bluuebunny/crossref_metadata_2025 huggingface dataset:
Caroline crachami, the sicilian fairy: A case of bird‐headed dwarfism
Authors: Bondeson Jan
Published: June 2005

One of the most remarkable cases of extreme dwarfism on record is Caroline Crachami, the Sicilian Fairy. She was born in 1815, and was taken to London to be exhibited for money in 1824. Due to her proportional dwarfism, severe intrauterine growth retardation, and typical “bird‐headed” profile, Caroline Crachami has by some been diagnosed as a case of the autosomal recessive Seckel syndrome. In this historical vignette, the Sicilian Fairy's life and death are presented in some detail using new material, and the problem of her correct diagnosis is discussed. © 1992 Wiley‐Liss, Inc.
6p23 Deletion mosaicism in a woman with recurrent abortions and idiopathic hypoprolactinemia
Authors: D'Alessandro Elvira , Santiemma Vittorio , Re Maria Luisa Lo , Ligas Claudio , Del Porto Giuseppe
Published: June 2005

A woman with a history of recurrent abortions, idiopathic hypoprolactinemia, and an apparent 6p partial deletion mosaicism is described. The breakpoint in the short arm of chromosome 6 was in the p23 region. This deletion could have been caused by a fragile site in 6p23. © 1992 Wiley‐Liss, Inc.
Further evidence for dominant inheritance at the chromosome 15q11‐13 locus in familial angelman syndrome
Authors: Clayton‐Smith J , Webb T , Robb S A , Dijkstra I , Willems P , Lam S , Cheng X‐J , Pembrey M E , Malcolm S
Published: June 2005

Eleven patients with Angelman syndrome (AS) and their parents from 5 families have been studied with high resolution chromosome analysis and molecular probes from region 15q11‐13 in an attempt to elucidate the mode of inheritance in familial AS. No deletions were detected. All families were informative with a combination of different short arm cytogenetic markers. All sets of sibs inherited the same maternal chromosome 15, but in 3 families sibs inherited different paternal 15s. Analysis of 6 polymorphic DNA markers supported the conclusion that AS sibs inherit the same maternal 15, but often different paternal 15s. These data make autosomal recessive inheritance at a 15q11‐13 locus very unlikely and support the hypothesis that familial AS is due to maternal transmission of a mutation within 15q11‐13. © 1992 Wiley‐Liss, Inc.
Cystic kidney dysplasia and polydactyly in 3 sibs with Bardet‐Biedl syndrome
Authors: Gershoni‐Baruch Ruth , Nachlieli Tal , Leibo Rina , Degani Shimon , Weissman Irith
Published: June 2005

Two infants with cystic kidney dysplasia and polydactyly were born to consanguineous parents. One infant died at age 2 months, and the other is currently 3.5 years old. A third pregnancy was terminated following ultrasonographic visualization of large echodense fetal kidneys and polydactyly. Although none had apparent brain anomalies, they were considered to represent the Meckel syndrome. Extinguished responses on electroretinography in our 3.5‐year‐old patient has led to the diagnosis of Bardet‐Biedl syndrome. This observation offers an opportunity to revisit the Bardet‐Biedl syndrome and provides further evidence that structural renal abnormalities are characteristic of the syndrome. We wish to alert the clinician to the diagnosis of Bardet‐Biedl syndrome in patients with infantile cystic kidney dysplasia. © Wiley‐Liss, Inc.
Bannayan‐Riley‐Ruvalcaba syndrome
Authors: Gorlin Robert J. , Cohen M. Michael , Condon Lawrence M. , Burke Barbara A.
Published: June 2005

Here we report on 12 affected members of a family with Bannayan‐Riley‐Ruvalcaba syndrome. We present clinical evidence of overlap between Bannayan‐Zonana syndrome. Riley‐Smith syndrome, and Ruvalcaba‐Myhre syndrome in this autosomal dominantly inherited condition. We expand the phenotypic spectrum to include Hashimoto thyroiditis, which occurred in 7 of our cases. Finally, we discuss the relationship between the syndrome and juvenile polyposis of infancy. © Wiley‐Liss, Inc.
Asymmetry quantification utilizing hand radiographs
Authors: McLeod D. Ross , Coupland Stuart G.
Published: June 2005

Asymmetry can be either directional or fluctuating. Detection of abnormal amounts of asymmetry has important implications for clinical diagnosis, but measurement of subtle levels is very difficult. We describe a method and normative values for asymmetry quantification using hand radiographs. © Wiley‐Liss, Inc.
Application of the health belief model in a study on parents' intentions to utilize prenatal diagnosis of cleft lip and/or palate
Authors: Sagi Michal , Shiloh Shoshana , Cohen Tirza
Published: June 2005

