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098 patients referred for amniocentesis because of low maternal serum α‐fetoprotein (MSAFP) to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for “maternal anxiety.”

Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age‐related incidence estimates. The frequency of chromosome anomalies in cases studied because of “maternal anxiety” with no prior screening was similar to that in the group referred for low MSAFP (1.38 and 1.27%, respectively). A relatively higher frequency (2.02%) was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. “Lowering” maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.
Is autism associated with the fragile X syndrome?
Authors: Fisch Gene S.
Published: June 2005

In addition to mental retardation (MR), fragile X [fra(X)] has been associated with other developmental disabilities, autism in particular. Recently, several studies have concluded that the association of fra(X) with autism is at best weak and perhaps nonexistent. This study examined reports of previously published data from an epidemiological perspective to determine if the prevalence of fra(X) among autistic males was significantly different from that among MR males. Nineteen studies of autistic males and 21 studies of MR males were analyzed from 59 examined. Of 5601 MR males tested, 307 (5.5%) were cytogenetically positive. Of 1006 autistic males, 54 (5.4%) were positive. Analysis indicated no statistical difference between these proportions (Z=0.014; p>.50). An odds ratio (OR) was also computed to determine the risk of autism from fra(X). Estimated OR≈︁1.0 [0.73, 1.32]. Attributable risk (AR), the proportionate excess risk of autism associated with exposure to fra(X) was AR≈︁0.0. That is, there was no attributable risk of autism from fra(X). The association of fra(X) with autism may reflect the association with MR that generally accompanies autism, as several earlier reports have noted. However, the similarity in prevalence of fra(X) among autistic and MR males may be biased in that studies which find no instances of fra(X) among autistic males represent 12% of the pooled sample.
Abnormal behaviors of young girls with fragile X syndrome
Authors: Lachiewicz Ave M.
Published: June 2005

Mothers of 38 young girls with fragile X [fra(X)] between the ages of 4 and 11 years filled out the Child Behavior Checklist. Forty‐seven percent of the girls had T scores > 70 on the hyperactive and social withdrawal scales. Between 26% and 15% of the girls also had high T scores on the depressed scale, on the schizoid‐obsessive scale (for 6 to 11 year olds), on the schizoid on anxious scale (for 4 and 5 year olds), and on the aggressive scale. Although a high score on a scale of the Child Behavior Checklist does not constitute a medical diagnosis, it can alert clinicians to abnormal behaviors that warrant further assessment. These behaviors may also alert the clinician to the possibility of fra(X) syndrome when they are seen in their patients. The high percentage of girls with fra(X), who seem to have abnormal behaviors, provides good reason to diagnose them in their early years, not just for genetic counseling purposes, but so that they can receive appropriate intervention services.
Problem solving limitations among cytogenetically expressing fragile X women
Authors: Mazzocco Michele M. M. , Hagerman Randi J. , Pennington Bruce F.
Published: June 2005

Neurocognitive deficits among fragile X individuals have been reported for both high and low functioning individuals. Recent findings from our research suggest a specific neurocognitive phenotype among fragile X women that is characterized by deficits on tests of frontal lobe functioning. In this paper, we examine in more detail the performance of 10 cytogenetically expressing women and 10 control women on 2 problem solving measures considered sensitive to frontal lobe functions: the Contingency Naming Test and the Tower of Hanoi. The results pertaining to each test suggest that fragile X women, relative to control women, are less able to solve a problem when the difficulty of the problem is increased by requiring simultaneous consideration of additional information. These findings have important implications for remediation strategies designed for affected fragile X individuals.
Characterization of a highly polymorphic dinucleotide repeat 150 KB proximal to the fragile X site
Authors: Riggins Gregory J. , Sherman Stephanie L. , Oostra Ben A. , Sutcliffe James S. , Feitell David , Nelson David L. , Van Oost Bernard A. , Smits Arie P. T. , Ramos Feliciano J. , Pfendner Ellen , Kuhl Derek P. A. , Caskey C. Thomas , Warren Stephen T.
Published: June 2005

