bluuebunny/crossref_metadata_2025 huggingface dataset:
Trisomy 2p: Analysis of unusual phenotypic findings
Authors: Lurie Iosif W. , Ilyina Helena G. , Gurevich Dora B. , Rumyantseva Natalja V. , Naumchik Irena V. , Castellan Claudio , Hoeller Adelheid , Schinzel Albert
Published: June 2005

We present three probands with partial trisomies 2p21–23 due to ins(4;2)(q21;p21p23) pat, 2p23‐pter due to t(2;4)(p23;q35)mat, and 2p21‐pter due to t(2;11)(p21;q23.3)mat. More than 50 cases of partial trisomy 2p have been reviewed and some abnormalities, unusual for most other types of structural autosomal imbalance, have been found in patients with inherited forms of 2p trisomy and in their non‐karyotyped sibs. Neural tube defects (anencephaly, occipital encephalocele, and spina bifida) were found in five probands and 4/6 affected non‐karyotyped sibs. The only triplicated segment common to all was 2p24. Different forms of “broncho‐pulmonary a/hypoplasia” (including two cases of lung agenesis) were described in four patients (overlapping triplicated segment was 2p21–p25). Three patients (with overlapping triplicated segment 2p23–p25) had diaphragmatic hernia. Abnormal rotation of the heart or L‐transposition of large vessels (with or without visceral heterotaxia) was found in two infants (overlapping triplicated segment 2p23p24). In two patients with common triplicated segment 2p22.3–p25, neuroblastoma has been described. The occurrence of all these defects may be explained either by the action of the same gene(s) mapped to 2p24 or by action of some independent factors located in different segments of the short arm. Although the latter hypothesis is much less probable, it can not be rejected at the present time. We propose the existence of a genetic system controlling surveillance of an abnormal embryo to explain the phenotypic differences between patients with the same imbalance within a family. In some “restrictive” combinations the abnormal embryos will die, although in “permissive” combinations they can survive. © 1995 Wiley‐Liss, Inc.
Synpolydactyly (type II syndactyly) with aplasia/hypoplasia of the middle phalanges of the toes: Report on a family with eight affected members in four generations
Authors: Camera Gianni , Camera Andrea , Pozzolo Silvano , Costa Margherita , Mantero Renzo
Published: June 2005

We describe a new family with synpolydactyly (syndactyly type II) with 8 affected members in 4 generations. Aplasia/hypoplasia of the middle phalanges of the toes was also noted. In our opinion, this anomaly represents a frequent manifestation of synpolydactyly. No other major skeletal or extraskeletal malformations were present. © 1995 Wiley‐Liss, Inc.
Presence of Y chromosome sequences and their effect on the phenotype of six patients with Y chromosome anomalies
Authors: Shankman S. , Spurdle A. B. , Morris D. , Rosendorff J. , Marques I. , Bernstein R. , Ramsay M.
Published: June 2005

The extent of Y chromosome material was determined in 6 southern African subjects with sex chromosome anomalies. Four of the subjects were phenotypically female, and 2 were phenotypically male. Molecular and cytogenetic findings were correlated with phenotypic expression. An X;Y translocation was found in both male subjects, and in one female subject. The remaining female subjects were characterized by an isodicentric Y, an isochromosome Yq, and a micromarker of undetermined origin, respectively. The individuals were tested for the presence of a number of Y‐specific DNA sequences. Molecular findings were generally compatible with the cytogenetic findings, and also with the phenotypic sex of the patients. All the female subjects had Y material and all but one were negative for the sex determining region of the Y (SRY). The somatic Ullrich‐Turner‐like findings present in 3 of the females were attributed to either the presence of a 45,X cell line and/or a single copy of Xp. The males both showed X;Y translocations without any detectable loss of Y DNA. Although molecularly very similar, the disparate clinical findings in these 2 subjects could have been accounted for by different X inactivation patterns. © 1995 Wiley‐Liss, Inc.
X‐linked α‐thalassemia/mental retardation (ATR‐X) syndrome: A new kindred with severe genital anomalies and mild hematologic expression
Authors: McPherson Elizabeth W. , Clemens Michele M. , Gibbons Richard J. , Higgs Douglas R.
Published: June 2005

We report a new kindred containing 4 patients with X‐linked α‐thalassemia/mental retardation syndrome ((ATR‐X). Like previously reported ATR‐X patients, these children are all genetic males with severe developmental delay and characteristic facial appearance. The genital anomalies are more severe than in most previous cases and have led to a female sex of rearing for 3 of the 4 patients. The hematologic expression is extremely mild and was not demonstrable on routine hematologic studies including hemoglobin electrophoresis, but the three living patients all had hemoglobin H inclusions on brilliant cresyl blue stained peripheral smears. The combination of skewed X‐inactivation and haplotype analysis at Xq12‐q21.3 confirmed carrier status in the 3 obligate carriers in the kindred and led to identification of an additional carrier. Two other women in the kindred appear to be noncarriers on the basis of normal X‐inactivation and/or inheritance of a different Xq12‐21.3 haplotype. More widespread use of brilliant cresyl blue staining for HbH inclusions in individuals with the facial phenotype of ATR‐X and/or ambiguous genitalia may lead to the identification of more affected patients and improved understanding of the clinical spectrum of ATR‐X. © 1995 Wiley‐Liss, Inc.
Duchenne muscular dystrophy and myotonic dystrophy in the same patient
Authors: Dubrovsky Alberto L. , Taratuto A. L. , Sevlever G. , Schultz M. , Pegoraro E. , Hoop R. C. , Hoffman E. P.
Published: June 2005

