bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordance of muscular dystrophy in monozygotic female twins: Evidence supporting asymmetric splitting of the inner cell mass in a manifesting carrier of Duchenne dystrophy
Authors: Lupski James R. , Garcia Carlos A. , Zoghbi Huda Y. , Hoffman Eric P. , Fenwick Raymond G.
Published: June 2005

In 1990, Richards et al. reported dramatically skewed lyonization in a set of female monozygotic twins heterozygous for Duchenne muscular dystrophy (DMD). The skewed inactivation pattern was symmetrical in opposite directions, one twin being affected with DMD, the other one being normal. Here, we report an additional set of female monozygotic twins heterozygous for a mutation at the dystrophin locus. Similarly, one shows a manifesting carrier phenotype while one is normal. However, unlike the previous report, we find a skewed X inactivation pattern only in the affected twin, while the normal twin showed a random X inactivation pattern. Our results lend considerable experimental support for the models of twinning and X inactivation recently outlined by Nance in 1990, in that these twins probably represent asymmetric splitting of the inner cell mass (ICM): The affected twin likely arose when a small proportion of the ICM split off after lyonization had occurred. In this situation, the original ICM could give rise to the normal twin with random lyonization, while the newly split cells would experience catch‐up growth and lead to the affected twin. Genetic studies of this family showed that the specific dystrophin gene mutation was an exon duplication that arose sporadically in the paternally derived X chromosome.
Non‐random association between DNA markers and Huntington disease locus in the Italian population
Authors: Novelletto Andrea , Mandich Paola , Bellone Emilia , Malaspina Patrizia , Vivona Giuseppa , Ajmar Franco , Frontali Marina
Published: June 2005

A group of Huntington disease (HD) families of Italian ancestry was analyzed for 11 RFLPs from genetic loci mapped in 4p16 and genetically linked to the HD gene. We found a statistically significant difference of allele distributions in HD vs normal chromosomes for loci D4S10, D4S127, and D4S43. This observation increases the number of loci in linkage disequilibrium with HD. However, the amount of disequilibrium does not allow either a finer localization of the HD gene or a substantial improvement in risk calculations.
DNA analysis in patients with lissencephaly type I and other cortical dysplasias
Authors: Oostra B. A. , de Rijk‐van Andel J. F. , Eussen H. J. , van Hemel J. O. , Halley D. J. J. , Niermeijer M. F.
Published: June 2005

DNA markers YNZ22.1, YNH37.3, 144D6, and VAW508 were studied in five patients with the Miller‐Dieker syndrome, 17 patients with the isolated lissencephaly sequence, one patient with a non‐classified lissencephaly, and nine patients with an atypical cortical dysplasia. All patients had normal chromosomes except for a deletion 17p13.3 in one of the five Miller‐Dieker patients. The five Miller‐Dieker patients showed deletions of markers YNZ22.1 and YNH37.3 in contrast to the other patients tested. In one patient, the deletion was in the maternally contributed chromosome. Prenatal diagnosis by DNA analysis allowed exclusion of the recurrence of Miller‐Dieker syndrome in a subsequent pregnancy.
Presymptomatic testing for adult onset polycystic kidney disease in at‐risk kidney transplant donors
Authors: Hannig Vickie L. , Hopkins Jeanne R. , Johnson H. Keith , Phillips John A. , Reeders Stephen T.
Published: June 2005

Autosomal dominant adult‐onset polycystic kidney disease (ADPKD) is estimated to have an incidence of 1/1,000 and accounts for approximately 10% of all end‐stage renal disease in the United States. While relatives are attractive as renal donors due to their availability and the improved transplant success associated with living‐related donors, they may coincidentally be at risk for ADPKD. Accurate presymptomatic testing for at‐risk potential donors is critical for both the donor and the recipient. We report here 2 families in which presymptomatic testing for ADPKD was accomplished by DNA linkage analysis on several potential renal donors prior to transplant. This resulted in the protection of both donors and recipients by preventing the transplantation of a kidney affected by ADPKD. Thorough counseling prior to DNA analysis (including discussion of accuracy and possible testing outcomes of presymptomatic diagnosis of ADPKD, diagnosis of noncarrier status, false paternity, and noninformative study) was essential to provide informed consent and preserve confidentiality within the family. Confidentiality for potential donors found presymptomatically to be affected (with a 94% or greater probability) was especially difficult to maintain.
Severe anomalies associated with ring chromosome 7
Authors: Biesecker Leslie G. , Cox Beth , Glover Thomas W.
Published: June 2005

A newborn infant with the polyasplenia sequence, intrauterine growth retardation, cutaneous nevi, and minor anomalies was found to have mosaicism for ring chromosome 7. This patient's anomalies are markedly different from those of previous patients reported with this cytogenetic anomaly.
Uniparental disomy, isodisomy, and imprinting: Probable effects in man and strategies for their detection
Authors: Engel Eric , DeLozier‐Blanchet C. Dawn
Published: June 2005

The concept of uniparental disomy—the presence of a chromosome pair derived solely from one parent in a diploid offspring—was introduced in 1980 as a probable consequence of the high rate of germ cell aneuploidy in man, and has now been convincingly demonstrated through molecular analyses in several families. A most likely mechanism for the production of uniparental disomy is the chance reunion, and complementation, of 2 gametes aneuploid for the same chromosome member; uniparental disomy could also occur through other mechanisms including postzygotic nonsegregation in a trisomic conceptus.