Fragile X [fra (X)] syndrome is a frequently encountered form of mental retardation and is inherited as an X‐linked semi‐dominant trait with reduced penetrance. We report here the characterization of a highly polymorphic dinucleotide repeat, DXS 548, which is approximately 150 kb proximal to the fra(X) site and the associated FMR‐1 gene. DXS 548 is tightly linked to the fra(X) syndrome locus (FRAXA) without recombination (LOD = 9.07 with q of 0) in selected families with crossovers between FRAXA and very closely linked flanking markers. This dinucleotide repeat could be useful in determining the parental origin of a new fra(X) mutations and evaluating the role of FMR‐1 in X‐linked non‐specific mental retardation.
Characterization of new PCR based markers for mapping and diagnosis: AC dinucleotide repeat markers at the DXS237 (GMGX9) and DXS102 (cX38.1) loci
Authors: Gedeon Agi K. , Holman Kathy , Richards Robert I. , Mulley John C.
Published: June 2005

Genomic insert DNAs from 45 probes representing 113.4 kb of the X chromosome were screened for AC dinucleotide repeat sequence. Two new AC repeat sequences were identified with length polymorphism based on variation in repeat copy number. One at DXS237 exhibits 44% heterozygosity and is potentially useful for rapid diagnosis and mapping of X‐linked disorders in Xp22.3. The other, at DXS102 in Xq26, has 71% heterozygosity. This marker will improve accuracy of diagnoses by linkage for families with Börjeson‐Forssman‐Lehmann syndrome. Review of the literature has identified 31 PCR based markers on the X chromosome, with minimum heterozygosity of 50%, applicable to the mapping and diagnosis of X‐linked disorders.
Penetrance of Fra(X) gene: Influence of grandparental origin of the gene, mental status of the carrier mother, and presence of a normal transmitting male
Authors: Smits Arie P. T. , van Oost Bernard A. , de Haan Anton F. J. , Hamel Ben C. J. , Dreesen Jos C. F. M. , Smeets Dominique F. C. M.
Published: June 2005

Previous studies have indicated that the fragile X [fra(X)] gene does not show full penetrance (mental impairment) in carrier females or “carrier” males. The phenomenon of non‐expressing carrier males distinguishes the fra(X) syndrome from all other known X‐linked disorders. Moreover, penetrance of the fra(X) gene apparently does not show random distribution within fra(X) families, but seems to be reduced in sibs of normal transmitting males (NTM's). The availability of many large multigeneration fra(X) families, studied by cytogenetic and DNA analyses, enabled us to refine the estimates of the penetrance. From our data we conclude that the penetrance in daughters of carrier females is determined by the mental status of the mother. In sons of carrier females, the observed penetrance appears to be influenced by the grandparental origin of the gene as well as by the mental status of the mother. However, in contrast with the average penetrance, we observed a strongly reduced penetrance of the fra(X) gene in brothers (14%) and sisters (21%) of NTM's. These findings have profound implications for genetic counseling.
Clasped‐thumb mental retardation (MASA) syndrome: Confirmation of linkage to Xq28
Authors: Macias Vincent R. , Day Donald W. , King Teresa E. , Wilson Golder N.
Published: June 2005

We describe a 5‐generation Hispanic family with 13 males and 1 female affected with MASA syndrome. The proposita, a 17‐year‐old female, and her affected male relatives shared many of the cognate manifestations–mental retardation (14/14), aphasia or delayed speech (13/13), shuffling gait (8/13), adduction of thumbs (14/14)–as well as scoliosis (2/13) and increased deep tendon reflexes in the lower extremities (10/13). Southern analysis with the polymorphic DNA probes DXS14 (Xp11), DXS72 (Xq21), and F8C (Xq28) confirmed linkage to the Xq28 region with a maximum lod score of 3.01 for this family.
New X‐linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum
Authors: Proud Virginia K. , Levine Clive , Carpenter Nancy J.
Published: June 2005

We report on 4 generations in a family with 3 living males, 3 males who died in infancy, and 3 females with neurologic impairment and agenesis of the corpus callosum (ACC). Manifestations in the surviving males include severe acquired micrencephaly, mental retardation, limb contractures, scoliosis, tapered digits with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophris, optic atrophy, broad alveolar ridges and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias. Two affected females were less severely impaired and continued to be socially responsive as adults, but had spastic quadriplegia and seizures. One obligate heterozygote was retarded with emotional problems while another obligate carrier female and her daughter were clinically normal. Pedigree analysis suggested X‐linked inheritance with variable expression in females. These findings are inconsistent with the well‐described X‐linked conditions with ACC including FG syndrome and Aicairdi syndrome. ACC has not been described in Coffin‐Lowry syndrome, a condition with similar clinical findings, which also demonstrates marked variability of expression in carrier females.

