bluuebunny/crossref_metadata_2025 huggingface dataset:
The fra(X) syndrome: Neurological, electrophysiological, and neuropathological abnormalities
Authors: Wisniewski K. E. , Segan S. M. , Miezejeski C. M. , Sersen E. A. , Rudelli R. D.
Published: June 2005

We have evaluated 62 fragile X syndrome [fra(X)] individuals (55 males and 7 females) with different degrees of developmental disabilities that were clinically non‐progressive and non‐focal in character. The mean age for the 55 males was 23.1 years ± 14.3 SD with a range of 2–70: for the 7 females, the mean age was 15.7 years ± 3.5 SD with a range of 10–20 years. Mental retardation (MR) was found in 53 males (8/53 [15.1%] mild, 26/53 [49.1%] moderate, 14/53 [26.4%] severe, and 5/53 [9.4%] profound). Learning disabilities were found in 2/55 (3.6%) of males. One of the 7 females had mild and one had moderate MR: the other 5 were learning disabled. Autistic stigmata were present in 10/62 (16%) of the patients. Only 14/62 (23%) had a history of seizures, all of which were controlled with anticonvulsants. In 36/62 cases, an electroencephalogram (EEG) was performed. We compared these data with that of others. Brain stem auditory evoked response (BAER) was performed in 12 cases. Abnormalities were found in only 5/12. Neuroimaging and computerized cranial transaxial tomography (CT scan) were performed on 21/62 (34%) of the patients. Only 8 of these 21 (38%) studies were abnormal. One patient died; neuropathological studies showed mild brain atrophy, with light microscopic and ultrastructural abnormalities. Rapid Golgi dendritic spine patterns showed that the proximal apical segments were abnormally developed. Very thin, long tortuous spines with prominent terminal heads and irregular dilatations were present. Marked reductions in the length of the synapses, as determined on EPTA‐postfixed tissue where noted. The mean synaptic contact area was 35% shorter than the normal length observed in controls. In summary, the neurological abnormalities are mainly in the cognitive function, seizures appear similar to the benign age‐related epilepsies, whereas the neuropathological abnormalities are in the wiring system, showing synaptic dysgenesis.
Relationship between age and IQ among fragile X males: A multicenter study
Authors: Fisch Gene S. , Arinami Tadao , Froster‐Iskenius Ursula , Fryns Jean‐Pierre , Curfs L. M. , Borghgraef M. , Howard‐Peebles Patricia N. , Schwartz Charles E. , Simensen Richard J. , Shapiro Lawrence R.
Published: June 2005

Longitudinal decline in IQ among fragile X males was reported recently. However, there are problems in retesting IQ that may affect scores. Two such factors are intertest time interval and score obtained on the first test. To determine the generality of IQ score changes, we examined 101 fragile X males from 6 centers. To ensure high test‐retest reliability, only results from Stanford‐Binet and Wechsler tests were used. Thus there were retest scores from 60 subjects. Test‐retest reliability between first and last scores was very good (r = 0.85) and comparable to those seen in nonfragile X mentally retarded individuals. Also computed were z‐scores of differences in IQ scores. The z‐score differences were distributed about a mean at 1 SD below the expected zero value. Eighteen subjects showed statistically significant decreases in IQ, 6 showed statistically significant increases, while 5 showed the same scores. Z‐score differences were not correlated with type of residence or elapsed intertest interval, but were negatively correlated with first score obtained, indicating a regression‐to‐the‐mean effect. Using a multiple regression analysis, we found first score obtained, age tested, and age retested significant predictors of score differences, accounting for 19% of the total variance. These results suggest that factors previously identified as affecting retest scores have a smaller effect than originally thought. It is suspected that decline in IQ is associated with dynamic neurological processes and needs to be investigated further.
Short‐term memory and cognitive variability in adult fragile X females
Authors: de von Flindt Robert , Bybel Bohdan , Chudley Albert E. , Lopes Fatima
Published: June 2005

We investigated the possibility that adult fragile X [fra(X)] heterozygotes have a distinct or specific cognitive profile, with a particular focus on visuospatial and/or memory deficits. With a sample of 13 adult fra(X) female carriers (2 fra(X) positive) and age‐matched control women, we performed 2 tests: Wechsler Adult Intelligence Scale‐Revised (WAIS‐R) and the Revised Visual Retention Test (RVRT). An identifiable cognitive profile was not evident in the study group, but significant differences were evident in RVRT performance in number correct and number of errors when compared to controls and normative data. The combination of the WAIS‐R and RVRT data suggests that the short‐term memory component of the tasks may be of more significance than visuospatial performance in the deficits observed.
Cognitive profiles associated with the fra(X) syndrome in males and females
Authors: Freund Lisa S. , Reiss Allan L.
Published: June 2005