Uniparental dlsomy may result in isodisomy, i.e., homozygosity of a series of contiguous alleles in a pair of homologues. The presence and degree of isodisomy in an offspring depend in turn on the occurrence, timing, and extent of the meiotic recombination that had occurred in the chromosome pair of the disomic gamete involved.

Uniparental disomy with or without isodisomy can explain a number of unusual observations, such as the unexpected pattern of transmission of a genetic disorder. The two may be associated with an imprinting effect to produce pathological phenotypes, as has been observed in the mouse, and may be the basis for a number of syndromes of as yet unclear cause.

The evidence for uniparental disomy, isodisomy, and imprinting in man is reviewed, and strategies for their detection presented.
Linkage of an Alzheimer disease susceptibility locus to markers on human chromosome 21
Authors: Heston Leonard L. , Orr Harry T. , Rich Stephen S. , White June A.
Published: June 2005

We assessed linkage between Alzheimer disease (AD) and restriction fragment length polymorphisms (RFLPs) from human chromosome 21 in 8 families selected because of multiple occurrences of AD and large size. Sib‐pair analysis demonstrated significant evidence for linkage between 2 markers (D21S1 and D21S11) and disease. Two markers, D21S13 and D21S52, did not yield evidence in favor of linkage to disease and a 5th, D21S16, was uninformative. The results confirm that a susceptibility locus for Alzheimer disease is located on chromosome 21. In contrast to other investigators who demonstrated linkage between AD and chromosome 21 loci, we found evidence in favor of linkage in both late‐ (greater than age 65) and earlyonset families.
Smith‐Fineman‐Myers syndrome in two brothers
Authors: Adès Lesley C. , Kerr Bronwyn , Turner Gillian , Wise Grahame
Published: June 2005

We report on 2 brothers with a distinctive facial appearance, severe mental retardation, short stature, cryptorchidism, asplenia in one, dramatic failure to thrive, early hypotonia, and later hypertonia all suggestive of the Smith‐Fineman‐Myers syndrome. All 5 of the reported cases have been males, suggesting X‐linked inheritance.
Retrospective survey of urea cycle disorders: Part 2. Neurological outcome in forty‐nine Japanese patients with urea cycle enzymopathies
Authors: Nagata N. , Matsuda I. , Matsuura T. , Oyanagi K. , Tada K. , Narisawa K. , Kitagawa T. , Sakiyama T. , Yamashita F. , Yoshino M.
Published: June 2005

We analyzed neurological data, including DQ or IQ, EEG, and CT scan, in 49 patients with urea cycle enzymopathies, all of whom were included in a retrospective survey from 1978–1988 in Japan. We classified 3 groups depending on age‐at‐onset: group 1 (0–28 days, N = 11), group 2 (29 days‐5 years, N = 31), and group 3 (>5 years, N = 7). The least DQ or IQ score and the highest CT score, representing the most severe brain damage was found in group 1, and the highest DQ or IQ and the least CT score was found in group 3. Intermediate scores of both parameters were found in group 2. There was a negative correlation between these 2 parameters (r = ‐ 0.82, P < 0.01). Abnormal EEG during the attack‐free period was predominantly observed in patients with CT abnormalities compared to those with a normal CT scan (P < 0.01). Approximately 40% of the patients, mostly in groups 2 and 3 (92.8%) had normal findings in all 3 parameters. Thus, the magnitude of developmental abnormalities is clearly related to the degree of brain damage and to the age‐at‐onset of these diseases.
Autosomal dominant transmission of congenital erythroid hypoplastic anemia with radial abnormalities
Authors: Hurst J. A. , Baraitser M. , Wonke B.
Published: June 2005

We describe a mother and son with congenital hypoplastic anemia. The mother has apparently normal thumbs and forearms but her son has bilateral radial hypoplasia. They provide a further example of dominant inheritance of Diamond‐Blackfan anemia/Aase syndrome and suggest that thumb and radial abnormalities are a component of this syndrome.
“Snail‐like pelvis” chondrodysplasia: A further case report
Authors: Camera G. , Scarano G. , Tronci A. , La Cava G. , Mastroiacovo P.
Published: June 2005

Chondrodysplasia with snail‐like pelvis (Schnechenbecken dysplasia) is a rare distinct, lethal, short‐limbed dwarfism. We describe the clinical and radiological features of a new case in an Italian family.
MASA syndrome: Clinical variability and linkage analysis
Authors: Rietschel M. , Friedl W. , Uhlhaas S. , Neugebauer M. , Heimann D. , Zerres K.
Published: June 2005

We report on a family with three males with MASA syndrome (mental retardation, aphasia, shuffling gait, and adducted thumbs). One patient demonstrated spastic paraplegia and psychomotor retardation but no adducted thumbs. The described family underlines the clinical variability in MASA syndrome. DNA studies confirm linkage to DNA markers of the Xq28 region. Analysis of published cases with hereditary spastic paraplegia (HSP), where linkage studies have been carried out, emphasizes the clinical variability in MASA syndrome and other types of HSP, thus making a definite diagnosis in single cases often impossible.
Second meiotic nondisjunction of the rearranged chromosome in a familial reciprocal 5/13 translocation
Authors: Masuno Mitsuo , Cholsong Yang , Kuwahara Takashi , Shimizu Nobuo , Yamaguchi Seiji , Kawabata Ichiro , Tamaya Teruhiko , Morishita Yukio , Yoshimi Naoki , Orii Tadao
Published: June 2005

