bluuebunny/crossref_metadata_2025 huggingface dataset:
Dominant mesomelic dysplasia, ankle, carpal, and tarsal synostosis type: A new autosomal dominant bone disorder
Authors: Kantaputra Piranit N. , Gorlin Robert J. , Langer Leonard O.
Published: June 2005

A new type of mesomelic dysplasia was in 3 generations of a large Thai family. It is characterized by bilateral symmetrical marked shortening of the ulnae and shortening and bowing of the radii. The proximal fibula is usually short and synostoses are present between the tibia and fibula and the small malformed calcaneus and talus. The prominent calcanei on the ventral surfaces of the distal fibulae are a characteristic feature of the new type. Carpal and tarsal synostoses are present in some affected people. All affected individuals walk on the tips of their toes with the dorsal foot deviated laterally. The deformities of the radius and ulna somewhat resemble those of mesomelic dysplasia, Langer type, but otherwise the condition is distinctly different.

This new mesomelic dysplasia is an autosomal dominant trait with complete penetrance and variable expressivity over 3 generations. © 1992 Wiley‐Liss, Inc.
New hereditary malformation syndrome of unusual facial appearance, skeletal deformities, and musculoskeletal and sensory defects
Authors: Middleton L. T. , Anastasiades V. , Panayidou K. , Georghiou D. , Kalli E. , Gabriel G. , Myrianthopoulos N. C.
Published: June 2005

We report on a new syndrome characterized by specific and striking facial abnormalities, arthrogrypotic skeletal deformities, and neuromuscular and sensory defects in a large Greek Cypriot family. The hereditary transmission appears to be autosomal dominant with quite variable expressivity. © 1992 Wiley‐Liss, Inc.
Huntington disease in black Zimbabwean families living near the Mozambique border
Authors: Scrimgeour Euan M. , Pfumojena John W.
Published: June 2005

Huntington disease (HD) was identified in a black (Bantu) family living in the Manicaland region of Zimbabwe near the border with Mozambique. The pedigree included 11 affected individuals in 4 generations. There were 2 other probable HD patients from 2 unrelated black families in the same region. The prevalence rate of HD in this region of Zimbabwe was estimated to be 0.5–1 per 100,000. HD could have been introduced by Portuguese colonists from Mozambique, or by other European visitors, possibly before 1875. DNA studies may ultimately indicate if HD was introduced to this community, or if it arose by mutation. HD was previously reported in Zimbabwean blacks in 1978, when 4 cases of juvenile HD were described in a Bantu family with no apparent history of the disease. © 1992 Wiley‐Liss, Inc.
Chondrodysplasia punctata: Another possible X‐linked recessive case
Authors: Bennett C. P. , Berry A. Caroline , Maxwell D. J. , Seller Mary J.
Published: June 2005

A 22‐week fetus who had died in utero had a markedly hypoplastic nose and other facial abnormalities, short fingers, hypoplastic nails, and small phallus. Radiologically there was symmetrical cartilaginous stippling of the vertebral column, femoral heads, calcanei and elbows typical of chondrodysplasia punctata (CP), and metacarpal shortness and tiny pyramidal phalanges. The several causally different forms of CP are tabulated. Differential diagnosis suggests that the present case, which does not have limb shortness, could be a case of X‐linked recessive brachytelephalangic chondrodysplasia punctata. © 1992 Wiley‐Liss, Inc.
VATER/VACTERL association: Clinical variability and expanding phenotype including laryngeal stenosis
Authors: Corsello Giovanni , Maresi Emiliano , Corrao Anna Maria , Dimita Ubaldo , Cascio Manlio Lo , Cammarata Marina , Giuffrè Liborio
Published: June 2005

Vertebral abnormalities and anorectal and tracheoesophageal defects are the main manifestations in the VATER/VACTERL association. Radial defects vary from radial aplasia to thumb duplication. Heart and renal defects are reported with lower frequency. Additional malformations, such as the laryngeal stenosis described in the present patient, may expand the phenotype of the association. The wide spectrum of congenital abnormalities confirms the high clinical variability of VATER/VACTERL association which seems to be due to a disruption of blastogenesis. © 1992 Wiley‐Liss, Inc.
Infantile autism—fragile X: Molecular findings support genetic heterogeneity
Authors: Malmgren Helena , Gustavson Karl‐Henrik , Wahlström Jan , Arpi‐Henriksson Ingrid , Bensch Jurgen , Pettersson Ulf , Dahl Niklas
Published: June 2005

Twenty‐two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR‐1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR‐1 region in infantile autists negative for fragile X expression. © 1992 Wiley‐Liss, Inc.
Limb anomalies following chorionic villus sampling: A registry based case‐control study
Authors: Mastroiacovo Pierpaolo , Botto Lorenzo Davide , Cavalcanti Denise Pontes , Lalatta Faustina , Selicorni Angelo , Tozzi Alberto Eugenio , Baronciani Dante , Cigolotti Anna Chiara , Giordano Sergio , Petroni Fabio , Puppin Francesco
Published: June 2005

Using data from the Italian Multicentric Birth Defect Registry a case–control study was performed to verify if chorionic villus sampling (CVS) was associated with transverse limb defects (TLD), with or without features of oro–mandibular–limb hypogenesis complex (OMLHC), in the exposed offspring. The results show that the risk of TLD and OMLHC is increased following CVS, and is particularly high for CVS performed early in pregnancy, i.e., under 70 days of gestational age.