We report on the first patient identified with myotonic dystrophy and Duchenne muscular dystrophy (DMD). The family of the propositus had a strong history of myotonic dystrophy, and there was an intrafamilial pathological expansion of the responsible CTG repeat between the mildly affected mother (160 repeats; normal 27 repeats) and her more severely affected son (650 repeats), and his sister (650 repeats). The propositus was an isolated case of Duchenne muscular dystrophy with marked dystrophin deficiency in muscle biopsy. The patient was still ambulatory post age 16. Myotonic dystrophy could interfere to some extent with the progression of Duchenne dystrophy. However, other interpretations are possible. Twelve percent of dystrophin revertant fibers as observed by immunohistochemistry could be sufficient to ameliorate typical DMD clinical severity, or the patient may present a somatic mosaic. The pathophysiological interactions of these two unlinked disorders are discussed at the clinical and histopathological levels. © 1995 Wiley‐Liss, Inc.
Paracentric inversion X(q21.2q24) associated with mental retardation in males and normal ovarian function in females
Authors: Abeliovich Dvorah , Dagan Judith , Kimchi‐Sarfaty Chava , Zlotogora Joel
Published: June 2005

We describe a familial paracentric inversion (X)(q21.2 q24) in a family with 2 male and 2 female carriers. The males were mentally retarded and the females were normal with normal ovarian function. It is suggested that a recessive mental retardation (MR) gene was disrupted by one of the inversion breakpoints, although an X‐linked MR gene which by chance is linked to the inv(X) could not be ruled out. In the female carriers of the paracentric inversion a random X‐inactivation was demonstrated. The normal ovarian function is an exception to the concept of “critical region” at Xq13‐q26. © 1995 Wiley‐Liss, Inc.
Diabetic embryopathy: Possible pathogenesis
Authors: Sadler Laurie S. , Robinson Luther K. , Msall Michael E.
Published: June 2005

Despite recent emphasis upon improved metabolic control during early diabetic pregnancy, the offspring of insulin‐dependent diabetic women continue to have a 2‐ to 4‐fold increased risk of congenital malformations. We recently evaluated the affected offspring of 4 insulin‐dependent diabetic women. All had abnormal ears in association with vertebral defects. Our analysis of the structural defects of these infants and a review of the literature suggest that the pathogenesis of some cases of the diabetic embryopathy may involve a primary insult to developing somite mesoderm and associated cephalic neural crest cells. © 1995 Wiley‐Liss, Inc.
New syndrome of macrocephaly, hypertelorism, short limbs, hearing loss, and developmental delay
Authors: Bagatelle Rochelle , Cassidy Suzanne B.
Published: June 2005

We describe a boy with an apparently unique constellation of anomalies, including macrocephaly, short stature, relatively short limbs, hearing loss, developmental delay, sparse anterior scalp hair, hypertelorism, downslanting palpebral fissures, and a short nose with a broad, flat nasal bridge and anteverted nares. Chromosomes were normal and radiographs failed to show a bone dysplasia. We conclude that this represents a new syndrome. © 1995 Wiley‐Liss, Inc.
Pitt–Rogers–Danks syndrome: Further delineation
Authors: Lizcano‐Gil Luis A. , García‐Cruz Diana , García‐Cruz Olga , Sánchez‐Corona José
Published: June 2005

The Pitt–Rogers–Danks syndrome is an entity characterized by proportionate short stature and low weight of prenatal onset, moderate to severe mental retardation, seizures, and typical facial changes including microcephaly, telecanthus, upward or downward slanting palpebral fissures, prominent eyes, ocular abnormalities, hypoplastic maxilla, short philtrum, and large mouth. This is the seventh reported case, and the first one in which the patient also presents with optic atrophy. Autosomal recessive inheritance has been proposed until now, however, the increased paternal age seen in this case is suggestive of a possible autosomal dominant de novo mutation. © 1995 Wiley‐Liss, Inc.
De novo dup (5p) in a patient with congenital hypoplasia of the adrenal gland
Authors: Chen Harold , Hoffman William H. , Kusyk Christine J. , Tuck‐Muller Cathy M. , Hoffman Martin G. , Davis Loretta S.
Published: June 2005

We report on a black male child with congenital hypoplasia of the adrenal gland (CHA) with a de novo duplication of 5p [dir dup(5) (p13.3→p15.1)], confirmed by fluorescence in situ hybridization (FISH). In addition to a characteristic clinical course, the patient has hyperpigmentation (melanoderma) since birth, normal external genitalia, marked elevation of ACTH, and absent response to an IV ACTH challenge. To the best of our knowledge, this is the first case of congenital hypoplasia of the adrenal gland associated with a chromosome abnormality. Reviews of dup (5p) and of our patient suggest that duplication of 5p13.3‐pter has only minor phenotypic effect, while duplication of the relatively small critical segment p11‐p13.2 apparently causes far more deleterious changes. The concurrence of CHA and dup(5p) in our patient may indicate the possible gene localization of an autosomal form of CHA to either at or near 5p13.3 or 5p15.1. © 1995 Wiley‐Liss, Inc.
Mosaicism for a chromosome 8‐derived minute marker chromosome in a patient with manifestations of trisomy 8 mosaicism
Authors: Spinner Nancy B. , Grace Kim Rehberg , Owens Nancy L. , Sovinsky Lorraine , Pellegrino Joan E. , McDonald‐McGinn Donna , Zackai Elaine
Published: June 2005