We describe a 20‐week‐gestation male fetus with partial dup(5p) and proximal dup(13q), 47,XY,t(5;13)(p15;q21), + der(13)t(5;13)(p15;q21) mat. This finding is attributable to second meiotic nondisjunction of the rearranged chromosome in a maternal balanced reciprocal translocation. To the best of our knowledge, there have been only 3 previous reports of a similar error in the segregation of the rearranged chromosomes. For the first time evidence has been given that this unusual segrgation is due to maternal second meiotic nondisjunction, using QFQ banding heteromorphisms. Second meiotic malsegregation should be taken into account in the consideration of reproductive problems in carriers of balanced translocations.
Nager acrofacial dysostosis: Male‐to‐male transmission in 2 families
Authors: Aylsworth Arthur S. , Lin Angela E. , Friedman Patricia A.
Published: June 2005

We describe 2 unrelated families with male‐to‐male transmission of Nager syndrome. All 5 affected individuals have moderate expression of the phenotype. One affected boy also has Hirschsprung disease. Although Nager acrofacial dysostosis usually occurs sporadically, both recessive and dominant inheritance have been suggested on the basis of reported familial cases. The 2 families described here with father‐to‐son transmission strongly support the hypothesis that some cases of Nager acrofacial dysostosis occur in individuals who are heterozygous for dominantly expressed, autosomal mutations.
Autosomal dominant macrocephaly: Benign familial macrocephaly or a new syndrome?
Authors: Cole T. R. P. , Hughes H. E.
Published: June 2005

During the course of a clinical study of Sotos syndrome, six out of 79 probands failed to fit the phenotype of Sotos syndrome but showed remarkable similarities to each other and to a further 11 first‐ and second‐degree relatives. Clinical features in these index cases included macrocephaly, > +3.5 SD; normal or near normal birth weight and length with subsequent relative obesity; variable developmental delay; and typical face, characterised by a square outline with frontal bossing, a “dished‐out” mid‐face, biparietal narrowing, and long philtrum. All recorded bone ages were less than the 75th centile, and two were below the 10th centile. The authors believe the original diagnosis was incorrect and that these cases likely represent a previously underscribed autosomal dominant macrocephaly syndrome.
Follow‐up of Ullrich's original patient with “Ullrich‐Turner” syndrom
Authors: Wiedemann H.‐R. , Glatzl J.
Published: June 2005

In 1930 Ullrich published the case of the prototype patient with what is now referred to as the Ullrich‐Turner syndrome. In 1987 this patient was restudied at the age of 66 years. She permitted a cytogenetic study, a brief clinical evaluation, and reported about her life and adjustments to her condition. This patient had the striking findings of adults with the Ullrich‐Turner syndrome and an unequivocal 45,X chromosome constitution in all cells examined, showing that she indeed has the Ullrich‐Turner and not the Noonan syndrome. She reached a maximum height of 144.5 cm, had primary amenorrhea, failure of maturation of secondary sexual characteristics, and yet in many personal and professional ways had adjusted admirably to her condition.
Autosomal recessive malformation syndrome with minor manifestation in the heterozygotes: A preliminary report of a possible new syndrome
Authors: Paes‐Alves Auristela F. , Azevêdo Eliane S. , Sousa Maria das Graças F. , Almeida‐Melo Neli , Oliveira‐Filho Osório J.
Published: June 2005

We describe 3 patients with a new malformation syndrome in 2 sibships in a large kindred from Bahia, Brazil. The parents in both sibships are consanguineous. The syndrome is characterized by malformations of the face, ears, hands and feet, plus mixed deafness and pseudopapilledema. Fifty‐four relatives were examined clinically and scored by the number of anomalies. A control sample of 54 individuals was equally examined. The distribution of the number of anomalies per individual (score) is bimodal in the relatives of the patients but unimodal in the control individuals. Detection of heterozygotes was based on the score distribution.
Etiologic complexities of diaphragmatic defects: Right diaphragmatic hernia, pulmonary hypoplasia/agenesis, and hydrocephalus in sibs
Authors: Bieber Frederick R. , Dawson Andrea E. , Holmes Lewis B.
Published: June 2005

Here we review the complexities of diaphragmatic defects and describe sibs with small, right diaphragmatic defects with pulmonary hypoplasia/agenesis and hydrocephalus. Despite a poor initial prognosis, the propositus has progressed remarkably well. Antenatal sonographic study detected hydrocephalus but not the diaphragmatic defect in the sib of the propositus. Because diaphragmatic defects are most commonly found in association with other anomalies and may occur in association with chromosome anomalies careful workup of all affected infants is crucial for accurate genetic counseling.
Goldberg–Shprintzen syndrome: Hirschsprung disease, hypotonia, and ptosis in sibs
Authors: Yomo Akihiro , Taira Takeyasu , Kondo Ikuko
Published: June 2005

We describe a brother and sister with Hirschsprung disease, hypotonia, and ptosis. Their condition resembles that in 2 sibs reported by Goldberg and Shprintzen. We conclude that the clinical characteristics in 8 reported cases with similar clinical manifestations represent a distinct autosomal recessive syndrome, Goldberg–Shprintzen syndrome.
Tapetoretinal degeneration in brothers with apparent Cohen syndrome: Nosology with Mirhosseini‐Holmes‐Walton syndrome
Authors: Steinlein O. , Tariverdian G. , Boll H. U. , Vogel F.
Published: June 2005