These results, together with a review of other epidemiologic studies, biological data and clinical reports, strongly suggest a causative role of CVS as a risk factor for TLD and indicate that at this stage CVS before 70 days of gestational age should be discouraged as an option for prenatal diagnosis and that all patients wishing to undergo CVS should be informed about the possible risk of the procedure. © 1992 Wiley‐Liss, Inc.
Pericentric inversion of chromosome 4 giving rise to dup(4p) and dup(4q) recombinants within a single kindred
Authors: Hirsch Betsy , Baldinger Shari
Published: June 2005

Theoretically, every pericentric inversion can give rise, during meiosis, to 2 alternate recombinant chromosomes. One of these will have a duplication of short arm material and deletion of long arm material (dup p), and the other, a duplication of a long arm material and deletion of short arm material (dup q). However, most published cases have been limited to a single recombinant type occurring within a given kindred. Here we document a large pericentric inversion of chromosome 4 which gave rise, within 2 generations of a kindred, to both dup p and dup q recombinants. The family was ascertained by the birth of a baby girl with multiple congenital anomalies suggestive of Wolf‐Hirschhorn syndrome, and was found to have a dup 4q recombinant. Subsequent studies of her father and of her 27‐year‐old mentally retarded aunt showed a balanced inv(4) (p15.32q35) and a dup 4p recombinant, respectively. Given that: (a) the balanced inversion involves approximately 87% of the length of chromosome 4; (b) the predicted meiotic pairing would be homosynapsis with loop formation; (c) the size of the segments distal to the breakpoints of the inversion are of similar and relatively small size; and (d) both recombinants are compatible with life, then the risk for recurrence of a recombinant in this family is high. Genetic counseling addressed these issues, and to date, both chronic villus sampling (CVS) and amniocentesis have been provided for prenatal diagnosis. © 1993 Wiley‐Liss, Inc.
Phenotype of cranioectodermal dysplasia with different hair and bone abnormalities
Authors: Lammer Edward J. , Baden Howard , Margolis Randall J.
Published: June 2005

We report on a 3‐year‐old boy with hair abnormalities and a generalized bone dysplasia. He had very short, sparse hair and craniosynotosis. His stature, growth, and limb lengths were normal, as was his neurological development. While this phenotype has some resemblance to cranioectodermal dysplasia, the radiographic and hair abnormalities are different. Histological studies showed abnormalities in the internal root sheath of the hair follicle and the hair shaft. These findings define a new ectodermal dysplasia syndrome of unknown cause. © 1993 Wiley‐Liss, Inc.
Fetal and neonatal outcome of exposure to anticoagulants during pregnancy
Authors: Wong V. , Cheng C. H. , Chan K. C.
Published: June 2005

We studied fetal and neonatal outcome of women maintained on anticoagulants (warfarin and/or heparin) during pregnancy. Among 22 Chinese families, 13 mothers (59%) had a history of recurrent abortion or stillbirth while being maintained on warfarin treatment. Twenty‐nine liveborn children (17 boys, 12 girls), ages 0.6–11.3 years at follow‐up, were analysed for evidence of embryopathy. These were subdivided into 2 groups. Group 1 consisted of 18 children (12 boys, 6 girls) whose mothers were only given warfarin during pregnancy. Five were small for gestational age, and 12 had features of warfarin embryopathy such as nasal hypoplasia. One had subependymal intraventricular hemorrhage shown on neonatal ultrasonography. Group 2 consisted of 11 children (5 boys, 6 girls) whose mothers were maintained on warfarin and heparin during pregnancy. Three were premature deliveries, and 4 had nasal hypoplasia. One had cleft lip, cleft palate, cataract, microphthalmia, intraventricular hemorrhage, and hydrocephalus. We found that despite the high risk of fetal wastage, there was a relative lower risk of major complications, except for some minor cosmetic defects such as nasal hypoplasia. This might lead to readjustment of advice concerning contraception given to pregnant women who were maintained on anticoagulant therapy. © 1993 Wiley‐Liss, Inc.
Characterization of a de novo 48,XX, + r(X), + r(17) by in situ hybridizatio in a patient with neurofibromatosis (NF1)
Authors: Wiktor Anne , Van Dyke Daniel L. , Weiss Lester
Published: June 2005

We describe a patient with familial neurofibromatosis (NF1), short stature, developmental delay, and a de novo chromosome abnormality. In sity hybridization was done using chromosome specific centromere probes to characterize the karyotype as 46,XX/47, XX,+r(X) (p11q11)/47,XX,+r(17) (p11q11)/48, XX,+r(X) (p11q11),+r(17) (p11q11). The NF1 mutation, as well as each superunmerary ring chromosome, may have played a role in perturbing the normal developmenal process of this patient. © 1993 Wiley‐Liss, Inc.
Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype
Authors: Park Jonathan P. , McDermet Malanie K. , Doody Ann M. , Marin‐Padilla J. Miguel , Moeschler John B. , Wurster‐Hill Doris H.
Published: June 2005

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley‐Liss, Inc.
Interstitial deletion of chromosome 2 region in a malformed infant
Authors: Melnyk A. R. , Muraskas J.
Published: June 2005

We describe an infant with a lumber meningomyelocele and other congenital anomalies and a de novo deletion of 2q36 with a nonmosaic karyotype 46,XX,del(2)(q36). © 1993 Wiley‐Liss, Inc.
Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome
Authors: Berry‐Kravis Elizabeth , Sklena Paul
Published: June 2005