We describe a patient with manifestations of the mosaic trisomy 8 syndrome and mo‐saicism for a minute marker chromosome. Fluorescence in situ hybridization (FISH) with a chromosome 8 probe confirmed that the marker was derived from chromosome 8. This is the smallest piece of chromosome 8 to be reported in a patient with mosaic trisomy 8 syndrome. When the clinical picture is strongly suggestive of trisomy for a specific chromosome region, we believe that FISH can be used to test markers in a guided, rather than random, fashion. © 1995 Wiley‐Liss, Inc.
Further delineation of the branchio‐oculo‐facial syndrome
Authors: Lin Angela E. , Gorlin Robert J. , Lurie Iosif W. , Brunner Han G. , van der Burgt Ineke , Naumchik Irena V. , Rumyantseva Natalja V. , Stengel‐Rutkowski Sabine , Rosenbaum Kenneth , Meinecke Peter , Muller Dietmar
Published: June 2005

We review 43 patients (15 new, 28 literature) with the branchio‐oculo‐facial (BOF) syndrome, which has a distinctive phenotype ranging from mild to severe forms, consisting of eye, ear, oral, and craniofacial anomalies. Virtually ubiquitous and possibly pathognomonic are the cervical/infra‐auricular skin defects. Much less common are supra‐auricular defects occurring as isolated anomalies or with cervical defects. Regardless of location, these lesions may have aplastic, “hemangiomatous,” or otherwise abnormal overlying skin, and draining sinus fistulae. Renal malformations are frequent, but congenital heart and central nervous system defects are rare. Psychomotor performance is usually normal, but development delays, hypotonia, and visual, hearing, and speech problems are common. Autoso‐mal dominant inheritance seems likely. Overlap between the BOF and branchio‐oto‐renal syndromes has been observed, but elucidation of its molecular basis is not yet available. This article also discusses 5 patients with atypical manifestations considered to be possibly affected or probably unaffected, who are sufficiently unusual to be excluded from the final data analysis. © 1995 Wiley‐Liss, Inc.
Interstitial deletion of 8q21→22 associated with minor anomalies, congenital heart defect, and Dandy‐Walker variant
Authors: Donahue Margaret L. , Ryan Rita M.
Published: June 2005

We describe an infant with a deletion of 8q21→22 who had distinct clinical manifestations including minor facial anomalies, a congenital heart defect, a Dandy‐Walker variant, and mild to moderate developmental delay. Her facial characteristics included small, wide‐spaced eyes, asymmetric bilateral epicanthal folds, a broad nasal bridge, a “carp‐shaped” mouth, micrognathia, and prominent, apparently low‐set ears. Three other reports describe children with larger proximal deletions of 8q that include 8q21 and q22. These four children all have similar facial appearance. Of the others reported, one had a congenital heart defect and one had craniosynostosis. This case, in addition to the previously noted three cases, helps in delineating a recognizable syndrome. © 1995 Wiley‐Liss, Inc.
Angelman syndrome: Validation of molecular cytogenetic analysis of chromosome 15q11‐q13 for deletion detection
Authors: White L. , Knoll J. H. M.
Published: June 2005

In a series of 18 individuals comprising parents of Angelman syndrome (AS) patients and AS patients with large deletions, mi‐crodeletions, and no deletions, we utilized fluorescence in situ hybridization (FISH) with genomic phage clones for loci D15S63 and GABRB3 for deletion detection of chromosome 15qll‐ql3. Utilization of probes at these loci allows detection of common large deletions and permits discrimination of less common small deletions. In all individuals the molecular cytogenetic data were concordant with the DNA deletion analyses. FISH provides an accurate method of deletion detection for chromosome 15qll‐ql3. © 1995 Wiley‐Liss, Inc.
Clinical profile of Angelman syndrome at different ages
Authors: Buntinx Inge M. , Hennekam Raoul C. M. , Brouwer Oebele F. , Stroink Hans , Beuten Joke , Mangelschots Kathelijne , Fryns J. P.
Published: June 2005

We describe 47 patients with Angelman syndrome (AS) from Belgium and the Netherlands, including the anamnestic data, the clinical and the behavioral attributes at different ages. The clinical picture of AS is most distinct between the ages of 2–16 years. Most patients of this age group show at least 8 of the major characteristics (bursts of laughter, happy disposition, hyperactive behaviour, microcephaly, brachycephaly, macrostomia, tongue protrusion, mandibular prognathism, widely spaced teeth, stiff and puppetlike movements, typical stature, wide based gait) beside the mental retardation and (almost) absence of speech, which is a universal trait. The diagnosis in infants is based on only a limited number of clinical characteristics or on anamnestic data. However, if these occur in combination, they are indicative of AS. In older patients, the diagnosis may be hampered in part because of the changing behavioral characteristics and the decreasing frequency of fits. Other manifestations, such as scoliosis, may become more pronounced with age. © 1995 Wiley‐Liss, Inc.
Developmental trends of sleep‐disordered breathing in Prader‐Willi syndrome: The role of obesity
Authors: Hertz Gila , Cataletto Mary , Feinsilver Steven H. , Angulo Moris
Published: June 2005

Polysomnographic recordings of 43 children and adults with Prader‐Willi syndrome (PWS) were inspected and classified into 5 age groups. The effect of age and body mass index (BMI) on measures of breathing, oxygen saturation, and sleep efficiency were analyzed. Body mass index (BMI) increased significantly between early childhood and preadolescent groups. Subjecting the data to analysis of variance showed an overall significant effect of BMI but no age effect on breathing parameters and oxygen saturation. Increased BMI was associated with decreased oxygen saturation and with higher apnea/hypopnea index. Sleep efficiency index was significantly lower in adults than in young children, preadolescent, and adolescent groups. These findings emphasize the role of obesity in the development of sleep‐related breathing abnormalities and nocturnal oxygen desaturation in patients with PWS. © 1995 Wiley‐Liss, Inc.
“C” Trigonocephaly syndrome: Report of a child with agenesis of the corpus callosum and tetralogy of Fallot, and review
Authors: Glickstein Julie , Karasik Jeffrey , Caride Diana Garcia , Marion Robert W.
Published: June 2005