Parents of children with cleft lip and/or palate (42 women and 35 men) participated in a study on intentions to use prenatal diagnosis of cleft by ultrasound in subsequent pregnancies. Based on the Health Belief Model (HBM) [Rosenstock, 1974], parents' cognitions on 4 factors were measured by questionnaires: “susceptibility” and “severity perceptions,” “benefits” and “barriers” evaluations. Most parents perceived the defect as severe. Overestimation of recurrence risks was predominant even among parents who had received genetic counseling. Results showed that most parents intend to utilize prenatal diagnosis but do not intend to abort an affected fetus. Subjects' reported reasons represented 3 thematic categories: cognitive (the need to know), emotional, and behavioral. Parents' intentions to diagnose and to terminate were related to the factors predicted by the HBM model. Regression analyses indicated that 38% of the variance in intentions to diagnose and 56% of the variance in intentions to terminate could be explained by the studied variables. The best predictor of both intentions was the perceived benefits of the diagnosis. Implications of these findings for genetic counseling are discussed. © Wiley‐Liss, Inc.
Case of ovarian dysgenesis and dilated cardiomyopathy supports existence of malouf syndrome
Authors: Narahara Kouji , Kamada Masahiro , Takahashi Yukio , Tsuji Kazushiro , Yokoyama Yuji , Ninomiya Shinsuke , Seino Yoshiki
Published: June 2005

We describe an 18‐year‐old girl with ovarian dysgenesis, dilated cardiomyopathy, mild mental retardation, broad nasal base, blepharoptosis, and minor skeletal abnormalities. This unusual association of manifestations was first reported by Malouf et al. [1985]. Our patient, although a sporadic case, supports the existence of Malouf syndrome. © Wiley‐Liss, Inc.
Utilization and evaluation of living‐related donors for patients with adult polycystic kidney disease
Authors: Hannig Vickie L. , Erickson Susan M. , Phillips John A.
Published: June 2005

Adult onset polycystic kidney disease (ADPKD) cause 10% of all end‐stage renal disease in the United States. Use of living‐related donors for renal transplants provides significant advantages over cadaver donors. Presymptomatic testing to determine ADPKD status of potential donors by DNA linkage analysis is potentially more accurate than renal ultrasonography for related donors < 30 years old. To determine the utilization of living donor transplants and linkage studies, a survey was mailed to 202 transplant centers in the United Network of Organ Sharing. The 111 respondents reported 5,026 renal transplants done in 1988 of which 390 (7.8%) involved an ADPKD recipient. Only 7% of these 390 transplants utilized a living‐related donor compared to the 20% rate reported for all renal transplants. DNA linkage studies were not used by any of the centers performing related donor transplants in 1988 and only 29% reported provision of risk counseling. We conclude that living‐related transplants are underutilized for ADPKD recipients due to conservative transplant policies, concern about the inaccuracy of presymptomatic diagnosis, or decreased availability of asymptomatic donors in these families. DNA linkage analysis is also underutilized due to lack of knowledge of its availability and accuracy, concerns about its cost and misconceptions about the accuracy of ultrasonography. Since the accuracy of molecular genetics techniques for presymptomatic diagnosis of ADPKD continues to improve and because transplants from living‐related donors convey significant advantages to recipients over cadaver transplants, we recommend that (1) a living‐related transplant be considered when feasible for ADPKD patients, (2) genetic counseling and DNA linkage analysis for presymptomatic testing be utilized for related donors when applicable, and (3) communication be improved between renal transplant and genetic centers.
Neonatal hemochromatosis: Genetic counseling based on retrospective pathologic diagnosis
Authors: Ferrell Linda , Schmidt Kathleen , Sheffield Val , Packman Seymour
Published: June 2005

We report a case of neonatal hemochromatosis in which the genetic counseling was initiated by, and based on, retrospective pathologic diagnosis. Perinatal or neonatal hemochromatosis is beginning to be recognized as a distinct clinical entity and one of the most common causes of perinatal cirrhosis. The exact mechanism of liver damage and the relationship to adult type hemochromatosis have not been fully clarified. The pattern of fibrosis in the liver plus the abundant iron deposition in the liver and other organs separate this entity pathologically from other causes of neonatal liver failure. We report on a case of neonatal hemochromatosis that was diagnosed on retrospective autopsy review of an infant with supposed hereditary tyrosinemia, when the family presented for genetic counseling. This case emphasizes to the genetic counselor and pathologist the need to consider the diagnosis prenatally, after birth, or at death, as failure to do so would result in the inability to identify families at genetic risk for neonatal hemochromatosis or in mislabeling a family with another inborn error.
Comparison of phenylketonuric and nonphenylketonuric sibs from untreated pregnancies in a mother with phenylketonuria
Authors: Levy Harvey L. , Lobbregt Deborah , Sansaricq Claude , Snyderman Selma E.
Published: June 2005

Two children, one with phenylketonuria (PKU) and the other nonphenylketonuric, from untreated pregnancies in a mother with PKU provided the opportunity to compare the degree of damage from maternal PKU between these genotypically different fetuses. Both the phenylketonuric offspring and her nonphenylketonuric sib were microcephalic at birth and had congenital anomalies, esophageal atresia in the former and congenital dislocation of the hip in the latter. However, the phenylketonuric child also had intrauterine growth retardation while the non‐phenylketonuric sib had normal weight and length at birth. Both children are mentally retarded with an IQ below 50 in the phenylketonuric child despite early dietary treatment for PKU and an IQ of 54 in the non‐phenylketonuric sib. Both children also have hypoplasia of the corpus callosum and enlarged cerebral ventricles. This experience and review of the literature indicates that the residual liver phenylalanine hydroxylase activity of a nonphenylketonuric fetus offers little or no protection from damage in untreated maternal PKU. Consequently, the outcome in maternal PKU is likely to depend on control of the maternal biochemical abnormalities in the mother regardless of whether the fetus has or does not have PKU. © Wiley‐Liss, Inc.
New syndrome involving the visual, auditory, respiratory, gastrointestinal, and renal systems
Authors: Siegler Richard L. , Brewer Eileen D. , Carey John C.
Published: June 2005