We report on 2 brothers with marked eye anomalies, documented with histopathological studies, and several other findings fitting the diagnosis of both the Cohen and the Mirhosseini‐Holmes‐Walton syndromes. In accordance with Norio and Raitta (Norio R, Raitta C (1986): Am J Med Genet 25:397–398) we come to the conclusion that these 2 syndromes constitute one clinical but possibly heterogeneous entity.
Prevalence of type I spinal muscular atrophy in North Dakota
Authors: Burd Larry , Short Sarah K. , Martsolf John T. , Nelson Richard A.
Published: June 2005

In order to establish the incidence and prevalence of type I spinal muscular atrophy (SMA Werdnig‐Hoffmann disease) in North Dakota, we reviewed the death certificates for the past 8 years. Between 1980 and 1987 the prevalence of was 1.5 per 10,000. The incidence was 1 in 6,720. This suggests a carrier frequency of 1 in 41 in North Dakota with a gene frequency of 0.0122. In North Dakota, type I spinal muscular atrophy appears to be 3 to 10 times more common than in other locations.
Monozygotic twins discordant for the major signs of McCune‐Albright syndrome
Authors: Endo Machiko , Yamada Yutaka , Matsuura Nobuo , Niikawa Norio
Published: June 2005

We describe a girl, one of monozygotic (MZ) twins, with endocrine dysfunction with precocious puberty, café‐au‐lait nevi and poly‐ostotic fibrous dysplasia (PFD), McCune‐Albright syndrome (MAS). After treatment with cyproterone acetate for 7 years the precocious puberty and excess growth improved but the bone‐age still remain advanced. The co‐twin had an advanced bone‐age and a small cafe‐au‐lait spot, but showed neither en‐docrinopathy nor fibrous dysplasia of bone. On the basis of the findings in these twins, together with those in previously reported fa‐milialcasesofMAS, includingtwopairsofMZ twins, a 2‐hit mutation hypothesis is proposed: a dominant mutation may be inherited and leads to PFD in offspring as the primary defect of MAS; the second mutation may occur in somatic cells leading to rnosaicism and thus resulting in MAS. This concept explains not only sporadic cases of MAS but also reported familial cases. If we assume that the second mutation occurred in an early somatic division, it would explain the discrepancy of clinical manifestations between MZ twins.
Twin fetuses with abnormalities that overlap with three midline malformation complexes
Authors: Hingorani Sangeeta R. , Pagon Roberta A. , Shepard Thomas H. , Kapur Raj P.
Published: June 2005

Twin fetuses aborted at an estimated gestational age of 145 days were concordant for oral, facial, skeletal, and central nervous system malformations. The twins were discordant for other anomalies including cardiac defects, polydactyly, and malrotated short bowel. The combination of malformations observed overlaps with that of the oral‐facial‐digital syndrome, hydrolethalus syndrome, and Pallister‐Hall syndrome. The problem of phenotypic overlap between these syndromes is discussed.
Apparent CHARGE association and chromosome anomaly: Chance or contiguous gene syndrome
Authors: Clementi Maurizio , Tenconi Romano , Turolla Licia , Silvan Carla , Bortotto Livio , Artifoni Lina
Published: June 2005

This report concerns 2 unrelated patients with apparent CHARGE association and a chromosome abnormality, resulting from different unbalanced familial translocations involving chromosomes 2 and 18 in one family, and chromosomes 3 and 22 in the other. Although the identification of two different chromosome abnormalities might be due to chance, the observation of a long arm deletion of chromosome 22 in patient 2 and of the frequent coexistence of CHARGE association and DiGeorge anomaly raise the possibility of a contiguous gene syndrome in at least some CHARGE cases.
Megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS), an autosomal recessive disorder: Clinical reports and review of the literature
Authors: Annerén Göran , Meurling Staffan , Olsen Leif
Published: June 2005

We present 2 new patients with the megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS), review the literature, and discuss the prenatal diagnosis and treatment. MMIHS, as reported in 43 cases, is usually lethal. Most children die during the first year of life, and only 3 children survived their first year. We report the 6th pair of sibs with the disease. Overall, 17 patients reported have had sibs with MMIHS or the parents were consanguineous; 4 times the parents were first, cousins, confirming that this is an autosomal recessive disorder. The present 2 children, whose parents also were first cousins, were of different sex. They had typical MMIHS with abdominal distension due to pronounced megacystis, hydronephrosis, microcolon, and microileum, involving the distal part of the ileum, malrotation of the gut, and intestinal hypoperistalsis. Neither surgery nor medical treatment was successful and the children died at the age of 19 days and 21/2 months, respectively. There is no cure for the disease. However, a new prokinetic drug, Cisapride® might be worth trying in these cases. Prenatal ultrasound diagnosis of MMIHS might be possible.
Fryns syndrome without diaphragmatic hernia?
Authors: Willems Patrick J. , Keersmaekers Guy H. A. , Dom Koen E. , Colpaert Cecile , Schatteman Etienne , Vergote Ignace B. P. , Dumon Jan E.
Published: June 2005

We report on a child with Fryns syndrome including lung hypoplasia, characteristic facial appearance, cleft palate, cardiac anomaly, distal limb abnormalities, absent nipples, bicornuate uterus and early death. In contrast to most patients with Fryns syndrome, diaphragmatic hernia was absent in our patient. However, the diaphragm was reduced to a fibrous web with reduced muscular component.
Familial holoprosencephaly, heart defects, and polydactyly
Authors: Hennekam Raoul C. M. , Van Noort Gerard , De La Fuente Alfred A.
Published: June 2005