Cyclic AMP production was studied in platelets from 31 patients with fragile X syndrome, 16 patients with mental retardation, 4 patients with autistic disorder, and 57 control individuals. 1‐isobutyl‐3‐methylxanthine (IBMX) was used to inhibit phosphodiesterase; prostaglandin E1 (PGE1), to stimulate cAMP production via a receptor‐dependent mechanism, and forskolin (FSK), to directly activate the catalytic subunit. Cyclic AMP production in IBMX, PGE1 + IBMX, and FSK + IBMX was 50% (P<0.05), 65% (P=0.001), and 53% (P = 0.001), respectively, in fragile X platelets relative to controls. Cyclic AMP production was not statistically different from controls in patients with mental retardation or autistic disorder. There was no effect of age or sex on cAMP production. Dose response curves suggested that abnormal cAMP production was due to diminished maximal response rather than altered potency of stimulating agents. The data presented here demonstrate that diminished cAMP production exists in platelets from patients with fragile X syndrome. Thus, defective functioning of cAMP‐mediated regulatory signalling pathways in fragile X brain may contribute to the mental deficiency in these patients. © 1993 Wiley‐Liss, Inc.
Stable inheritance of the CMT1A DNA duplication in two patients with CMT1 and NF1
Authors: Lupski James R. , Pentao Liu , Williams Lowell L. , Patel Pragna I.
Published: June 2005

Charcot‐Marie‐Tooth disease type 1A (CMT1A) was recently demonstrated to be associated with a large DNA duplication in 17p11.2p12. The gene for neurofibromatosis type 1 (NF1) or von Recklinghausen disease maps to 17q11.2. We have identified 2 unrelated patients who were diagnosed with both CMT1 and NF1. Molecular analysis of these patients demonstrated the presence of the CMT1A duplication and inheritance of this DNA rearrangement from a parent affected with CMT. Analysis of genomic DNA isolated from the neurofibroma removed from one of these patients showed the same 500 kb SacII junction fragment associated with the CMT1A duplication that was found in genomic DNA isolated from the blood. These results lend further support to the hypothesis that the CMT1A duplication is a stable DNA rearrangement. In addition, the molecular analysis of these 2 patients suggests that 2 common autosomal dominant conditions (CMT1 and NF1) can occur in the same individual, not because of an underlying single molecular defect, but rather, secondary to a chance phenomenon. © 1993 Wiley‐Liss, Inc.
Interstitial deletion of distal chromosome 4p in a patient without classical Wolf‐Hirschhorn syndrome
Authors: Estabrooks Laurel L. , Rao Kathleen W. , Korf Bruce
Published: June 2005

We report on a patient with a de novo interstitial deletion of chromosome 4p; 46,XY,del(4) (p15.31p16.3). The cytogenetic diagnosis would predict a patient with the Wolf‐Hirschhorn syndrome (WHS) since deletions of 4p16 are associated with WHS [Wilson et al., 1981]. This patient lacks the facial characteristics of WHS, but has some anomalies of WHS that are also commonly seen in other syndromes, i.e., severe growth retardation, developmental delay, and hypospadias. His molecular distal breakpoint occurs in 4p16.3 as defined by fluorescence in situ hybridization and Southern blot analysis, and his deletion does not overlap with the currently proposed WHS critical region. This case gives further support to the distal position of the WHS critical region and demonstrates some of the WHS associated phenotypes that can be attributed to a deletion of the proximal third of 4p16.3. © 1993 Wiley‐Liss, Inc.
Osteogenesis imperfecta: The distinction from child abuse and the recognition of a variant form
Authors: Paterson Colin R. , Burns James , McAllion Susan J.
Published: June 2005

Unexplained fractures are characteristic of both osteogenesis imperfecta (OI) and nonaccidental injury (NAI) but in most cases the diagnosis is straightforward. However, in a few OI patients an initial diagnosis of NAI is made. Factors contributing to such difficulties include failure to recognise that OI can occur without a family history, without blue sclerae, without osteopenia, an excess of Wormian bones, or with metaphyseal fractures.

In addition we report on 39 patients with an unusual history in that fractures only occurred in the first year of life. Rib fractures, metaphyseal abnormalities and periosteal reactions were common. The initial diagnosis was usually OI if the fractures occurred in hospital, but NAI if they appeared to have been sustained at home. Additional findings such as anaemia, vomiting, hepatomegaly, and apnoeic attacks were often found in these patients. The disorder has some similarities to the syndrome of infantile copper deficiency. Like the latter it is particularly common in preterm infants and in twins. Therefore, we are attempting to examine the incidence of significant hypocupraemia in unselected preterm infants.