A previously undescribed fatal multisystem syndrome involving the eyes, ears, lungs, intestines, and kidneys occurred in sibs. They both presented during early childhood with cataracts, otitis media, intestinal malabsorption, chronic respiratory infection, and failure to thrive. Later, they developed recurrent pneumonia (one was shown to have immotile bronchial cilia) and progressive azotemia leading to end‐stage renal disease (ESRD) by late childhood. Both died of overwhelming infection (sepsis, meningitis). An autosomal recessive mode of inheritance is proposed since the normal parents were distant cousins, and 4 other sibs were normal. © Wiley‐Liss, Inc.
Biochemical characterization of a pedigree with mitochondrially inherited deafness
Authors: Prezant Toni Rita , Shohat Mordechai , Jaber Lutfi , Pressman Sheila , Fischel‐Ghodsian Nathan
Published: June 2005

A large kindred with a predicted 2‐locus inheritance of sensorineural deafness, caused by the combination of a mitochondrial and an autosomal recessive mutation, was examined at the biochemical level. Because of the mitochondrial inheritance of this disease, we looked for defects in the oxidative phosphory‐lation Complexes I, III, IV, and V, the 4 enzymes that include all of the 13 mitochondrially encoded polypeptides. Biosynthetic labelling of lymphoblastoid cells from deaf patients, unaffected siblings, and an unrelated control showed no difference in size, abundance, rate of synthesis, or chlo‐ramphenicol‐sensitivity of the mitochondrially encoded subunits. Since overall mitochondrial protein synthesis appears normal, these results suggest that the mitochondrial mutation is unlikely to be in a tRNA or rRNA gene. No change in enzymatic levels was seen in lymphoblastoid mitochondria of the deaf patients, compared to unaffected sibs and controls, for Complexes I and IV. Both affected and unaffected family members showed an increase in Complex III activity compared to controls, which may reflect the mitochondrial DNA shared by maternal relatives, or be due to other genetic differences. Complex V activity was increased in deaf individuals compared to their unaffected sibs. Since the family members share the presumptive mitochondrial mutation, differences between deaf and unaffected individuals likely reflect the nuclear background and suggest that the autosomal recessive mutation may be related to the increase in Complex V activity. These biochemical studies provide a guide for sequence analysis of the patients' mitochondrial DNA and for linkage studies in this kindred. © Wiley‐Liss, Inc.
Update on a family with hand–foot–genital syndrome: Hypospadias and urinary tract abnormalities in two boys from the fourth generation
Authors: Donnenfeld Alan E. , Schrager Deborah S. , Corson Stephen L.
Published: June 2005

We describe a fourth generation of involvement with hand–foot–genital syndrome. The first 3 generations of this family, which included 5 affected females and no affected males, were reported previously by Verp et al. [1983]. In the fourth generation, 2 affected males are identified. To our knowledge, the findings of bilateral vesicoureteral reflux in one boy and bilateral ureteropelvic junction obstruction in his cousin represent the first reports of urinary tract abnormalities in males with this syndrome.
Familial syndrome of endocrine and neuroectodermal abnormalities
Authors: Oerter Karen E. , Friedman Theodore C. , Anderson Hans C. , Cassorla Fernando G.
Published: June 2005

We report on a previously undescribed combination of endocrine and neuroectodermal abnormalities in four sibs from Burma. These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type II diabetes mellitus with elevated insulin levels, mild mental retardation, sensori‐neural deafness, and alopecia without pili torti. They also had a characteristic facial appearance and fleshy hands and feet. This family appears to have a previously undescribed combination of endocrine and neuroectodermal abnormalities. © Wiley‐Liss, Inc.
Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells
Authors: Bembi Bruno , Comelli Marina , Scaggiante Bruna , Pineschi Alberto , Rapelli Silvana , Gornati Rosalba , Montorfano Gigliola , Berra Bruno , Agosti Eriberto , Romeo Domenico
Published: June 2005

Five young patients with Niemann‐Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30–40% of the assays. © Wiley‐Liss, Inc.
Interstitial deletion of the short arm of chromosome 1 (46XY), del(1)(p13p22.3)
Authors: Mattia Frank R. , Wardinsky Terrance D. , Tuttle Deborah J. , Grix Arthur , Smith Kathleen A. , Walling Paula
Published: June 2005

A male patient with a de novo proximal interstitial deletion of the short arm of chromosome 1 (46XY), del(1)(p13p22.3) is described with multiple anomalies and developmental delay. This patient's clinical manifestations are compared to previously reported patients with deletions of chromosome 1p.© 1992 Wiley‐Liss, Inc.
Prenatal diagnosis of short rib (polydactyly) syndrome with situs inversus
Authors: de Sierra Teresa M. , Ashmead Graham , Bilenker Robert
Published: June 2005

We present a case of short rib (polydactyly) syndrome in which the diagnosis was made prenatally by ultrasound examination. The more specific diagnosis of short rib (polydactyly) syndrome type III was made on the basis of findings on radiographs obtained at birth. The sonographic and radiographic features are discussed. The patient had complete situs inversus and hypospadias. The former was reported in one other case of type III and the later has not been previously reported in this entity. © 1992 Wiley‐Liss, Inc.
Acrania: A manifestation of the Adams‐Oliver syndrome
Authors: Chitayat David , Meunier Catherine , Hodgkinson Kathy A. , Robb Laura , Azouz Michael
Published: June 2005