We describe a pair of sibs with microcephaly, hypoplastic nose, cleft lip/palate, a complicated Fallot‐like cardiac defect, and holoprosencephaly and polydactyly. One sib appeared to have normal chromosomes. The healthy parents were second cousins. This constellation of signs has been described before in at least 14 other patients, and was possibly present in several others. Although there is overlap with a number of similar conditions, especially hydrolethalus syndrome, this probably represents a separate entity. Three pairs of sibs and consanguinity in 3 families point to autosomal recessive pattern of inheritance.
Duplication (6q) syndrome diagnosed in utero
Authors: Uhrich Stefanie , FitzSimmons Jack , Easterling Thomas R. , Mack Laurence , Disteche Christine M.
Published: June 2005

We report on a case of partial duplication 6q detected ultrasonographically. The clinical picture noted in utero is consistent with the adult phenotype previously reported in the literature.
Molecular and cytologic studies of Ehlers‐Danlos syndrome type VIII
Authors: Biesecker L. G. , Erickson R. P. , Glover T. W. , Bonadio J.
Published: June 2005

We present a family with findings of Ehlers‐Danlos syndrome type VIII and a presenile appearance due to decreased subcutaneous tissue with drawn skin, defective wound healing, contractures, and thin hair. To investigate this syndrome, we studied collagen production and the growth properties of cultured fibroblasts taken from affected relatives. We could not find evidence of a collagen defect or premature senescence of cultured fibroblasts, although the fibroblasts may have a decreased growth rate. We conclude that this family has findings of EDS VIII and premature aging and propose that this overlapping phenotype is due to a single pathogenetic mechanism. Our studies of collagen production and fibroblast replication did not discern this mechanism.
Sporadic, idiopathic MCA syndrome with mandibulofacial dysostosis and tibial hemimelia
Authors: Richieri‐Costa A. , Guion‐Almeida M. L. , van den Ende J.
Published: June 2005

We report on a Brazilian woman with mandibulofacial dysostosis, cleft lip/palate, vertebral anomalies, abnormally modeled femora, and bilateral tibial agenesis. The clinical aspects involving this patient strongly suggest an unreported condition. Clinical and genetic aspects are discussed.
Neural tube and neural crest: A new view with time‐lapse high‐definition photomicroscopy
Authors: Jaskoll Tina , Greenberg Gary , Melnick Michael
Published: June 2005

The dynamic process of neural tube formation and neural crest migration in live, unstained cultured avian embryos at Hamburger‐Hamilton (H.H.) stages 8–11 was investigated by time‐lapse cinematography using a high‐definition microscope. These studies have demonstrated that neural tube closure in the trunk region differs from that observed in the head. The cephalic neural folds elevate slowly, then make contact rapidly. Following this initial apposition, they gradually “zip‐up” in the rostrad and caudad direction. In the trunk region where the neuroepithelium bulges adjacent to the somites, the edges of the folds pulsate and forcefully touch‐retract‐touch in these bulging regions; the intersomitic epithelia retract, remain open even after more posterior somitic regions have apposed, and then close slowly. Epithelial blebs and N‐CAM antibody were observed at the leading edges of the neuroepithelia. Between the open folds only a few bridging cells were seen; they probably represent the sites of initial cell adhesion following epithelial retraction. Focusing into the developing embryo shows that neuroepithelial fusion occurs prior to surface epithelial fusion. A meshwork of synchronously pulsating neural crest cells was identified below the surface epithelium and a preliminary investigation of their initial migration was conducted.
Pelizaeus‐merzbacher disease: Clinical and DNA‐linkage study of an extended family
Authors: Johnson Virginia P. , Carpenter Nancy J. , Alan Kelts K.
Published: June 2005

We describe a 5‐generation family of 6 individuals with Pelizaeus‐Merzbacher disease, Type I. DNA linkage study was done to establish carrier status. Two loci, DXS162 and DXYS1, were informative in this family for carrier determination. The highest lod score is that for PMD‐DXYS1 (Z= 1.421 at θ = 0). The carrier probability can only be defined as likely or unlikely in the absence of an established recombination frequency.
Cartilage hair hypoplasia, metaphyseal chondrodysplasia type McKusick: Description of seven patients and review of the literature
Authors: Burgt Ineke Van Der , Haraldsson Asgeir , Oosterwijk Jan C. , van Essen Anthonie J. , Weemaes Corry , Hamel Ben
Published: June 2005

We describe 7 cases of cartilage hair hypoplasia (CHH) with emphasis on the clinical and immunological aspects. The literature on CHH is reviewed and symptoms in 63 nonAmish cases are summarized.

In this autosomal recessive disorder the immunodeficiency, hair abnormalities, and severity of skeletal involvement show extremely variable expressivity, between and within families. Two of the 3 sib‐pairs among our cases demonstrate the great difference in expression within one family. At adult age roentgenological abnormalities can be very mild, or even absent. An impairment in cellmediated immunity is present in all of our cases and seems a consistent manifestation in CHH; however, sometimos it is very subtle and without clinical symptoms.
Autosomal recessive ectodermal dysplasia: I. An undescribed dysplasia/malformation syndrome
Authors: Bustos Tania , Simosa Venancio , Pinto‐Cisternas Juán , Abramovits William , Jolay Liliana , Rodriguez Luis , Fernandez Luis , Ramela Marcos
Published: June 2005

We describe‐27 individuals of 7 families related to each other with high probability who showed manifestations of ectodermal dysplasia and other anomalies affecting females as severely as males with variable expressivity. All parents were normal. These families were detected in a relatively isolated and inbred population with very small neighbouring communities from a Carribbean Sea island, Margarita Island, in Northeastern Venezuela (Nueva Esparta State).