We suggest that the likely cause of this “temporary brittle bone disease” is a temporary deficiency of an enzyme, perhaps a metalloenzyme, involved in the post‐translational processing of collagen.
Comprehensive rehabilitation of the child with osteogenesis imperfecta
Authors: Binder Helga , Conway Ann , Hason Stephen , Gerber Lynn H. , Marini Joan , Berry Roger , Weintrob Joan
Published: June 2005

Children with osteogenesis imperfecta (OI) that results in considerable deformity are often viewed as poor candidates for aggressive physical therapy and rehabilitation. To determine if this view is realistic, we have entered almost 50 children with OI type III and OI type IV into a comprehensive graduated rehabilitation program, based at the National Institutes of Health, but designed to be implemented by continuing involvement of community resources. Children are begun in the program early with emphasis on gain of head and trunk control and progression to sitting and walking, if possible, with the aid of a variety of phsysical supports, including internal and external bracing. Although not conducted in a randomized fashion, the program's success in bringing children into graded exercise regimes and fostering their increased involvement in school and social situations suggest that aggressive physical therpy and rehabilitation have a major place in the overall care of the infants and children with OI.
Early surgical management of severe forms of osteogenesis imperfecta
Authors: Cole William G.
Published: June 2005

The early surgical management of severe osteogenesis imperfecta (OI) was studied in three children with autosomal recessive type III form of this disease. Each child had similar clinical and radiographic features at birth. The spine, pelvis, and thorax were osteoporotic but were well formed and free of major fractures. In contrast, the peripheral skeleton was severely affected with numerous new and old fractures. Conservative treatment of fractures was undertaken with a foam mould for the torso and limbs and additional support was provided for specific unstable painful fractures. However, fractures continued due to the extreme bone fragility and deformities. Surgical correction of deformities and internal splinting of the long bones with intermedullary rods was commenced between 18 months and 5 years of age. The shafts of the long bones were extremely fragile and lacked cortical bone. The osteotomies were under‐taken with a scalpel. The fracture rate diminished rapidly but the non‐extending rods needed shortening or replacing within 2 to 3 years.

The combination of external and internal fixation and electric wheel chairs greatly reduced the frequency of fractures and facilitated the general care and development of these 3 children with a severe form of OI.
Long term survival of an infant with Sirenomelia
Authors: Clarke Lorne A. , Stringer David A. , Fraser Graham C. , Yong Siu Li
Published: June 2005

We report on a 3‐month‐old infant whose sirenomelia was diagnosed prenatally. The infant is neurologically normal and has “fusion” of the lower limbs with associated renal dysplasia, imperforate anus, pelvic and sacral “dysplasia,” and genital abnormalities. In addition she has a preauricular skin tag and rib fusion. The infant's anomalies are compatible with life and surgical separation of the lower limbs is planned. © 1993 Wiley‐Liss, Inc.
Familial Mediterranean fever in the colchicine era: The fate of one family
Authors: Zemer Deborah , Livneh Avi , Pras Mordechai , Sohar Ezra
Published: June 2005

In order to demonstrate the effect of prophylactic colchicine treatment on the natural history of familial Mediterranean fever (FMF), a family is presented with 6 out of 9 siblings affected by FMF. Each patient represents a different stage of the amyloidotic kidney disease of FMF and the effect of continuous colchicine treatment on its course. Considered together, the members of this family present an almost complete clinical, genetic, and behavioral picture of the disease. © 1993 Wiley‐Liss, Inc.
Michelin tire baby syndrome: Familial constriction bands during infancy and early childhood in four generations
Authors: Bass Harold N. , Caldwell Sibylle , Brooks Barry S.
Published: June 2005

We report on an infant with an unusual pattern of transitory familial constriction bands distributed symmetrically and circumferentially over the neck, forearms, and lower legs. Family history showed the occurrence of similar bands among individuals in 4 generations transmitted as an autosomal dominant trait. Neck and limb distribution in the other affected family members was also symmetrical and circumferential, with spontaneous resolution taking place during childhood. This case represents another example of the Michelin tire baby syndrome, also known as multiple benign circumferential skin creases of the limbs, and further demonstrates its autosomal dominant mode of inheritance. © 1993 Wiley‐Liss, Inc.
Extended major histocompatibility complex haplotypes in celiac patients in the west of Ireland
Authors: Mannion Anne , Stevens Fiona M. , McCarthy C. F. , Grimes‐O'Cearbhaill Helen , Killeen A. A.
Published: June 2005

The highest reported prevalence of celiac disease (gluten‐sensitive enteropathy) is found in the West of Ireland. Recent genetic data have suggested that major histocompatibility complex‐linked loci may have a dominant genetic effect for disease susceptibility in this population compared with a recessive effect in other groups. To further understand the role of the MHC in celiac disease in the West of Ireland, we analyzed markers for 22 MHC haplotypes from celiac patients and compared them with 18 nontransmitted haplotypes found in the parents of celiac children, and with reported haplotypes from other populations. An extended MHC haplotype including [HLA‐B8, DR3, DQw2, Bf*S, C4A*Q0, and C4B*1] accounted for 50% of celiac haplotypes but only 27% of nontransmitted parental haplotypes. Compared with other reported haplotypes in celiacs, patients from the West of Ireland show a higher prevalence of HLA‐A1 as a component of this extended haplotype, suggesting that although the core haplotype is similar between Irish patients and others, the celiac population in the West of Ireland differs at other HLA loci. We did not observe any other common haplotypes among our patients unlike the situation in other populations. These differences may underlie the possible dominant effect of HLA‐linked loci and the unusually high prevalence of celiac disease in the Irish population. We also found that the serum levels of complement components C3c, C4, and factor B were significantly lower among celiac patients than nonceliacs. The lower serum level of C4 appears to be related to the presence of deletions and null alleles at the C4A and C4B loci in celiacs. © 1993 Wiley‐Liss, Inc.
Prenatal diagnosis of Tetraploidy: A case report
Authors: Coe Sandra J. , Kapur Raj , Luthardt Frederick , Rabinovitch Peter , Kramer Dawna
Published: June 2005