A 10‐year‐old male with acrania, distal limb anomalies, and abnormal arterial and venous cranial blood vessels is reported. Parental films and examination are normal. This case supports the hypothesis that acrania is a severe form of aplasia cutis congenita and is within the spectrum of Adams‐Oliver syndrome. It is proposed that the diagnosis of acrania requires assessment of both parents and proband to assess other manifestations of vascular disruption in order to provide accurate genetic counselling. © 1992 Wiley‐Liss, Inc.
New oral‐acral syndrome with partial agenesis of the maxillary bones
Authors: Verloes Alain , Koulischer Lucien
Published: June 2005

We report on a woman with congenital defect of the anterior part of the maxillary bone (including absence of incisors and canines) without cleft lip or palate, and ectrodactyly of the feet. This syndrome appears to represent a new entity of unknown cause. © 1992 Wiley‐Liss, Inc.
Characterization of an inversion duplication of the short arm of chromosome 8 by fluorescent in situ hybridization
Authors: Henderson Karen G. , Dill Fred J. , Wood Stephen
Published: June 2005

A de novo chromosome aberration in a woman with severe mental retardation and minor anomalies has been characterized cytogenetically. The patient's karyotype was described as 46, XX, inv dup (8)(p12 → p23.1). Previous Southern blot dosage studies with the marker locus D8S7 demonstrated that the patient was monosomic for this locus, suggesting that the rearrangement generated a duplication‐deficiency chromosome. We have reinvestigated this patient using fluorescent in situ hybridization with chromosome 8 cosmids and an Alu‐PCR product specific for 8p. These studies have confirmed directly that the duplicated chromosome also has undergone deletion. © 1992 Wiley‐Liss, Inc.
Child with multiple congenital anomalies and mosaicism 46, XX/46,XX, del (14)(q32.3)
Authors: Miller Bruce Alan , Jayakar Parul , Capó Hilda
Published: June 2005

We report on a female infant with multiple congenital anomalies and severe developmental delay in association with a rare, terminal deletion of chromosome 14 [karyotype:mosaic. 46,XX/46,XX del (14) (q32.3) = 36%:64%]. © 1992 Wiley‐Liss, Inc.
Oculo‐Auriculo‐Vertebral complex and uncommon associated anomalies: Report on 8 unrelated Brazilian patients
Authors: van Bever Yolande , van den Ende Jenny J. , Richieri‐Costa A.
Published: June 2005

We report on 8 Brazilian patients with the oculo‐auriculo‐vertebral (OAV) complex with associated uncommon anomalies of hydrocephalus, porencephalic cyst, hand abnormalities, terminal/paraxial hemimelia, Klippel‐Feil anomaly, Rokitansky sequence, fibrous dysplasia, and dextrocardia. Our patients show that in some instances a definite diagnosis can be difficult within the wide clinical picture of the OAV complex. © 1992 Wiley‐Liss, Inc.
Autosomal dominant insulin resistance syndrome due to a postbinding defect
Authors: Seemanová E. , Rüdiger H. W. , Dreyer M.
Published: June 2005

We investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and later overt insulin‐resistant diabetes mellitus (non‐insulin‐dependent diabetes mellitus, NIDDM). The patients have markedly curly scalp hair, deficient face and body hair. Their teeth were healthy and normal in size and position. The clinical and biochemical findings and characteristics of the insulin receptors investigated in fibroblasts are reported. There was normal insulin binding to fibroblasts in the 2 brothers and their father. However, insulin‐stimulated RNA synthesis was decreased as compared to that of normal control individuals. These findings suggest a postbinding defect of insulin action. The pedigree documents an autosomal dominant mode of inheritance. The diagnosis is of practical importance since it enables medical supervision of gene carriers in a pre‐clinical state of atherosclerotic complications and overt diabetes. The findings in this family have relevance also to the explanation of familial mild mental retardation and to the study of different forms of insulin resistance due to a disturbance in biosignal transfer. © 1992 Wiley‐Liss, Inc.
Congenital defects of the limbs and alcohol exposure in pregnancy: Data from a population based study
Authors: Froster Ursula G. , Baird Patricia A.
Published: June 2005

Limb deficiency may occur in offspring prenatally exposed to alcohol. In a study on limb deficiency occurring in 1,213,913 consecutive liveborn infants in British Columbia, born in the years 1952–1984, a total of 659 cases with limb deficiency was identified. Cases with documented maternal alcohol abuse in pregnancy in this group were analyzed separately. We found eight cases with severe prenatal alcohol exposure (6 F, 2 M). In six of the eight cases a terminal transverse defect of the forearm or hand was present. In the remaining two cases ulnar defects were identified. These observations give further support to the hypothesis that intrauterine alcohol exposure may cause limb defects. This has also been demonstrated in experimental animals. Terminal transverse defects made up a larger proportion of cases with known alcohol exposure (6/8) than of cases where alcohol exposure was not noted (217/651) (χ2 = 6.13; P < 0.025) in this study. The defects primarily involved the right hand and forearm. This suggests a vascular origin of the limb defects after intrauterine alcohol exposure. © 1992 Wiley‐Liss, Inc.
Delayed membranous cranial ossification in a mother and child
Authors: Angel Ariadna Gonzalez‐del , Carnevale Alessandra , Takenaga Raul
Published: June 2005