The clinical picture common to all patients could not be classified within the heterogeneous group of known ectodermal dysplasias and the published cases do not resemble our patients.

We believe that this condition constitutes a newly recognized autosomal recessive dysplasia/malformation syndrome of ectodermal dysplasia.
First report of management and outcome of pregnancies associated with hereditary orotic aciduria
Authors: Bensen Jeannette T. , Nelson Lewis H. , Pettenati Mark J. , Block Steven M. , Brusilow S. W. , Livingstone Laura R. , Burton Barbara K.
Published: June 2005

Two pregnancies in a 25‐year‐old woman with hereditary orotic aciduria who was managed prenatally on uridine therapy are described. The first pregnancy resulted in an infant with multiple congenital anomalies and a 47, xx, inv(4)(p12q25), + der(22)t(11;22)(p23;q11) karyotype. The proposita was found to be a carrier of a de novo 11;22 translocation and a pericentric inversion of chromosome 4. Subsequently, several carriers of orotic aciduria in this family were identified with the inverted chromosome 4. The second pregnancy resulted in a normal male with an inverted chromosome 4.
True agonadism: Report of a case analyzed with Y‐specific DNA probes
Authors: Maciel‐Guerra Andréa T. , Farah Solange B. , Garmes Heraldo M. , Pinto Walter , Da Silva Joaquim M. Bustorff , Baptista Maria Teresa , Marques‐de‐Faria Antonia Paula , Guerra Gil , De Mello Maricilda P.
Published: June 2005

We report on a 5‐year‐old girl with a male karyotype (46, XY), severe psychomotor and physical retardation, minor anomalies, and female external genitalia with a blindly ending vagina. She has normal adrenal function, prepubertal serum gonadotropin and testosterone levels, which did not rise after hCG stimulation. On abdominal exploration no gonads were found, and only mesonephric and Müllerian remnants. She was HY positive, and no deletion was detected in the Y chromosome using 5 different probes. Although a genetic defect is not excluded, pregnancy complications suggest an environmental insult to the developing testes.
Gardner syndrome in a boy with interstitial deletion of the long arm of chromosome 5
Authors: Kobayashi Tatsunori , Narahara Kouji , Yokoyama Yuji , Ueyama Satoshi , Mohri Osamu , Fujii Takao , Fujimoto Makoto , Ohtsuki Shin‐Itchi , Tsuji Kazushiro , Seino Yoshiki
Published: June 2005

We described a 15‐year‐old boy with Gardner syndrome (GS), mental retardation, and craniofacial abnormalities. High‐resolution banding analysis showed an interstitial deletion of the long arm of chromosome 5 (q22.1→q31.1). The breakpoints in the present case and in 3 previously reported 5q‐ patients with adenomatous polyposis coli suggest that the gene responsible for GS/or familial polyposis coli (FPC) is in the 5q22 region, a result consistent with the findings of linkage studies.
Essential osteolysis associated with nephropathy, corneal opacity, and pulmonary stenosis
Authors: Shinohara Osamu , Kubota Chidori , Kimura Mikio , Nishimura Gen , Takahashi Shori
Published: June 2005

We report on 5‐year‐old girl with essential osteolysis, nephropathy, corneal opacity, and valvular pulmonary stenosis. The patient was initially seen for evaluation of flexion contractures at wrists, elbows, and knees. Radiographic examination showed osteolytic changes primarily involving the hands and feet. She had persistent proteinuria; renal biopsy disclosed focal glomerulosclerosis in 1/3 of glomeruli. Electron microscopic study of skin fibroblast showed dilated and vacuo‐lated rough endoplasmic reticulum. To our knowledge essential osteolysis associated with the aforementioned disorders has not been previously reported.
Hallermann–Streiff syndrome: A review
Authors: Cohen M. Michael
Published: June 2005

The Hallermann–Streiff syndrome is characterized by dyscephaly, hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, and proportionate short stature. Cause is unknown; sporadic occurrence is the rule. Data presented in this review include the characteristics of pregnancy, growth and development, principal manifestations, radiographic and ophthalmological characteristics, and the results of cephalometric study. Potential complications in the syndrome are related to the narrow upper airway associated with the craniofacial configuration. Severe complications may include early pulmonary infection, respiratory embarrassment, obstructive sleep apnea, and anesthetic risk. Topics for future study are suggested.
Radiological findings in Hallermann–Streiff syndrome: Report of five cases and a review of the literature
Authors: Christian Cathy L. , Lachman Ralph S. , Aylsworth Arthur S. , Fujimoto Atsuko , Gorlin Robert J. , Lipson Mark H. , Graham John M.
Published: June 2005

Hallermann‐Streiff syndrome (HSS) is a rare disorder with an associated constellation of radiological findings that may aid in the diagnosis of affected individuals. We reviewed the skeletal surveys of 5 affected individuals and noted some characteristic and constant findings. Radiological findings can include a large, poorly ossified skull with decreased ossification in the sutural areas. There was an increase in the number of Wormian bones. Severe mid‐facial hypoplasia was present along with a prominent nasal bone. The skull films also showed an abnormally obtuse or nearly straight gonial angle. The teeth appeared small. The long bones were thin and gracile in appearance and often showed poor demarcation of the cortex from the medullary portion. Abnormal bowing of the radius and ulna was seen neonatally in 2 cases. There was widening at the metaphyseal ends of the long bones. The ribs were thin, but normal in length. The vertebral bodies were noted to be small and 3 cases had platyspondyly. There was a decreased number of sternal ossification enters. The metacarpals were also thin and gracile in appearance with metaphyseal widening. We conclude that these characteristic radiological findings in the newborn with HSS can aid in the diagnosis, and a skeletal survey in suspected individuals may be valuable in confirming the diagnosis.
Hallermann–Streiff syndrome: Clinical and psychological findings in children. Nosologic overlap with oculodentodigital dysplasia?
Authors: Spaepen Ann , Schrander‐Stumpel Constance , Fryns Jean‐Pierre , De Die‐Smulders Christine , Borghgraef Martine , Van Den Berghe Herman
Published: June 2005