We report on a new case of the Opitz “C” trigonocephaly syndrome. Our patient had agenesis of the corpus callosum, an anomaly seen only twice previously, and tetralogy of Fallot, described only once before. A review shows that a combination of conotruncal heart defects and midline brain anomalies characterizes patients with this entity. © 1995 Wiley‐Liss, Inc.
Trisomy 9 syndrome: Report of a case with Crohn disease and review of the literature
Authors: Wooldridge Jamie , Zunich Janice
Published: June 2005

We report on a 6‐year‐old boy with mosaic trisomy 9. The patient was born at 42 weeks of gestation to a 27‐year‐old G1 white woman. Birth weight was 2,820 g, length 52 cm, and Apgar scores were 4 and 6 at 1 and 5 min, respectively. The infant presented with apparently low‐set ears, overfolded helices, epicanthal folds, prominent nasal bridge, high‐arched palate, micrognathia, bilateral dislocated hips, left genu recurvatum, and cryptorchidism. Chromosome analysis showed an unusual karyotype: 47,XY,+inv(9qh+)/47,XY,+mar. The marker chromosome was thought to be a remnant of the inv(9qh+) chromosome. The mother's karyotype was 46,XX,inv(9qh+), while the father's was 46,XY.

At age 5 months, the patient developed seizures and gastroesophageal reflux. Crohn disease was diagnosed at age 2 years, although symptoms began at age 1 year. Recurrent bouts of pneumonia have occurred since the patient's birth. Severe psychomotor retardation was also noted.

Trisomy 9 syndrome was first reported in 1973. Over 30 cases have been reproted since then. Of these case reports, only 5 patients were older than 1 year. Inflammatory bowel disease has been reported in association with other chromosome abnormalities, but to our knowledge, has not been reported in trisomy 9 syndrome. © Wiley‐Liss, Inc.
Prenatal detection of the cholesterol biosynthetic defect in the Smith‐Lemli‐Opitz syndrome by the analysis of amniotic fluid sterols
Authors: Abuelo Dianne N. , Tint G. S. , Kelley Richard , Batta Ashok K. , Shefer Sarah , Salen Gerald
Published: June 2005

The Smith‐Lemli‐Opitz (SLO or RSH) syndrome is an autosomal recessive disorder characterized by a recognizable pattern of minor facial anomalies, congenital anomalies of many organs, failure to thrive, and mental retardation. Its cause is a defect in cholesterol biosynthesis characterized by abnormally low plasma cholestrol levels and concentrations of the cholestrol precursor 7‐dehydrocholesterol (7DHC) elevated up to several thousand‐fold above normal. We used capillary column gas‐chromatography to quantify sterols in amniotic fluid, amniotic cells, plasma, placenta, and breast milk from a heterozygous mother who had previously given birth to an affected son and in cord blood and plasma from her affected newborn daughter. The cholesterol concentration in amniotic fluid at 16 weeks gestation was normal, but 7DHC was 11% of total cholesterol, similar to cultured fibroblasts from patients with SLO syndrome. At 38 weeks, a girl with phenotype consistent with the syndrome was born. Cholesterol concentrations were abnormally low in cord blood and in the baby's plasma at 12 weeks, while levels of 7DHC were grossly elevated, confirming the prenatal diagnosis. The mother's plasma cholesterol increased steadily during gestation but remained below the lower 95% limit reported for normal control women. We conclude that it is now possible to detect the SLO syndrome at 16 weeks gestation by analyzing amniotic fluid sterols. © Wiley‐Liss, Inc.
Web neck anomaly and its association with congenital heart disease
Authors: Berdahl Laurie D. , Wenstrom Katharine D. , Hanson James W.
Published: June 2005

To investigate the relationship between congenital heart disease and jugular lymphatic obstruction as manifested in web neck anomaly, we used the Iowa Birth Defects Registry to determine the incidence of congenital heart defects (CHD) in infants with and without web neck.

Sixty percent of infants with web neck had CHD, with a high incidence of flowrelated defects such as hypoplastic left heart, coarctation, and secundum atrial septal defect. Sixty‐eight percent of infants with web neck had a genetic syndrome (37% Down syndrome, 13% Ullrich‐Turner syndrome, and 5% Noonan syndrome), and 24% had dysmorphic features consistent with lymphatic obstruction sequence. When infants with Down, Ullrich‐Turner, and Noonan syndrome and web neck were compared to infants with the same syndrome but without web neck, those with web neck were significantly more likely to have flow‐related heart defects. Infants with Ullrich‐Turner syndrome and web neck had an 11‐fold higher incidence of coarctation, compared to those with a normal neck.