We report on a girl and her mother with delayed intramembranous ossification of the cranial vault. The 11‐month‐old girl had a large ossification defect involving parietal bones, squamous portion of temporal bones, and interparietal region of occipital bone, while the mother showed a complete ossified cranial vault with flat posterior parietal region and prominent occiput. Both had a similar face characterized by frontal bossing, hypertelorism, downward slant of palpebral fissures, flat nasal bridge, and short midface. On reviewing the literature, we concluded that these cases may be a dominant transmitted ossification defect with characteristic face, different from the cranium bifidum‐parietal foramina entity. © 1992 Wiley‐Liss, Inc.
Duplication (20p) in association with thyroid carcinoma
Authors: Clark P. , Jones K. L. , Freidenberg G. R.
Published: June 2005

We report on a girl with short stature, mental retardation, mutism, “coarse” facial appearance, and papillary‐follicular thyroid carcinoma. She had dup(20p) derived from a paternal balanced translocation [(12p;20p)]. We speculate that the carcinoma in our patient may be related to the deletion of material from 12p resulting in absence of genetic material normally required for the suppression of thyroid tumorigenesis. © 1993 Wiley‐Liss, Inc.
Apparent Greig cephalopolysyndactyly and sinus node disease
Authors: Fryns J. P. , De Waele P. , Van Der Hauwaert L. , Van Den Berghe H.
Published: June 2005

We present the clinical findings and follow‐up data from birth of 10.5 years in a boy with Greig cephalopolysyndactyly who, in addition, presents sinus node disease (“sick sinus syndrome”). The significance of the concurrence of Greig cephalopolysyndactyly syndrome, an autosomal dominant condition mapped at 7p13, and sinus node disease is discussed. © 1993 Wiley‐Liss, Inc.
Balanced complex rearrangement involving chromosomes 8, 9, and 12 in a normal mother, derivative chromosome 9 with recombinant chromosome 12 in her daughter with minor anomalies
Authors: Masuno Mitsuo , Asano Jun‐Ichi , Yasuda Kanji , Kondo Tomio , Orii Tadao
Published: June 2005

We report on a 19‐month‐old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,−9,−12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low‐set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be balanced. © 1993 Wiley‐Liss, Inc.
Cutaneous malignant melanoma and atypical moles associated with a constitutional rearrangement of chromosomes 5 and 9
Authors: Petty Elizabeth M. , Bolognia Jean L. , Bale Allen E. , Yang‐Feng Teresa
Published: June 2005

Hereditary cutaneous malignant melanoma (HCMM) with or without atypical moles has been described in several large kindreds worldwide. Despite numerous studies of these kindreds, the gene or genes responsible for this disorder has not yet been identified. Cytogenetic and molecular studies of melanoma tumor tissue and cell lines suggest that a gene involved in the pathogenesis of malignant melanoma lies on chromosome 9p. We describe a woman with atypical moles and multiple primary melanomas, who lacks a family history of HCMM, and, has a de novo constitutional unbalanced reciprocal translocation involving the short arms of chromosomes 5 and 9 with a cytogenetically visible deletion of 5p or 9p: [46,XX,‐5,‐9, +der(5)t(5;9) (p13.3 or 14.2;p13.3 or 21.2), +der(9)t(5;9)]. This finding supports the hypothesis that a gene predisposing to HCMM lies on the short arm of chromosome 9. © 1993 Wiley‐Liss, Inc.
In vitro chondrogenesis in human chondrodysplasias
Authors: Horton William A.
Published: June 2005

Bone morphogenesis depends on the sequential expression of multiple genes that first allow formation of mesenchymal anlagen, their replacement by cartilage models, and finally, the synthesis of new bone at growth plates. These processes require orchestration of synthesis of multiple collagens, proteoglycans and glycoproteins, the genes for many of which have been isolated and are being studied. Several genes carry mutations which are responsible for the chondrodysplasia phenotypes and can be studied at the gene level or by examining their expression in cultured chondrocytes.
Natural history of blue sclerae in osteogenesis imperfecta
Authors: Sillence D. , Butler B. , Latham M. , Barlow K.
Published: June 2005

Scleral hue is an important sign which distinguishes 2 broad groupings of patients, those with and those without blue sclerae with non‐lethal osteogenesis imperfecta (OI). Individuals with OI type I have distinctly blue sclerae which remain intensely blue throughout life. In OI type III and OI type IV the sclerae may also be blue at birth and during infancy, but the intensity fades with time such that these individuals have sclerae of normal hue by adolescence and adult life.
Non‐invasive prenatal diagnosis of osteogenesis imperfecta
Authors: Thompson Elizabeth M.
Published: June 2005

The main mode of non‐invasive prenatal diagnosis of osteogenesis imperfecta (OI) is fetal imaging, either by radiography or detailed ultrasonography. Radiography is more of historical interest and ultrasonography is in practice virtually exclusively used for non‐invasive second trimester diagnosis of OI. Both methods have also been reported later in pregnancy when diagnosis allows the most appropriate method of delivery to be planned. For example, a caesarean section can be avoided if the fetus is shown to have a form of OI associated with limited survival.