We report on the second trimester prenatal diagnosis of an apparently nonmosaic tetraploid fetus, 92,XXYY. Indications for cytogenetic studies of the fetus included abnormal ultrasound findings and abnormal maternal serum levels of alpha‐fetoprotein (AFP)/human chorionic gonadotropin (hCG)/estriol. Chromosome analysis of amniocytes documented tetraploidy, a finding confirmed by flow cytometry of several fetal tissues. Autopsy findings in the fetus are compared with those of other cases of tetraploidy. To our knowledge this is the first reported prenatal diagnosis of a tetraploid fetus. Additionally, it illustrates the value of flow cytometric analysis of products of conception in which polyploidy is suspected. © 1993 Wiley‐Liss, Inc.
Decrease in the size of the myotonic dystrophy CTG repeat during transmission from parent to child: Implications for genetic counselling and genetic anticipation
Authors: Hunter Alasdair G. W. , Jacob Pierre , O'Hoy Kim , MacDonald Ian , Mettler Gabrielle , Tsilfidis Catherine , Korneluk Robert G
Published: June 2005

Recently an unstable trinucleotide CTG repeat, located within the 3′ untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age‐of‐onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM.

In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data. © 1993 Wiley‐Liss, Inc.
Eye abnormalities in the Smith‐Magenis contiguous gene deletion syndrome
Authors: Finucane Brenda M. , Jaeger Edward R. , Kurtz Michael B. , Weinstein Martha , Scott Charles I.
Published: June 2005

We present the results of ophthalmologic assessment in 10 patients with interstitial chromosome deletions of 17p11.2, otherwise known as the Smith‐Magenis syndrome (SMS). The most common abnormalities noted were strabismus, Brushfield spots, high myopia, and retinal detachments. We have previously reported high myopia and retinal detachments in 6 patients with SMS (Finucane et al.: Am J Hum Genet 49:262A, 1991). We present additional details on these individuals, as well as findings in 4 newly reported patients. Ocular pathology appears to be very common in SMS, significantly contributing to disability in people with this syndrome. The combination of high myopia, self‐injurious head‐banging, aggression, and hyperactivity among these patients makes them particularly susceptible to retinal detachments. Detailed ophthalmologic assessment should be included in the clinical work‐up and monitoring of all patients with SMS resulting from deletion 17p11.2. © 1993 Wiley‐Liss, Inc.
Mosaicism for deletion 17p11.2 in a boy with the Smith‐Magenis syndrome
Authors: Finucane Brenda M. , Kurtz Michael B. , Ramesh Babu V. , Scott Charles I.
Published: June 2005

We describe a 14‐year‐old boy with physical and behavioral manifestations of the Smith‐Magenis syndrome. Low level mosaicism (11%) for deletion 17p11.2 was found in peripheral blood lymphocytes. The deletion was also observed in 100% of metaphases examined from skin fibroblast cultures. We confirm that the Smith‐Magenis syndrome is associated with a highly recognizable phenotype. Because evidence of the abnormal cell line may be minimal or absent in peripheral blood, fibroblast studies are indicated for patients in whom mosaicism for deletion 17p11.2 is suspected clinically. © 1993 Wiley‐Liss, Inc.
Further delineation of spondylo‐meta‐epiphyseal dysplasia, short limb‐abnormal calcification type, with emphasis on diagnostic features
Authors: Langer Leonard O. , Wolfson Barbara J. , Scott Charles I. , Reid Cheryl S. , Schidlow Daniel V. , Millar Edward A. , Borns Patricia F. , Lubicky John P. , Carpenter Becky L. M.
Published: June 2005

Further delineation of a generalized bone dysplasia which we call spondylo‐meta‐epiphyseal dysplasia, short limb‐abnormal calcification type is presented. This dwarfing condition has several serious complications, with the most common cause of death being spinal cord damage secondary to atlantoaxial instability. It is a heritable condition with an autosomal recessive mode of transmission. Radiologic diagnostic criteria are developed on the basis of studies in 8 patients with the oldest being between 4 and 5 years old. The condition is clinically and radiographically apparent neonatally or in early infancy, and it is probable that all or almost all affected individuals will come to medical attention in the age range screened by this study. © 1993 Wiley‐Liss, Inc.
Further delineation of the Baller‐Gerold syndrome
Authors: Lin Angela E. , McPherson Elizabeth , Nwokoro Ngozi A. , Clemens Michele , Losken H. Wolfgang , Mulvihill John J.
Published: June 2005

Three new patients with the Baller‐Gerold syndrome bring the number of reported cases to 20. In addition to craniosynostosis involving various sutures and preaxial reduction defects of variable severity, affected patients may have anal, urogenital, cardiac, central nervous system, and vertebral defects. Autosomal recessive inheritance is supported by the presence of affected sibs and parental consanguinity. © 1993 Wiley‐Liss, Inc.
Joubert syndrome associated with Leber amaurosis and multicystic kidneys
Authors: Ivarsson Sten‐A. , Bjerre Ingrid , Brun Arne , Ljungberg Otto , Maly Eva , Taylor Ingrid
Published: June 2005

We describe a boy with manifestations of Joubert syndrome, Leber congenital amaurosis, and multicystic kidneys. In infants with unexplained neonatal tachypnea and late developmental delay, absence or hypoplasia of the cerebellar vermis should be sought. Joubert syndrome probably is an autosomal recessive disorder. In the subsequent pregnancy of the propositus' mother, we were able to make a prenatal diagnosis of Joubert syndrome, one of the first to be reported. © 1993 Wiley‐Liss, Inc.
Hearing loss and temporal bone structure in achondroplasia
Authors: Shohat Mordechai , Flaum Eugene , Cobb Steven R. , Lachman Ralph , Rubin Cathi , Ash Carol , Rimoin David L.
Published: June 2005