Our data suggests web neck is associated with both flow and nonflow‐related heart defects. This association implies a pathogenetic relationship and appears to be independent of causal factors. The finding of web neck or nuchal cystic hygroma on a prenatal ultrasound or newborn examination should prompt a search for CHD. © Wiley‐Liss, Inc.
Autosomal‐recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome
Authors: Gross Anja , Kunze Jürgen , Maier Rolf F. , Stoltenburg‐Didinger Gisela , Grimmer Ingrid , Obladen Michael
Published: June 2005

We report on a macrosomic newborn girl with albinism, a black lock at the right temporo‐occipital region, and retinal depigmentation. Bilateral deafness was confirmed by brainstem auditory‐evoked potentials. In addition, the infant had a severe defect of intestinal innervation. Biopsy showed aganglionosis of the large intestine, and total absence of neurocytes and nerve fibers in the small intestine, indicating a total lack of sympathetic and parasympathetic innervation. The infant died of intestinal dysfunction at 5 weeks. She was the 14th child of consanguineous Kurdish parents. Four sibs of our patient had the same syndrome and died a few days after birth. The other 9 sibs are well, with an unremarkable phenotype. A syndrome of albinism, black lock, deafness, and a total lack of intestinal neural innervation has not yet been reported. It represents a new neural crest syndrome with autosomal‐recessive inheritance. © Wiley‐Liss, Inc.
Rapid in situ detection of chromosome 21 by PRINS technique
Authors: Pellestor Franck , Girardet Anne , Lefort Geneviève , Andréo Brigitte , Charlieu Jean P.
Published: June 2005

The “PRimed IN Situ labeling” (PRINS) method is an interesting alternative to in situ hybridization for chromosomal detection. In this procedure, chromosome labeling is performed by in situ annealing of specific oligonucleotide primers, followed by primer elongation by a Taq polymerase in the presence of labeled nucleotides. Using this process, we have developed a simple and semi‐automatic method for rapid in situ detection of human chromosome 21. The reaction was performed on a programmable temperature cycler, with a chromosome 21 specific oligonucleotide primer. Different samples of normal and trisomic lymphocytes and amniotic fluid cells were used for testing the method.

Specific labeling of chromosome 21 was obtained in both metaphases and inter‐phase nuclei in a 1 hour reaction. The use of oligonucleotide primer for in situ labeling overcomes the need for complex preparations of specific DNA probes. The present results demonstrate that PRINS may be a simple and reliable technique for rapidly detecting aneuploidies. © 1995 Wiley‐Liss, Inc.
Characterization of an unbalanced de novo rearrangement by microsatellite polymorphism typing and by fluorescent in situ hybridization
Authors: Zhao Jian , Gordon Patricia L. , Wilroy R. Sid , Martens Paula R. , Tarleton Jack , Shulman Lee P. , Simpson Joe Leigh , Elias Sherman , Tharapel Avirachan T.
Published: June 2005

Unbalanced de novo rearrangements, difficult to characterize by conventional cytogenetic techniques, may be elucidated by molecular approaches. By dinucleotide repeat polymorphism typing and fluorescence in situ hybridization (FISH), we have denned the composition of an unbalanced de novo translocation (46,XX,15p+) in a child with multiple congenital anomalies. Use of a microsatellite repeat D5S208 (localized to 5pl5) and polymerase chain reaction (PCR) analysis confirmed that the extra segment originated from the short arm of chromosome 5. Amplification of the patient's DNA with primers for dinucleotide repeats D5S350 and D5S118 showed that the entire 5p (from Spter to 5q11) was present in 3 copies. FISH confirmed the trisomic status of 5p, and further revealed the presence of centromeres of both chromosomes 5 and 15 on the rearranged chromosome thus delineating its dicentric nature. This information allowed us to redefine the de novo rearrangement in this patient as 46,XX,dic der(15)t(5;15)(q11;p11). © 1995 Wiley‐Liss, Inc.
Frontometaphyseal dysplasia: Neonatal radiographic diagnosis
Authors: Glass Ronald B. J. , Rosenbaum Kenneth N.
Published: June 2005

Frontometaphyseal dysplasia (FMD) is an uncommon genetic syndrome affecting bone and connective tissue. This condition is characterized by hyperostosis of the skull and prominence of the supraorbital ridges; long bones have flared metaphyses. Frontometaphyseal dysplasia is an X‐linked dominant trait with more severe manifestations in males and with extreme variability in females. Diagnosis in the neonatal period is difficult. We present 2 newborn boys with the radiographic findings of FMD. © 1995 Wiley‐Liss, Inc.
Craniosynostosis and kidney malformation in a case of Hennekam syndrome
Authors: Cormier‐Daire V. , Lyonnet S. , Lehnert A. , Martin D. , Salomon R. , Patey N. , Broyer M. , Ricour C. , Munnich A.
Published: June 2005

Hennekam syndrome is a rare autosomal recessive syndrome which was described for the first time in 1989. Here, we present a girl with intestinal lymphangiectasia, severe lymphedema of limbs, seizures, mild mental retardation, and facial anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she had an ectopic kidney and craniosynostosis of the coronal suture, 2 manifestations not previously reported in this syndrome. While the molecular basis of Hennekam syndrome remains, as yet, unknown, this report illustrates its variable clinical expression. © 1995 Wiley‐Liss, Inc.
Pigment variant of neuronal ceroid‐lipofuscinosis
Authors: Goebel Hans Hilmar , Gullotta Filippo , Bajanowski Thomas , Hansen Flemming Juul , Braak Heiko
Published: June 2005

A 6‐year‐old girl had progressive ataxia, and visual disturbances resulting in blindness. She died in her sleep at age 22 years. She shared with her sister and paternal relatives bilateral pes cavus deformities and impaired deep‐tendon reflexes which suggested Charcot‐Marie‐Tooth disease. Her sister, who also had both polyneuropathy and a progressive central nervous system (CNS) disease, did not have pigmentary retinopathy. At autopsy, the patient was found to have neuronal ceroid‐lipofuscinosis (NCL) marked by intraneuronal accumulation of autofluorescent granular lipopigments in ballooned perikarya and conspicuous extraneuronal pigmentation of subcortical grey matter, but without axonal spheroids. These findings indicate a pigment variant of NCL and represent one of very few patients recorded. The ultrastructure of the intraneuronal pigments was uniformly granular, while that of the extraneuronal pigments found within processes of the neuropil and glial perikarya was more variegated.