Ultrasonography is useful mainly for prenatal diagnosis of the severe forms of OI, especially the perinatally lethal forms (Sillence type II) and to a lesser extent for the severe progressively deforming forms (Sillence types III and III/IV). For the milder varieties of OI (Sillence types I and IV), many cases will be missed by scans. Invasive methods of prenatal diagnosis of OI (principally chorion villous sampling) are used for families with the milder dominant forms of OI and in severe forms of OI in which the actual biochemical or molecular defect in type I collagen is known.

Many cases of type II OI and a few of type III have now been reported which were detected by scans before 20 weeks gestation, the earliest being at 15 weeks, for type IIA OI. These include cases not only at genetic risk but also sporadic cases in which scans were done either routinely or for obstetric indications.

The ultrasonic abnormalities which are found include reduced echogenicity, multiple fractures, and deformity of the long bones, ribs and skull. There is a marked reduction of long bone length on measurement. The abnormalities are more severe in type II OI than in type III.

No false negative diagnoses have yet been reported for severe OI. Ultrasonography is a reliable mode of prenatal diagnosis for a pregnancy at risk of type II OI and probably also for type III, although more reports for the latter are needed to give more information about the likelihood of false negative diagnoses in this form of OI. For pregnancies at risk of types II and III OI, serial scans from 14 weeks gestation can be offered. An experienced operator, using a good realitime scanner should be able to detect type II OI by at least 17 weeks gestation, and type III OI by 19 to 20 weeks. In future, it may be possible to diagnose type II OI in the first trimester by ultrasound using an intravaginal transducer.
Somatic cell mosaicism: Another source of phenotypic heterogeneity in nuclear families with osteogenesis imperfecta
Authors: Constantinou‐Deltas C. D. , Ladda Roger L. , Prockop Darwin J.
Published: June 2005

Mutations in the genes coding for the proα1 and proα2 chains of type I procollagen have been found in many patients with osteogenesis imperfecta (OI), a heritable disorder of connective tissue. The severity of the disease varies between families and even among members of the same family. This phenotypic variability covers a spectrum extending from very mild forms that cannot be easily detected to perinatally lethal forms. One explanation for this phenotypic variability is the nature of the mutation in the type I procollagen genes. Another explanation is mosaicism. Here we report on 2 families with propositi who have OI, whereas their mothers had a milder form of the disease. In one family, the molecular defect was previously shown to be a substitution of α1904 by cysteine [Constantinou et al., 1990]. The biochemical phenotype was characterized by significant post‐translational over modification of the mutated type 1 collagen molecules which also had a 3–4°C decrease in their thermal unfolding. Also, secretion of the procollagen into the culture media was delayed. In the second family, the proposita's muscle fibroblasts synthesized and secreted type I procollagen molecules that were highly over‐modified along the entire length of their triple‐helical domain. Cells from the mother also synthesized normal and over‐modified protein, although the amount of over‐modified protein was less than that synthesized by her daughter's cells. The exact molecular defect has not yet been defined.

The simplest explanation for the phenotypic variability seen within these 2 families is that the mothers of the propositi are mosaic for their respective mutations so that not all of their somatic cells produce abnormal type I procollagen. Hence, one additional explanation for the phenotypic variability in OI is the abundance of the mutated allele or the degree of mosaicism in the patient's population of cells so that the first affected individual in a family may be mildly affected by a mutation which in a heterozygous form is potentially lethal in his or her offspring.
Barth syndrome: Clinical features and confirmation of gene localisation to distal Xq28
Authors: Adès L. C. , Gedeon A. K. , Wilson M. J. , Latham M. , Partington M. W. , Mulley J. C. , Nelson J. , Lui K. , Sillence D. O.
Published: June 2005

Barth syndrome is an X‐linked disorder characterised by cardioskeletal myopathy of variable severity usually fatal in childhood, and neutropenia. We ascertained a large pedigree with affected males in 3 generations. All affected males had dilated cardiomyopathy, with endocardial fibroelastosis (EFE) in some. The locus for Barth syndrome in this family was found to be closely linked to DXS52 (z = 2.78, θ = 0.0). The family was non‐recombinant for DXS52 in distal Xq28, but recombinant for DXS374 which maps proximal to DXS52. This localised Barth syndrome distal to DXS374, confirming a previous localisation to distal Xq28. As yet there is no evidence for genetic heterogeneity of Barth syndrome. © 1993 Wiley‐Liss, Inc.
Elevated human chorionic gonadotropin levels in pregnancies with sex chromosome abnormalities
Authors: Barnes‐Kedar I. , Amiel A. , Maor O. , Fejgin M.
Published: June 2005

Numerous reports have dealt with the usefulness of the maternal serum alpha‐fetoprotein marker (MsAFP) and human chorionic gonadotropin (MshCG) levels in the detection of Down syndrome (DS) and other autosomal trisomies. Only few reports have discussed the possible association of elevated levels of MshCG and sex chromosome aneuploidy. We wish to report on 3 cases in which this association was found. © 1993 Wiley‐Liss, Inc.
Segregation analysis of hypospadias: A reanalysis of published pedigree data
Authors: Harris Emily L. , Beaty Terri H.
Published: June 2005

Little is known about the cause of hypospadias, one of the most common urogenital anomalies in males. Familial clustering of hypospadias is well recognized, with heritability estimated to be about 70% under a simple multifactorial threshold model. Neither alternative genetic mechanisms nor shared environmental factors within families have been explored fully. To learn more about possible genetic mechanisms, we used 2 methods of segregation analysis to analyze a set of published family data.