In order to assist in carrier determination, brain imaging studies and DNA linkage analysis of the affected relatives was performed. We found a spectrum of agenesis of the corpus callosum with the most severe manifestations in the most severely affected males. DNA analysis using a series of X‐linked probes suggests linkage with a LOD score of 1.26 at θ=0 to a region between p 11.3 and p 21.3.
New X‐linked syndrome with apraxia, ataxia, and mental deficiency: Clinical, cytogenetic and neuropsychological studies in two Danish families
Authors: Tranebjærg Lisbeth , Lou Hans , Andresen Jente
Published: June 2005

In 2 unrelated families 9 males presented with ataxia, apraxia, and neuropsychological abnormalities or mental deficiency, inherited as an X‐linked recessive syndrome with partial clinical expression in obligate female carriers. The symptoms were present in early childhood and were non‐progressive. Additional findings in 2 males were congenital “club‐feet” and generalized seizures. The affected males were 13‐62 years old at the time of our examination. Chromosome abnormalities including fragile X fra(X) could not be demonstrated in any case. Results of metabolic screenings were also normal. The clinical picture with X‐linked recessive inheritance distinguishes this syndrome from previously described inherited hereditary ataxias.
Incidence and associations of single umbilical artery in prenatally diagnosed malformed, midtrimester fetuses: A review of 62 cases
Authors: Csécsei Károly , Kovács Tamáa , Hinchliffe Stephen A. , Papp Zoltán
Published: June 2005

The absence of one umbilical artery (SUA) is the most common malformation of the umbilical cord. It may accompany other abnormalities or occur as an isolated defect. We examined 885 fetuses, terminated following the prenatal diagnosis of serious or lethal malformations between April 1977 and March 1989, for the presence of SUA. We found 62 cases of SUA. This represents an incidence of 7.01% (62/885). The most common abnormalities found in association with SUA were: (1) multiple malformations (8/11 cases, SUA incidence = 72.7%), (2) ADAM complex (7/14 cases, SUA incidence = 50.%), (3) multicystic renal dysplasia (5/20 cases, SUA incidence = 25.%), and (4) Potter sequence (5/21 cases, SUA incidence = 23.8%). These associations have not been documented previously. In 6 fetuses the Meckel syndrome was diagnosed, and SUA was present in 2 of these. Therefore, SUA may represent an additional anomaly in Meckel syndrome that has not been reported previously. © 1992 Wiley‐Liss, Inc.
Interstitial deletion of chromosome 16q: 16q22 is critical for 16q‐ syndrome
Authors: Fujiwara Masataka , Yoshimoto Toru , Morita Yasuyuki , Kamada Makoto
Published: June 2005

Partial deletion of 16q is rare; to our knowledge only 12 cases have been published. Fryns et al. [Hum Genet 38:343–346, 1977] described the first of these cases and proposed a new clinical entity. Our patient was a girl and had many minor anomalies of the kind often observed in 16q‐ syndrome. Severe failure to thrive due to emesis and diarrhea were also observed. High resolution banding methods showed that the chromosome constitution of the patient was 46,XX,del(16)(q22.1q22.3). This suggests that 16q22 is critical for the syndrome. © 1992 Wiley‐Liss, Inc.
New syndrome: Mental retardation, microbrachycephaly, hypotelorism, palpebral ptosis, thin/long face, cleft lip, and lumbosacral/pelvic anomalies
Authors: Richieri‐Costa A. , Guion‐Almeida M. L. , Ramos A. L.
Published: June 2005