In addition to those patients with the pigment variant of NCL, described earlier by Jakob and Kolkmann [1973: Acta Neuropathol (Berl) 26:225–236], and Jervis and Pullarkat [1978: Neurology 28:500–503], our patient shared clinical symptoms with those described in a family afflicted with polyneuropathy and NCL by Wisniewski et al. [1987: J Child Neurol 2:33–41].

Currently, it is unclear whether these families harbor different genetic diseases or whether they have similar atypical forms of juvenile NCL (JNCL). We conclude that the spectrum of pigment variants in lysosomal diseases is heterogeneous: only few and recently described patients have had NCL, while others most likely had other forms of lipidosis. © 1995 Wiley‐Liss, Inc.
Late onset juvenile neuronal ceroid‐lipofuscinosis with granular osmiophilic deposits (GROD)
Authors: Hofman Irene L. , Taschner Peter E. M.
Published: June 2005

The juvenile‐onset subtype of the neuronal ceroid lipofuscinoses (JNCL) is well known [Hofman, ISBN90‐71534‐19‐7 1990] and ultrastructurally characterized by fingerprints and/or curvilinear bodies in many cell types. Linkage studies indicated a most likely location for CLN3, the gene involved in JNCL, in the interval between loci D16S297 and D16S57, within close proximity of the loci D16S298 and D16S299 [Mitchison et al., Genomics 22:465–468, 1993].

We present two sibs with a late onset progressive disease of mental deterioration, progressive macular degeneration, motor disturbances, and epilepsy. Histological symptoms of neuronal ceroid lipofuscinosis and ultrastructural granular osmiophilic deposits (GROD) in lymphocytes and neurons are found. Individual haplotypes at polymorphic marker loci on chromosome 16 were constructed to determine whether JNCL with GROD is linked to the CLN3 locus. © 1995 Wiley‐Liss, Inc.
Tissue and cellular distribution of subunit c of ATP synthase in Batten disease (neuronal ceroid‐lipofuscinosis)
Authors: Rowan Sarah A. , Lake B. D.
Published: June 2005

The major protein component of the storage bodies in the late infantile (LIB) and juvenile (JB) forms of Batten disease is subunit c of ATP synthase (subunit c). Ultrastructurally the stored material may appear as curvilinear bodies, fingerprint profiles, or a mixture of both, dependent upon the form of Batten disease and the cell type. The mnd/mnd mouse, an animal model for Batten disease, also stores subunit c and has loosely stacked lamellae within the neurons of the brain and in other cells and tissues. Using a range of tissue samples, immunolocalization, using avidin‐biotin techniques at the LM level and postembedding immunogold‐labelling (5 nm) with silver enhancement at the EM level, were used to investigate specific subunit c immunoreactivity. Subunit c storage was displayed in a number of cells, including neurons, muscle cells, adipocytes, macrophages, endothelial and some epithelial cells, and exocrine and endocrine cells. By EM, subunit c was localized to all curvilinear‐type storage bodies, but to nowhere else within the cell. It was not present over fingerprint profiles, the characteristic storage pattern of neurons within the JB gut, possibly due to steric factors. Preliminary studies in the mnd mouse showed subunit c immunoreactivity localized to storage profiles seen ultrastructurally in neurons of the brain, and liver and heart cells. We suggest that accumulation and distribution of subunit c within a variety of cell types, and its consistent absence in others, may be related to the particular cell type's longevity and its metabolic demand. © 1995 Wiley‐Liss, Inc.
Cellular distribution of lesions in Batten disease
Authors: Chronister Robert , Dyken Paul , Fields Phillip A. , Maertens Paul
Published: June 2005

One of the characteristic manifestations of chronic neuronal lipofuscinosis (Batten disease) is a marked predisposition for epileptic seizures. The management of these seizures is very difficult. The present study was initiated to determine what mechanisms could account for the seizure disorder. Tissue was examined from a patient with a history of Batten disease that was histologically verified. Reduced silver and Golgi impregnations were done on the parietal cortex of the patient. There was no evidence of the marked dendritic abnormalities seen in classic epileptic foci. Instead there was marked swelling and dilatation of the axon hillock and initial segment. This finding suggested that inhibition of these pyramidal neurons was markedly attenuated due to disruption of initial segment inhibitory synapses. Studies are continuing to determine if the GABA decreases seen in Batten disease may in part be due to trophic sequences brought about by loss of these critical inhibitory synapses. © 1995 Wiley‐Liss, Inc.
Decreasing hydraulic conductivity of Bruch's membrane: Relevance to photoreceptor survival and lipofuscinoses
Authors: Starita Carla , Hussain Ali A. , Marshall John
Published: June 2005

Deterioration of visual performance leading to blindness is particularly severe in the early‐onset forms of Batten disease. Metabolic support of the neural retina is critically dependent on the choroidal blood supply and on efficient transport pathways through Bruch's membrane and the retinal pigment epithelium (RPE). Conversely, degradation products and, in particular, damaged membranous components of photoreceptor outer segments must be removed in the opposite direction. Incomplete breakdown of damaged “spent” discs leads to the age‐related accumulation of lipofuscin‐like pigments in the RPE, and these in turn influence the degenerative changes in Bruch's membrane. The generalized and extensive deposition of lipofuscin‐like material in Batten disease is therefore likely to exacerbate the degenerative changes in Bruch's membrane, and thereby compromise local fluid dynamics. The hydrodynamic properties of Bruch's membrane were examined in normal donor eyes and showed a precipitous decline of hydraulic conductivity during early life. In fact, the maximal capacity for fluid transport was halved for every 17 years of life. This finding is therefore highly relevant to the development of ensuing pathology in the neuronal ceroid‐lipofuscinoses. © 1995 Wiley‐Liss, Inc.
Sphingolipid activator proteins (SAPS) are stored together with glycosphingolipids in the infantile neuronal ceroid‐lipofuscinosis (INCL)
Authors: Tyynelä Jaana , Baumann Marc , Henseler Margarete , Sandhoff Konrad , Haltia Matti
Published: June 2005