These analyses are based on the families of 103 probands with hypospadias, who were ascertained through surgery departments in Denmark [Sørensen, 1953]. Urogenital examinations were performed on 95% (n = 1,510) of available male relatives, and 2.2% were found to have hypospadias. Within the probands' nuclear families, 12% of nonproband sons of normal fathers were affected. Using the mixed model of inheritance, both the autosomal dominant (AD) and codominant models fit these data better than either autosomal recessive (AR) or multifactorial models. Using the regressive logistic models, both AD and AR models were equally likely, and a model of nonMendelian sibship clustering gave a better fit to these data.

These inconsistent findings illustrate the difficulties commonly encountered in segregation analysis. Using 2 different statistical approaches, we found 2 different explanations, both of which differ from the autosomal recessive model originally suggested by Sørensen [1953]. Hypospadias in these families is almost certainly heterogeneous. Determining the cause of familial clustering of hypospadias will require careful delineation of persons with recognized syndromes from uncomplicated cases and detaied information on potential prenatal risk factors. © 1993 Wiley‐Liss, Inc.
Skeletal histopathology in fetuses with chondroectodermal dysplasia (Ellis‐van creveld syndrome)
Authors: Qureshi Faisal , Jacques Suzanne M. , Evans Mark I. , Johnson Mark P. , Isada Nelson B. , Samuel Yang S.
Published: June 2005

Chondroectodermal dysplasia (CED) is an uncommon autosomal recessive disorder and one of the short rib polydactyly syndromes (SRPS). It is characterized by acromelic and mesomelic shortness of limbs, postaxial polydactyly, small chest, ectodermal dysplasia, and in many cases, congenital heart defects. Controversy exists over possible changes in the growth plate. With the advent of ultrasonographic examination, increasing numbers of fetuses with osteochondrodysplasias are examined by pathologists. Since histopathologic examination of the skeletal system is useful in defining various osteochondrodysplasias and it has not been described in the fetus with CED, we herein describe 3 cases of fetal CED with emphasis on skeletal histopathology. All 3 pregnancies were terminated at 22–23 weeks because of ultrasonographic demonstration of short limbs and growth retardation. Radiologically, each fetus had acromelic and mesomelic shortness of long bones with smooth round metaphyses, vertically short iliac bones, short ribs and normal vertebrae. These findings are similar to those described in the larger newborn infant with CED. Histopathologically, the cartilage of the long bones showed chondrocytic disorganization in the physeal growth zone. The findings are dissimilar to those of larger infants and older children in whom chondrocytic columnization has been seen in the central physis and disorganization in peripheral physis. Furthermore, a variable degree of chondrocytic disorganization was also seen in the central physeal growth zone of vertebrae in these fetuses. Other findings noted at fetopsy were: polydactyly in all 3 cases, congenital heart defect in 2 and an abnormal frenulum in one case. The foregoing phenotypic and radiographic manifestations and skeletal histopathology help separate CED from other SRPS. © 1993 Wiley‐Liss, Inc.
Multiple epiphyseal dysplasia, Fairbank type: Morphologic and biochemical study of cartilage
Authors: Stanescu Ritta , Stanescu Victor , Muriel Marie‐Paule , Maroteaux Pierre
Published: June 2005

We have performed histochemical, immunohistochemical, electron microscopic, and bio‐chemical studies on the upper tibial cartilage from a case of multiple epiphyseal dysplasia, Fairbank type.

Most chondrocytes had intracytoplasmic inclusions which took the stains for proteins and were resistant to microbial collagenase digestion. The electron microscopic study showed that the inclusions are dilatations of the rough endoplasmic reticulum containing a material with alternately wide electron dense and electron lucent layers. Both in optical and in electron microscopy the inclusions fixed antibodies against the core protein of the large cartilage proteoglycans (aggrecans). They didn't stain with antibodies against type II collagen. The gel electrophoretic pattern of the large proteoglycans was different from normal controls.

The morphologic and biochemical alterations found in multiple epiphyseal dysplasia are similar to those already described in pseudoachondroplasia (Stanescu et al.: Eur J Pediatr 138:121–225, 1982; Stanescu et al.: J Bone Joint Surg 66A:817–836, 1984). However, the inclusions are smaller and the growth cartilage much less disorganized in multiple epiphyseal dysplasia.

The similarity of morphologic and biochemical abnormalities strongly suggests that the two diseases have a similar pathogenesis and belong to the same bone dysplasia family. © 1993 Wiley‐Liss, Inc.
New autosomal recessive lethal disorder with polycystic kidneys type Potter I, characteristic face, microcephaly, brachymelia, and congenital heart defects
Authors: Gillessen‐Kaesbach Gabriele , Meinecke P. , Garrett Christine , Padberg Barbara Christina , Rehder Helga , Passarge E.
Published: June 2005

We report on 3 pairs of sibs from unrelated families, who present with polycystic kidneys Potter type I claimed to be specific for the ARPKD, and with microbrachycephaly, hypertelorism with telecanthus, large posteriorly angulated fleshy ears and various congenital malformations including congenital heart defects. We suggest that they represent a previously unrecognized autosomal recessive lethal developmental disorder within the group of infantile polycystic kidney disease and Potter sequence. © 1993 Wiley‐Liss, Inc.
New epiphyseal stippling syndrome with osteoclastic hyperplasia
Authors: Shohat Mordechai , Rimoin David L. , Gruber Helen E. , Lachman Ralph
Published: June 2005