We describe 2 Brazilian sisters with a combination of clinical signs strongly suggesting a new autosomal recessive MCA/MR syndrome. © 1992 Wiley‐Liss, Inc.
Transmission of the fra(X) haplotype from three nonpenetrant brothers to their affected grandsons
Authors: Kirkilionis A. J. , Chudley A. E. , Greenberg C. R. , Yan D. L. , McGillivray B. , Hamerton J. L.
Published: June 2005

We report on a family showing transmission of the fra(X) gene by 3 nonpenetrant, fra(X) negative, normally intelligent, full and half‐brothers to their affected grandsons. The mothers of the affected boys are obligate carriers, fra(X) negative, and of normal intelligence. This family illustrates the “Sherman Paradox” and is compatible with the predictions of the Laird X‐inactivation imprinting model. In addition molecular and/or cytogenetic studies have enabled at‐risk relatives to learn more about their carrier fra(X) status and have allowed for more accurate genetic counselling. © 1992 Wiley‐Liss, Inc.
Opitz (BBB/G) syndrome: Oral manifestations
Authors: Brooks John K. , Leonard Claire O. , Coccaro Peter J.
Published: June 2005

We studied a new case of the G (Opitz BBB/G) syndrome in a 12‐year‐old boy. Several relatives had partial manifestations of the disorder. A comprehensive dental evaluation of the propositus was conducted; included is, to our knowledge, the first published cephalometric analysis of a G syndrome patient. We reviewed 139 cases of the G syndrome; 48 of them had at least one oral abnormality. These included clefting, micrognathia, ankyloglossia, and high‐arched palate. Male G syndrome patients are more likely to have oral anomalies than affected females. © 1992 Wiley‐Liss, Inc.
Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: Review and delineation of the Cerebro‐Acro‐Visceral Early lethality (CAVE) multiplex syndrome
Authors: Verloes Alain , Gillerot Yves , Langhendries Jean‐Paul , Fryns Jean‐Pierre , Koulischer Lucien
Published: June 2005

We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty‐seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister‐Hall syndrome) and related diseases as Smith‐Lemli‐Opitz type II, holoprosencephaly‐polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister‐Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister‐Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. “Cerebro‐Acro‐Visceral Early lethality multiplex syndrome” is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed. © 1992 Wiley‐Liss, Inc.
Craniosynostosis associated with partial duplication of 15q and deletion of 2q
Authors: Van Allen M. I. , Siegel‐Bartelt J. , Feigenbaum A. , Teshima I. E.
Published: June 2005

We report on an infant with multiple congenital anomalies including complex craniosynostosis associated with an unbalanced karyotype, 46,XY, − 2, + der(2),t(2;15)(q37;q26)pat. The previous report of a child with cloverleaf skull and partial duplication of 15q25→qter and the Man‐on‐Mouse Homology map suggests that a critical segment for synostosis of sutures may be in this region. © 1992 Wiley‐Liss, Inc.
Cervical spine in the Apert syndrome
Authors: Kreiborg Sven , Barr Mason , Cohen M. Michael
Published: June 2005

Radiographs of the cervical spine—in many cases longitudinal—were available for study in 68 cases of Apert syndrome. Autopsy material was available in one of these cases, and a 3‐dimensional reconstruction from a CT scan was also studied in one case. Variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Ossification may not always be evident in some early radiographs. However, early radiographic signs of impending fusion may be irregularity in vertical orientation of the vertebral bodies and narrowing of the involved intervertebral spaces. Cervical fusions occurred in 68%, single fusions being found in 37%, and multiple fusions in 31%. C5−C6 fusion was most common, alone or in combination with other fusions. In contrast, cervical fusions are known to occur in 25% of Crouzon patients, most commonly involving C2−C3 only. It appears that when fusions are present, C5−C6 involvement in the Apert syndrome and C2−C3 involvement in the Crouzon syndrome separate the 2 conditions in most cases. Because cervical anomalies may complicate an already compromised airway in any form of acrocephalosyndactyly, it is imperative to initiate radiographic study of the cervical spine before undertaking anesthesia for surgery. © 1992 Wiley‐Liss, Inc.