Characteristic temporal bone changes have recently been defined by high resolution CT in nine patients with achondroplasia (Cobb et al., Am J Neuroradiol 9:1195, 1988). These included narrowing of the skull base and “;towering”; petrous ridges resulting in abnormal orientation of the inner and middle ear structures. In order to determine whether these morphologic changes are the cause of the hearing deficit in achondroplasia, audiometric studies and ENT evaluation were performed in eight of the nine patients. All had a history of frequent otitis media and four had experienced tympanic membrane tube insertion. Three patients had significant sensorineural hearing loss, two had conductive hearing loss and one patient had combined hearing loss. None of the temporal bone morphologic changes were found to be correlated with the degree of either sensorineural or conductive hearing loss. Fusion of the ossicular chain was not present in any of our cases. Appropriate treatment of frequent acute otitis media and early awareness of middle ear effusions and conductive hearing loss in children with achondroplasia may be of great importance in preventing permanent hearing loss. © 1993 Wiley‐Liss, Inc.
Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers
Authors: Haworth J. C. , Dilling L. A. , Surtees R. A. H. , Seargeant L. E. , Lue‐Shing H. , Cooper B. A. , Rosenblatt D. S.
Published: June 2005

We describe two brothers with 5,10‐methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years. Both had homocystinuria and homocystinemia and low plasma levels of methionine. MTHFR activities in cultured skin fibroblasts of both patients were <10% control and residual enzyme activities were markedly reduced on heating. The parents had intermediate enzyme activities and the reductase in the father (who had unexplained paraparesis and homocystinemia), but not in the mother, was also thermolabile. Both patients were treated with oral folate and betaine which improved, but did not totally correct, their biochemical abnormality. MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults. © 1993 Wiley‐Liss, Inc.
46,XY/47,XYY male with the fragile X syndrome: Cytogenetic and molecular studies
Authors: Milunsky Aubrey , Huang Xinli , Amos Jean A. , Herskowitz Joel , Farrer Lindsay A. , Wyandt Herman E.
Published: June 2005

We report the first case of a 46,XY/47,XYY mosaic male with fragile X[Fra(X)] expression in both cell lines. Cytogenetic analysis, DNA linkage analysis, and direct detection of the pre‐ and full mutation for the affected individual and his at‐risk female relatives were performed. Southern analysis of PstI‐digested DNA with probe pX6 clearly distinguished the normal genotype, the premutation, and the full mutation in various individuals in the patient's family. Fra(X) carriers who had normal cytogenetic results were clearly identified by direct mutation analysis. © 1993 Wiley‐Liss, Inc.
Autosomal dominant multiple café‐au‐lait spots and neurofibromatosis‐1: Evidence of non‐linkage
Authors: Charrow Joel , Listernick Robert , Ward Kenneth
Published: June 2005

Multiple café‐au‐lait spots have been observed in successive generations of several families without any other manifestations of neuro‐fibromatosis (NF) or any other systemic disorder. The café‐au‐lait spots in these families segregate as an autosomal dominant trait. The relationship (if any) between the gene for this trait and the NF‐1 gene has previously been unknown. We describe a family with five individuals spanning four generations with dominantly inherited café‐au‐lait spots, without any other stigmata of NF‐1. Linkage analysis with probes proximal, distal, and within the NF‐1 gene indicate that the trait in this family is not linked to NF‐1. We propose that this condition be called Familial Café‐Au‐Lait Spots (FCAL) to distinguish it from the neuro‐fibromatosis syndromes. © 1993 Wiley‐Liss, Inc.
Varying neurological phenotypes among mut° and mut− patients with methylmalonylCoA mutase deficiency
Authors: Shevell Michael I. , Matiaszuk Nora , Ledley Fred D. , Rosenblatt David S.
Published: June 2005

MethylmalonylCoA mutase (MCM) is a mito‐chondrial homodimer responsible for the isomerization of methylmalonylCoA to succinylCoA. Apomutase defects are traditionally divided into mut° and mut− classes on the basis of residual mutase activity. Clinical findings were reviewed in 20 patients with methylmalonic aciduria secondary to MCM deficiency. All 11 mut° patients had an early neonatal presentation; 6 of these patients died in infancy and 3 of 5 survivors had a poor neurological outcome as evidenced by severe delay or spastic quadriparesis with dystonia. The 2 other survivors include a 27‐month‐old child with a mild delay in verbal and fine motor skills and an adolescent with low normal intelligence. Of the 9 mut− patients, 7 became symptomatic in late infancy or childhood and 2 were picked up on screening. Two of the 9 patients have never had an episode of metabolic decompensation yet both are neurologically compromised; one severely retarded and autistic, the other mildly delayed. Four mut− patients have had episodic acidosis and are neurologically moderately affected, while 3 have had episodic acidosis and are neurologically intact. These results confirm phenotypic pleomorphism without a consistent pattern of neurological injury and suggest some broad correlation between mutase class and phenotype. Survival with good outcome is possible among mut° patients as is significant morbidity among mut− patients. Acidosis and metabolic imbalance are not necessary preconditions for significant morbidity. © 1993 Wiley‐Liss, Inc.
Monozygotic twins concordant for Rubinstein‐Taybi syndrome and implications for genetic counseling
Authors: Robinson Tonya W. , Stewart Dan L. , Hersh Joseph H.
Published: June 2005