We describe 3 young children with Hallermann–Streiff syndrome, 2 with typical manifestations and 1 with the facial changes without the eye abnormalities but with a cleft palate and with complete syndactyly of fingers IV and V. The latter case represents overlap of the Hallermann–Streiff syndrome and oculodentodigital dysplasia. “Dwarfism” as a possible clinical risk marker of mental retardation is discussed. As cause, a mendelian autosomal dominant mutation seems most probable.
On lumping and splitting: A fetus with clinical findings of the oral‐facial‐digital syndrome type VI, the hydrolethalus syndrome, and the Pallister‐Hall syndrome
Authors: Muenke Maximilian , Ruchelli Eduardo D. , Rorke Lucy B. , McDonald‐McGinn Donna M. , Orlow Michael K. , Isaacs Ann , Craparo Frank J. , Dunn Linda K. , Zackai Elaine H.
Published: June 2005

The three midline malformation complexes, the oral‐facial‐digital syndrome type VI (OFDS VI) or Váradi syndrome, the hydrolethalus syndrome (HS), and the Pallister‐Hall syndrome (PHS) have been described as distinct genetic entities. Here, we report a fetus with a combination of clinical findings of all 3 syndromes similar to the twin fetuses described in the accompanying paper (Hingorani et al., 1991). The phenotypic overlap in these fetuses with the OFDS VI, HS, and PHS raises the question as to whether or not they indeed represent separate genetic entities as previously assumed.
GMS syndrome: A new dominant condition with goniodysgenesis, mental retardation, and short stature
Authors: Kupchik Gabriel S. , Ludman Mark D. , Raab Edward L. , Gilbert Fred
Published: June 2005

We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature.

The pattern of occurrence is compatible with either autosomal dominant or X‐linked inheritance.
Deletion of the proximal short arm of chromosome 8
Authors: Stratton Robert F. , Crudo David F. , Varela Maria , Shapira Emmanuel
Published: June 2005

We report on a 5‐month‐old boy with a de novo interstitial deletion of the proximal short arm of chromosome 8 (p21p11.2). He manifested bilateral cleft lip and palate, and apparent hypogonadism. Four previous case reports with similar deletions (p11.1p21) were associated with hypogonadotropic hypogonadism [Beighle et al., Hum Genet 38:113–121, 1977] and hereditary spherocytosis (HS) [Chilcote et al., Blood 6:156–159, 1987; Kitatani et al., Hum Genet 78:94–95, 1988; Lux et al., Nature 345:736–739, 1990]. Our patient has no demonstrable red blood cell abnormality, suggesting that the gene for HS is located in the region 8p11.1 to 8p11.2.
Cockayne syndrome: Review of 140 cases
Authors: Nance Martha A. , Berry Susan A.
Published: June 2005

To define diagnostic criteria for Cockayne Syndrome (CS) and to identify in detail the complications of the condition, a comprehensive review of 140 cases of CS was performed. Criteria required for the diagnosis include poor growth and neurologic abnormality; other very common manifestations include sensorineural hearing loss, cataracts, pigmentary retinopathy, cutaneous photosensitivity, and dental caries. The mean age of death in reported cases is 123/12 years, though a few affected individuals have lived into their late teens and twenties. Prenatal growth failure, congenital structural eye anomalies, severe neurologic dysfunction from birth, and the presence of cataracts within the first 3 years of life are predictors of severe disease and early death. In contrast with other disorders of chromosome or DNA repair, cancer has never been reported in a classical CS patient, and there appears to be no predisposition to infectious complications. The wide spectrum of symptoms and severity of the disease suggest that biochemical and genetic heterogeneity exist. CS is an uncommon but devastating genetic condition which will be better understood as the biochemical interrelationships between DNA replication and repair, and between growth, homeostasis, and oncogenesis are unraveled.
Agonadism in a 46,XY patient with CHARGE association
Authors: Kushnick Theodore , Wiley John E. , Palmer Shane M.
Published: June 2005

We report on an infant girl born with findings of CHARGE association who proved to be a genetic male (46, XY) on cytogenetic study. Further investigation of the genitalia demonstrated partially female internal organs but absence of gonads by ultrasonography, hormone studies, and absence of ZFY by DNA probe of Yp. Pelvic exploration confirmed lack of gonadal tissue and uterus. Facial phenotype was compatible with CHARGE appearance.
46,XX pure gonadal dysgenesis with growth hormone deficiency and impaired 3β‐hydroxysteroid dehydrogenase activity
Authors: Sills Irene N. , Rapaport Robert , Skuza Kathryn A. , Horlick Mary N. B.
Published: June 2005