The storage material isolated from the brains of patients with infantile neuronal ceroid‐lipofuscinosis (INCL) contains, on average, 43% protein and 35% lipids on a dry weight basis. Recently we identified the major storage proteins as sphingolipid activator proteins (SAPs) A and D by direct sequencing. In the present study we used monospecific anti‐sap‐B‐, anti‐sap‐C, and anti‐sap‐D‐antisera in immunohistochemical and Western analyses to show that sap‐D is, indeed, an integral component of the storage bodies. In contrast, no (or little) immunoreactivity for sap‐B or sap‐C was detected in the INCL storage granules. This observation is of interest for an understanding of the pathogenesis because the four SAPs are produced from a single precursor protein by proteolytic cleavage.

Furthermore, we analysed the stored lipids on high performance thin layer chromatography combined with different staining techniques. In this preliminary analysis we found two glycosphingolipids, yet to be identified, to be common for all INCL patients. © 1995 Wiley‐Liss, Inc.
Genome‐wide search for CLN2, the gene causing late‐infantile neuronal ceroid‐lipofuscinosis (LNCL)
Authors: Haines J. L. , Boustany R.‐M. N. , Worster T. , Ter‐Minassian M. , Jondro P. , Lerner T. J.
Published: June 2005

The loci for the juvenile (CLN3) and infantile (CLN1) neuronal ceroid lipofuscinosis (NCL) types have been mapped by genetic linkage analysis to chromosome arms 16p and 1p, respectively. The late‐infantile defect CLN2 has not yet been mapped, although linkage analysis with tightly linked markers excludes it from both the JNCL and INCL loci. We have initiated a genome‐wide search for the LNCL gene, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 US families and 11 Costa Rican families. To date, we have completed typing with over 50 markers on chromosomes 2, 9, 13, and 18–22. The results of this analysis formally exclude about 10% of the human genome as the location of the LNCL gene. © 1995 Wiley‐Liss, Inc.
Michels syndrome in a Brazilian girl born to consanguineous parents
Authors: Guion‐Almeida M. L. , Rodini E. S. O.
Published: June 2005

We report on a Brazilian girl born to consanguineous parents and presenting with craniosynostosis, telecanthus, blepharophi‐mosis, blepharoptosis, epicanthus inversus, cleft lip and palate, skeletal defects, and hearing loss. This combination of anomalies appears to constitute the Michels syndrome. © 1995 Wiley‐Liss, Inc.
Nonspecific X‐linked mental retardation with macrocephaly and obesity: A further family
Authors: Baraitser M. , Reardon W. , Vijeratnam S.
Published: June 2005

The phenotypic nonspecificity of many forms of X‐linked mental retardation has hampered attempts to classify them into clinically homogeneous groups. One such condition, described by Clark and Baraitser [1987: Am J Med Genet 26:13–15], has been the subject of a single pedigree report to date. We now describe a further pedigree whose affected members share many manifestations with those reported by Clark and Baraitser, and we consider the possible distinction between this condition and Atkin‐Flaitz syndrome. © 1995 Wiley‐Liss, Inc.
Tel Aviv–Heidelberg three‐generation offspring study: Genetic determinants of apolipoprotein A1 and apolipoprotein B
Authors: Livshits G. , Blettner M. , Graff E. , Hoting I. , Wahrendorf J. , Brunner D. , Schettler G.
Published: June 2005

The contribution of major gene and multi‐factorial effects on variation of plasma apolipoproteins Al and B has been tested in a large sample of population‐based Israeli pedigrees. Our most parsimonious and best fitting model for both apolipoproteins is consistent with Mendelian transmissibility, with significant contribution of major genes (with 2 alleles recessive and dominant within each locus) and polygenes, but neglects effects of common sib environment as well as related intergeneration differences in polygenic effects. Total genetic effects explain 71 and 58% of phenotypic variance of APO‐A1 and APO‐B levels. The major genes account for about 44 and 32% of the variance in APO‐A1 and APO‐B, respectively, and the frequency of the recessive alleles determining the high level of apolipoproteins under the study in the Israeli population is in the vicinity of 40% at each locus. © 1995 Wiley‐Liss, Inc.
Follow‐up study in a patient with Setleis syndrome
Authors: Tsukahara Masato , Okabe Takahiro , Ohtsuka Morimasa , Furukawa Susumu
Published: June 2005

We report on an 8‐year‐old Japanese boy with Setleis syndrome. The patient had a very characteristic “coarse” facial appearance, bitemporal “forceps marks,” skin aplasia, sparse hair, and skin hypo‐ and hy‐perpigmentation. He also had previously undescribed manifestations, including an aberrant hair pattern of the forehead, linear skin lesions on the forehead, short palpebral fissures, a small skin tag on the right cheek, cone‐shaped teeth, and pectus carinatum. Dermatoglyphic studies documented aberrant distal palmar creases (simian crease variant), 8 arches, and reduced total finger ridge count. When serial photographs were reviewed, his facial characteristics became more obvious with increasing age. © 1995 Wiley‐Liss, Inc.
F‐syndrome (F‐form of acro‐pectoro‐vertebral dysplasia): Report on a second family
Authors: Camera Gianni , Camera Andrea , Pozzolo Silvano , Costa Margherita , Mantero Renzo
Published: June 2005