We report on a set of monozygotic twin boys concordant for Rubinstein‐Taybi syndrome, and discuss the possible genetic basis of the disorder. © 1993 Wiley‐Liss, Inc.
Rare alpha 1 antitrypsin allele PI W and a history of infant liver disease
Authors: Clark Dr. P. , Chong A. Y. H.
Published: June 2005

We present a consanguinous couple whose three of four children are homozygous for a rare slow alpha 1 antitrypsin allele PI*W. All three children had abnormal liver function in infancy and two died in infancy of liver disease. The eldest child and both parents were heterozygous for the PI*W allele and were unaffected. Therefore, although serum levels are not markedly reduced, homozygotes appear to be at increased risk of developing liver disease. © 1993 Wiley‐Liss, Inc.
Paternal age as a risk factor for Down syndrome
Authors: de Michelena María I. , Burstein Ezra , Lama Javier R. , Vásquez Julio C.
Published: June 2005

Although the effect of maternal age as a risk factor for Down syndrome (DS) is well known, the role of paternal age in the cause of DS has not been clearly established. To investigate this phenomenon we conducted a case‐control study between July 1989 and February 1990. The cases were 318 children and teenagers with DS studied at the Specialized Educational Institutions of Lima City, Perú. They were paired with 1,196 control individuals that were selected from the birth records of 2 general hospitals of the city. For each case we tried to obtain 4 controls, paired by their date of birth, sex, and maternal age. The means of paternal age in the 2 groups were compared, first globally and then by groups of maternal age (<21 years, 21–29 years, 30–34 years, 35–39 years and >39 years). None of the comparisons gave a statistically significant difference between the 2 groups, using either the Student t‐test or the Mann‐Whitney U‐test. The results obtained in this study give no evidence that paternal age can be considered a risk factor for the conception of a child with DS. © 1993 Wiley‐Liss, Inc.
Craniofacial, limb, and abdominal anomalies in a distinct syndrome: Relation to the spectrum of Pfeiffer syndrome type 3
Authors: Barone Constance M. , Marion Robert , Shanske Alan , Argamaso Ravelo V. , Shprintzen Robert J.
Published: June 2005

Presented are 2 patients with abnormal craniofacial region, limbs, and abdomen, features that may be consistent with Pfeiffer syndrome, type 3. Both patients had bicoronal and bisphenoidal synostosis, extreme exophthalmic midface hypoplasia, and hydrocephalus. The limbs had a fixed flexion deformity of the elbows with broad thumbs which were radiopalmarly deviated; the toes were broad with a varus deformity and syndactyly of toes 2–5. Both patients developed bowel obstruction secondary to midgut malrotation, and one of the patients had prune belly syndrome. Review of the literature disclosed an additional patient who, in retrospect, had Pfeiffer syndrome type 3 and midgut malrotation. These patients suggest that intestinal malrotation with or without prune belly syndrome may be a common component of this entity. © 1993 Wiley‐Liss, Inc.
Brachydactyly, mesomelia, mental retardation, aortic dilatation, mitral valve prolapse, and characteristic face
Authors: Stratton Robert F. , Garcia Patricia R. , Young Robert S. , Jorgenson Ronald J.
Published: June 2005

We report on a male with brachydactyly, thin habitus with narrow shoulders, mesomelic shortness of the arms, long lower face with obtuse mandibular angle, maxillary hypoplasia with beaking of the nose, aortic root dilatation, and mitral valve prolapse. This combination of findings has not been reported previously. © 1993 Wiley‐Liss, Inc.
Dir dup(X) (q13→qter) in a girl with growth retardation, microcephaly, developmental delay, seizures, and minor anomalies
Authors: Aughton David J. , AlSaadi Abdul A. , Johnson Judith A. , Transue David J. , Trock Gary L.
Published: June 2005

In males, duplication of a portion of Xq is associated with multiple congenital anomalies and developmental delay. Most females recognized as having dup(Xq) are phenotypically apparently normal relatives of phenotypically abnormal males; phenotypic normalcy has been attributed to selective inactivation of the duplicated X chromosome. Heretofore, apparently only 5 distinctly phenotypically abnormal females with dup(Xq) have been reported. We report on a 3‐years‐old girl with developmental delay, growth retardation, microcephaly, minor anomalies, and a seizure disorder who had a nonmosaic, de novo direct duplication of the terminal portion of one X chromosome. In each of 50 lymphocytes examined, the duplicated X chromosome was found to be late‐replicating. This case shows that selective inactivation (as reflected by late replication) of the duplicated X chromosome does not inevitably confer phenotypic normalcy on females with dup(Xq), and suggests that other mechanisms must account for the phenotypic differences observed among females with dup(Xq), such as expression of recessive genes on the acive X chromosome, incomplete inactivation of some portion of the duplicated inactivation of some portion of the duplicated chromosomal segment, an imprinting effect, or some combination of these. © 1993 Wiley‐Liss, Inc.
Segregation analysis of rare autosomal folate sensitive fragile sites
Authors: Samadder Pranati , Evans Jane A. , Chudley Albert E.
Published: June 2005

We have studied 12 families with rare autosomal folate sensitive fragile sites (RAFSFS). Of these, 9 were informative for segregtion analysis of fragile sites in order to assess differences in parental transmission. We identified 20 families with RAFSFS from the literature from 1985 to 1989; thirteen of these were informativ for segregation analysis.