Patients with 46,XX pure gonadal dysgenesis generally are of normal stature and have less than usual amounts of pubic and axillary hair. We report on a patient who presented at age 11.9 years with short stature, absence of breast development, and excessive pubic hair. Her karyotype in leukocytes, fibroblasts, and streak gonad was 46,XX. The patient was diagnosed as having growth hormone deficiency. Elevated ACTH stimulated levels of 17‐hydroxypregnenolone and dehydroepiandrosterone and elevated ACTH stimulated ratio of 17‐hydroxypregnenolone to 17‐hydroxyprogesterone suggested inadequate adrenal 3β‐hydroxysteroid dehydrogenase activity. Treatment with growth hormone resulted in improvement in growth velocity and replacement with estrogen in feminization. We suggest that the finding of short stature in patients with 46, XX pure gonadal dysgenesis should not be attributed to the syndrome, but rather requires investigation for possible growth hormone deficiency. The poor growth of our patient prior to growth hormone replacement implies that dehydroepiandrosterone, unlike testosterone and estrogen, is ineffective in promoting linear growth in the absence of adequate growth hormone.
Phenotypically dissimilar hypophosphatasia in two sibships
Authors: Macfarlane J. D. , Kroon H. M. , van der Harten J. J.
Published: June 2005

Autosomal dominant and autosomal recessive forms of hypophosphatasia have been reported; generally the clinical picture runs true to form in families. In each of 2 kindreds, 2 sibs were clinically affected by hypophosphatasia to a markedly different extent. One set of sibs showed the lethal (perinatal) and infantile forms. The other showed the dental and adult forms. In both families there was consanguinity, albeit distant, and clinical expression in sibs supporting autosomal recessive inheritance.
Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: Prenatal diagnosis, clinical and pathological findings
Authors: Corsello Giovanni , Maresi Emiliano , Rossi Cinzia , Giuffrè Liborio , Cittadini Ettore
Published: June 2005

We present male monozygotic twins with thanatophoric dysplasia (TD) type I concordant for long bone abnormalities and discordant for cloverleaf skull. The twins were the product of the second pregnancy of unrelated parents, with advanced paternal age. Prenatal diagnosis and postmortem examination showed severe rhizomelic shortness of limbs, bowing of the long bones with “telephone‐receiver” femora in both twins, and cloverleaf skull and hydrocephalus in one of them. It is now accepted that most of cases of TD, such as in the present report, represent an autosomal dominant mutation with a high new mutations rate.
Effect of heterogeneity and assumed mode of inheritance on lod scores
Authors: Durner Martina , Greenberg David A.
Published: June 2005

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer‐simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families.

When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families.

The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.

The estimate of the recombination fraction became larger as the proportion of recessive or dominant unlinked families increased, but, in general, sporadic families had less influence on the estimate of the recombination fraction than did unlinked families with genetic disease.

The assumed penetrance that led to the highest maximum lod score occurred close to the value which was used to generate the data. There was more variation as the proportion of linked families in the data sets decreased.
Congenital synspondylism
Authors: Wiles Catherine R. , Taylor Thomas F. K. , Sillence David O.
Published: June 2005

We present 3 patients with a specific pattern of congenital familial extensive vertebral anomalies (CFEVA) with vertebral and carpal coalition. It is proposed that these patients and two previously reported cases have a vertebral disorder akin to symphalangism in the fingers. The name synspondylism is proposed. Two instances of sib recurrence point to Mendelian segregation in some instances of synspondylism. The syndromes and associations encompassed by CEFVA are reviewed. The clinical and radiographic manifestations of congenital synspondylism are discussed in the perspective of the possible pathogenesis of segmentation disorders of the spine.
Trisomy 16p in a liveborn infant and review of trisomy 16p
Authors: O'Connor Timothy A. , Higgins Rodney R.
Published: June 2005

We report on an infant boy with duplication of part of 16p and partial deficiency of 9p:46.XY, −9, + der(9)t(9;16)(p24;p13.1)mat. The child has the typical phenotype of dup(16p) even though the extra piece of 16p is small (16pl3.1→pter). Manifestations include severe developmental delay, rounded face, sparse hair, ear anomalies, hypertelorism, cleft soft palate, a thin vermilion border of the upper lip, and left renal dysgenesis. We review 16p duplications.
Autosomal dominant inheritance of Klein–Waardenburg syndrome
Authors: Sheffer Ruth , Zlotogora Joel
Published: June 2005

We report on 2 sibs with the Klein–Waardenburg syndrome; they had dystopia canthorum, blepharophimosis, and bilateral flexion contractures of the fingers. The children's father and paternal aunt are also affected. This report confirms that the Klein–Waardenburg syndrome is an autosomal dominant syndrome.
Duplication of distal 19q: Clinical report and review
Authors: Boyd Ellen , Grass Frank S. , Parke James C. , Knutson Kam , Stevenson Roger E.
Published: June 2005

We report on a 20‐month‐old boy with duplication of the distal part of 19q. His karyotype is 46, XY, −22, + der(22), t(19;22) (q13.3; p11.2)mat. The propositus has multiple minor anomalies, congenital heart defects, seizures, profound psychomotor retardation, and growth impairment. These characteristics are similar to those in the other 10 reported cases of distal 19q duplication and help delineate the phenotype. A review of the literature is presented.
Syndrome of microcephaly, Brachmann–de Lange‐like facial changes, severe metatarsus adductus, and developmental delay: Mild Brachmann‐de Lange syndrome?
Authors: Halal Fahed , Silver Kenneth
Published: June 2005

We report on 4 individuals (3 sibs and their father) with a syndrome of growth retardation, microcephaly, minor facial anomalies reminiscent of a mild Brachmann–de Lange syndrome (BDLS), severe metatarsus adductus, developmental delay, and unusual dermatoglyphics. The syndrome, which seems to be inherited as an autosomal dominant trait with variable expressivity, resembles mild BDLS.