We report on a father and daughter in the second known family affected with F‐syn‐drome. The first family, with 8 affected members, was reported by Grosse et al. [1969: BD:OAS V (3):48–63]. F‐syndrome, an autoso‐mal‐dominant trait, is mainly characterized by acral defects that may also involve the sternum and the lumbosacral spine. Synostoses between capitate and hamate, and between talus and navicular, are invariably present; other carpal and tarsal bones are sometimes incorporated into the fusion. The hand malformation is principally a malformation of the first 2 rays. In our patients, the short and malformed thumb was webbed with the index finger, which was radially deviated with duplication of the middle and distal phalanges. In the feet, polydactyly and severe metatarsal and toe anomalies were present. The father had a prominent sternum with pectus excavatum, whereas the daughter had no sternal deformity. Both of them had a mild failure of fusion of posterior arch L5 and/Or Si. © 1995 Wiley‐Liss, Inc.
Multiple herniae: A defect in the celomic mesoderm?
Authors: Zaglul Horacio F. , Odita John C.
Published: June 2005

We report on a child with congenital bilateral cervical lung herniation with associated retrosternal (Morgagni), posterolateral (Bochdalek), esophageal hiatal, and inguinal herniae, and with multiple urinary bladder diverticuli. These multiple herniations may be secondary to a defect in the embryonic celomic mesoderm. © 1995 Wiley‐Liss, Inc.
Distinct skeletal abnormalities in four girls with Shprintzen‐Goldberg syndrome
Authors: Adés Lesley C. , Morris Lloyd L. , Power Rick G. , Wilson Meredith , Haan Eric A. , Bateman John F. , Milewicz Dianna M. , Sillence David O.
Published: June 2005

We describe 4 girls with Shprintzen‐Goldberg syndrome. Skeletal abnormalities common to 3 of them include bowing of long bones (with a variable degree of progression over time), flare of the metaphyses, a large anterior fontanel with persistent patency into the second to fourth years of life, 13 pairs of ribs, distinct vertebral abnormalities which were absent neonatally but evolved by the second year of life, and progressive osteopenia. These abnormalities were generalized and, in one case, progressive over the first few years of life. Communicating hydrocephalus was present in all 4 cases. The eldest, an 11‐year‐old girl, had additional anomalies not reported previously in this syndrome, including intestinal malrotation, an anteriorly placed anus, and mild cerebral atrophy. This is the first detailed report of skeletal manifestations in this rare disorder of unknown cause. These cases, in conjunction with a review of the literature, suggest that skeletal abnormalities are common in Shprintzen‐Goldberg syndrome. © 1995 Wiley‐Liss, Inc.
Mutations in PAX3 that cause Waardenburg syndrome type I: Ten new mutations and review of the literature
Authors: Baldwin Clinton T. , Hoth Christopher F. , Macina Roberto A. , Milunsky Aubrey
Published: June 2005

Waardenburg syndrome (WS) is an autosomal‐dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, and pigmentary disturbances, and it represents the most common form of inherited deafness in infants. WS type I is characterized by the presence of dystopia canthorum, while individuals with WS type II have normally‐located canthi. WS type III is similar to WS type I but is also characterized by musculoskeletal abnormalities. Defects in the PAX3 gene, a transcription factor expressed during embryonic development, have been shown to cause WS types I and III in several families. In contrast, mutations in PAX3 do not cause WS type II, and linkage of the disease to other chromosomal regions has been demonstrated. We describe 10 additional mutations in the PAX3 gene in families with WS type I. Eight of these mutations are in the region of PAX3, where only one mutation has been previously described. These mutations, together with those previously reported, cover essentially the entire PAX3 gene and represent a wide spectrum of mutations that can cause WS type I. Thus far, all but one of the mutations are private; only one mutation has been reported in two apparently unrelated families. Our analysis thus far demonstrates little correlation between genotype and phenotype; deletions of the entire PAX3 gene result in phenotypes indistinguishable from those associated with single‐base substitutions in the paired domain or homeodomain of PAX3. Moreover, two similar mutations in close proximity can result in significantly different phenotypes, WS type I in one family and WS type III in another. © 1995 Wiley‐Liss, Inc.
Acute intermittent porphyria: A single‐base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide
Authors: Lee Grace Y. , Astrin Kenneth H. , Desnick Robert J.
Published: June 2005

Acute intermittent porphyria (AIP) is an autosomal‐dominant inborn error of metabolism that results from the half‐normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB‐synthase). AIP is an ecogenetic condition, since the life‐threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB‐synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solidphase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. © 1995 Wiley‐Liss, Inc.
Geleophysic dysplasia: A report of three affected boys—prenatal ultrasound does not detect recurrence
Authors: Rosser Elisabeth M. , Wilkinson Andrew R. , Hurst Jane A. , McGaughran Julie M. , Donnai Dian
Published: June 2005

Geleophysic dysplasia is characterized by short stature with short limbs and brachydactyly, a “happy” facial appearance, and joint contractures. Infiltration of heart valves and liver with a mucopolysaccharide‐like substance has been demonstrated in some patients. A metabolic pathogenesis is suspected, but has not yet been identified. We report on 3 boys with the condition, 2 of whom are brothers. Serial ultrasound scans were performed on 2 of the cases during pregnancy, but short limbs did not become obvious until after 28 weeks of gestation, making it an uninformative procedure for prenatal diagnosis. © 1995 Wiley‐Liss, Inc.