We present a lethal skeletal dysplasia characterized radiographically by severe stippling of the lower spine and long bones and periosteal cloaking. In contrast to the normal morphology of the epiphyses and growth plates, the marrow was filled with loose fibrous tissue containing numerous large multinucleated osteoclasts which were associated with Howship's lacunae on the endosteal surface. We suggest the term “;Pacman dysplasia”; to describe this unusual histologic change that characterizes this new bone dysplasia. © 1993 Wiley‐Liss, Inc.
In situ hybridization shows direct evidence of skewed X inactivation in one of monozygotic twin females manifesting Duchenne muscular dystrophy
Authors: Zneimer Susan M. , Schneider Nancy R. , Richards C. Sue
Published: June 2005

A novel combination of conventional and molecular cytogenetic techniques was used to investigate the expression of an X‐linked recessive disorder in one of monozygotic (MZ) twin females. These twins carry a deletion, approximately 300 kb in length, in one of their X chromosomes within the dystrophin gene, which is responsible for Duchenne muscular dystrophy (DMD) in one twin [Richards et al.: Am J Hum Genet 46:672–681, 1990]. A unique DNA fragment generated from an exon within this gene deletion was hybridized in situ to both twins' metaphase chromosomes, a probe which would presumably hybridize only to the normal X chromosome and not to the X chromosome carrying the gene deletion. Chromosomes were identified by reverse‐banding (R‐banding) and by the addition of 5‐bromodeoxyuridine (BrdU) in culture to distinguish early and late replicating X chromosomes, corresponding to active and inactive X chromosomes, respectively. Hybridization experiments showed predominant inactivation of the normal X chromosome in the twin with DMD. This is the first report showing direct evidence at the chromosome level of unequal inactivation of cytogenetically normal X chromosomes resulting in the manifestation of an X‐linked recessive disorder in one of monozygotic twin females. This study may now facilitate other research of unequal X inactivation and of females manifesting X‐linked recessive disorders. © 1993 Wiley‐Liss, Inc.
Complications in the genotypic molecular diagnosis of pseudo arylsulfatase A deficiency
Authors: Shen Ning , Li Zhen‐Guo , Waye John S. , Francis Gordon , Chang Patricia L.
Published: June 2005

Metachromatic leukodystrophy (MLD) is a severe neurodegenerative disease associated with deficient arylsulfatase A activity. Biochemical confirmation of this disorder has been complicated by a clinically normal but enzymatically deficient variant, pseudo arylsulfatase‐A deficiency (PD). The PD mutation is associated with two A→G transitions in the arylsulfatase A gene. They can be detected simultaneously with a recently developed 3′‐mismatch polymerase chain reaction, hence providing a rapid method for genotypic identification and resolving ambiguities of carrier identification based solely on enzyme analyses. However, we now report further genotypic complexities in the molecular diagnosis of PD due to the occurrence of another variant in which only one of the two A→G mutations of the PD allele was present. This variant confers reduced but readily detectable enzyme activity and behaves as a silent allele in the 3′‐mismatch polymerase chain reaction, thus leading to conflicting and erroneous genotype assignments in a family in which both variants and MLD co‐exist. The inconsistency was resolved after pedigree validation and further molecular analyses in which the two A→G mutations were assayed separately with allele‐specific oligonucleotides. Because arylsulfatase A analysis is one of the most commonly requested lysosomal enzyme assays and the PD mutant allele frequency is high in the general population, complexities as described in this family may be a recurrent problem that can be solved only with combined enzymatic and detailed molecular analyses. © 1993 Wiley‐Liss, Inc.
ADULT‐syndrome: An autosomal‐dominant disorder with pigment anomalies, ectrodactyly, nail dysplasia, and hypodontia
Authors: Propping Peter , Zerres Klaus
Published: June 2005

We describe a family with at least seven living persons who are affected by an hitherto undescribed autosomal‐dominant syndrome with variable expression, bearing close resemblance to the EEC syndrome and related disorders. The main manifestations are hypodontia and/or early loss of permanent teeth, ectrodactyly, obstruction of lacrimal ducts, onychodysplasia, and excessive freckling. We propose the acronym ADULT (acro‐der‐mato‐ungual‐lacrimal‐tooth)‐syndrome for this condition. © 1993 Wiley‐Liss, Inc.
New X‐linked syndrome with severe mental retardation, severely impaired vision, severe hearing defect, epileptic seizures, spasticity, restricted joint mobility, and early death
Authors: Gustavson Karl‐Henrik , Annerén Göran , Malmgren Helena , Dahl Niklas , Ljunggren Carl‐Gustaf , Bäckman Hans
Published: June 2005

A family with an X‐linked mental retardation syndrome involving seven children in two generations is reported. The syndrome includes microcephaly, severe mental retardation, optic atrophy with severely impaired vision or blindness, a severe hearing defect, spasticity, epileptic seizures, restricted movement of the large joints, and death in infancy or early childhood.

We conclude that this is a distinct, previously unrecognized X‐linked mental retardation syndrome. © 1993 Wiley‐Liss, Inc.