Segregation analysis confirmed that paternal fragile site transmission rates deviated significantly from the expected 50% for a Mendelian co‐dominant trait. Sex ratio comparisons showed a significant excess of transmitting females and a significnt excess of males among fragile site non‐carriers from the literature families. Comparison of the fragile site carriers with non‐carriers in the combined data showed a non‐significant excess of non‐carriers.

We confirmed a deficiency of offspring expressing fragile sites when trnsmission was through fathers, suggesting gametic selection or the phenomenon of parental genomic imprinting. © 1993 Wiley‐Liss, Inc.
Index finger hyperphalangy and multiple anomalies: Catel‐manzke syndrome?
Authors: Wilson Golder N. , King Teresa E. , Brookshire Gail S.
Published: June 2005

We describe a boy with short stature, develpmental delay, unusual face, right iris coloboma, malformed ears, micrognathia, and skeletal anomalies including hyperphalangy of the index fingers, bilateral fifth finger clinodactyly, short halluces, and scoliosis. Internal anomalies included asymmetric and dilated cerebral ventricles and ventricular septal defect. The Neonatal history of small jaw with feeding and respiratory difficulties suggested a Pierre Robin sequence, but there was no cleft palate. Two maternal uncles with similar anomalies had died at ages 13 months and 5 years, respectively, RFLP studies with the DNA probes DXS72 and F8C were consistent with but not diagnostic of X‐linked recessive inheritance. The pattern of anomalies was compatible with a diagnosis of Catel‐Manzke syndrome, but a novel dysostosis syndrome must also be considered. © 1993 Wiley‐Liss, Inc.
Bromodeoxyuridine induces chromosomal fragile sited in the canine genome
Authors: Stone Diana M. , Stephens Kimberly E.
Published: June 2005

Peripheral blood lymphocytes from 3 clinically normal domestic dogs were cultured for bromodeoxyuridine (BrdU) induction of fragile site expression. BrdU induced fragile site expression in cells from all 3 dogs. The mean percent of cells with fragile sites and the mean number of fragile sites per cel were significantly increaed in all BrdU incubated cultures compared to control cultures. The frequency of BrdU fragile site expression did not vary significantly among the dogs. Lymphocytes from all 3 dogs expressed BrdU induced autosomal fragile sites. Two BrdU induced fragile sites were identified on the long arm of chromosome 1, one of which was close to or coincident with a previously identified folate sensitive fragile site on this canine chromosome. Lymphocytes from the 2 female dogs also expressed BrdU induced fragile sites on the X chromosome, but BrdU failed to induce fragile sites on the X chromosome from the one male dog in the study. The 2 BrdU‐induced fragile sites identified on the long arm of the X chromosome were close to, or coincident with 2 previously described folate‐sensitive common fragile sited on the canine X chromosome. This is the fist report of induction of BrdU‐inducible fragile sites in the genome of the domestic dog. © 1993 Wiley‐Liss, Inc.
Long‐term outcome of Hurler syndrome following bone marrow transplantation
Authors: Whitley Chester B. , Belani Kumar G. , Chang Pi‐Nian , Summers C. Gail , Blazar Bruce R. , Tsai Michael Y. , Latchaw Richard E. , Ramsay Norma K. C. , Kersey John H.
Published: June 2005

Previous reports suggested a therapeutic response of lysosomal storage diseaes such as Hurler syndrome following bone marrow transplantation. However, a clearer understanding of outcome has awaited long‐term follow‐up. We evaluated prospectively 11 consecutive patients with Hurler syndrome receiving marrow from an HLA‐identical sib donor between September 1983–October 1988. Follow‐up evaluations included assessment of donor engraftment by restriction fragment polymorphism analysis, determination of leukocyte α‐L‐iduronidase level, Measurement of lumbar cerebrospinal fluid (CSF) pressure, computerized tomography (CT) of the brain, and psychometric testing. In this series there was survival rate of 9/11 (82%) with all survivors showing complete (7 patients) or partial (2 patients) donor engraftment. Prospective longitudinal evaluation of the 9 surviving children, now 3.8–8.9 years posttransplantation (median 5.5) demonstrated persistence of previously deficient leukocyte α‐L‐iduronidase at levels reflecting the donor genotype and degree of dono engraftment. Urinary glycosaminoglycan excretion declined to near‐normal within 5 months of donor engraftment. Prior to treatment, 7 of 8 children studied were found to have occult intracranial hypertension (lumbar CSF pressurse < 20 cm CSF); however, all surviving children attained normal or near‐normal pressure within 18 months of donor engraftment. Long‐term follow‐up CT imaging of the brain did not show progressive volume loss (cerebral atrophy) after donor engraftment. Of 9 survivors, 4 children having a developmental quotient (DQ, Mental Development Index on Bayley Scales of Infant Development) above 80 prior to transplantation subsequently maintained IQ scores above this level. However, 5 patients with lower pretransplant DQ scores now have significant cognitive deficits and attention deficit hyperactivity disorder. Progressive brain damage resulting from communicating hydrocephalus may be prevented by successful engraftment. Early transplantation of children with Hurler syndrome who have normal intelligence is likely to have the clearest benefit becaue long‐term intellectual outcome will be limited by brain damage which has occurred prior to treatment. © 1993 Wiley‐Liss, Inc.