Twenty‐three fragile X [fra(X)] males (mean IQ 50, mean age 10 years) and 11 fra(X) females (mean IQ 84, mean age 11.3 years) were administered the Stanford‐Binet Intelligence Scale, 4th ed. (S‐B). The cognitive profiles generated from the S‐B indicated a pattern of subtest strengths and weaknesses that was similar for both groups. Consistent weaknesses in both groups were found in quantitative skills and short‐term memory recall for visually presented, abstract stimuli, whereas a consistent strength was observed for short‐term memory recall of visually presented, meaningful stimuli. Strengths in verbal labeling and comprehension and deficits in spatial visualization and visual‐motor coordination were identified by the S‐B for the male group but not for the female group. Fragility in the female group was negatively correlated with the S‐B score for the short‐term memory area and the combined S‐B scores for the verbal reasoning and quantitative reasoning areas. The specific, S‐B‐identified cognitive strengths and weaknesses associated with the fra(X) condition are potentially useful indicators for investigation of specific cognitive process deficits associated with the fra(X) condition and the design of appropriate educational interventions for fra(X) children.
A distinct type of hidrotic ectodermal dysplasia
Authors: Halal Fahed , Setton Nora , Wang Nai‐San
Published: June 2005

Four individuals from 2 generations of a family had a hidrotic type of ectodermal dysplasia (ED). Males and females were similarly affected. They had trichodysplasia, with absent eyebrows and eyelashes; normal teeth, on‐ychodysplasia; normal sweating; mild retrognathia; abnormal dermatoglyphics; and mental retardation. Additional variable manifestations included irregular menses, high implanted or prominent ears, café‐au‐lait spot, keratosis pilaris, supernumerary nipple, and mild hearing loss. Their previously undescribed condition could be classified as an ED of 1–3 (trichoonychial) subgroup of group A according to Freire‐Maia's classification and is inherited as an autosomal recessive trait.
Association of distal arthrogryposis, mental retardation, whistling face, and pierre robin sequence: Evidence for nosologic heterogeneity
Authors: Schrander‐Stumpel Constance , Fryns Jean Pierre , Beemer Frits A. , Rive Frans A.
Published: June 2005

We report on 3 unrelated patients with the heterogeneous fetal hypokinesia sequence. They have distal arthrogryposis, severe developmental retardation, facial anomalies as seen in the Freeman‐Sheldon syndrome (“whistling face”), and Pierre Robin sequence. The present cases show a remarkable clinical resemblance to the 3 sibs described by Illum et al. (Illum N, Reske‐Nielsen E, Skovby F, Askjaer SA, Bersen A 1988: Neuro‐pediatrics 19:186–192), where calcium deposits were found in the nervous system and skeletal muscle. The presence of severe to profound developmental retardation in the present 3 patients is equally in favour of a central nervous system abnormality as the pathogenetic basis of the fetal hypokinesia sequence with secondary facial changes and distal arthrogryposis.
Interstitial deletion of the long arm of chromosome 6 associated with absent pulmonary valve
Authors: Horigome Hitoshi , Takano Takako , Hirano Takeki , Kajima Takako , Ohtani Shin‐Ichi
Published: June 2005

We report on a newborn infant with a deletion of 6q and absent pulmonary valve. His chromosome constitution was 46, XY,del (6) (q15q21). To our knowledge this is the first case with such combination. Some of his clinical features were found in common in 2 previous 6q – cases with the same breakpoints.
Huntington disease and childhood‐onset Tourette syndrome
Authors: Kerbeshian Jacob , Burd Larry , Leech Cindi , Rorabaugh Anne
Published: June 2005

A 40‐year‐old man with childhood‐onset Tourette syndrome (TS) developed Huntington disease (HD). We believe this to be the first reported case of childhood‐onset TS with adult onset HD. Discovery of other cases with both disorders may provide clues to the pathophysiology of both conditions.
Maternal muscle biopsy in X‐linked recessive centronuclear (myotubular) myopathy
Authors: Breningstall Galen N. , Grover Warren D. , Marks Harold G.
Published: June 2005

Muscle biopsy was used to attempt determination of carrier status in mothers and maternal relatives of patients with severe neonatal centronuclear (myotubular) myopathy, an X‐linked recessive disorder. We report findings from muscle biopsies of 3 mothers, one an obligate carrier. All biopsies showed abnormalities of nonspecific character. Whether such abnormalities assist in defining carrier status is uncertain. A more specific tissue marker for this disorder is required before muscle biopsy will facilitate carrier identification.
Risks associated with an elevated amniotic fluid α‐fetoprotein level
Authors: Crandall Barbara F. , Matsumoto Myles
Published: June 2005

Two and two‐tenths percent of 85,000 consecutive amniotic fluid (AF) samples had α‐fetoprotein (AFP) levels ≥ 2.0 MoM. Half measured 2.0–2.4 MoM, and 93% had a normal outcome. Sixty‐seven percent of those with higher levels had abnormalities. A positive acetylcholinesterase (AChE) increased the risk from 67% for levels between 2.0 and 2.4 MoM to 99% at ≥ 5.0 MoMs. After a normal ultrasound and chromosome studies, the risk for a fetal abnormality was 1% for AF AFP measuring 2.0–2.4 MoM and 3% for higher levels.
Three years' experience with neonatal screening for Duchenne/Becker Muscular dystrophy: Gene analysis, gene expression, and phenotype prediction
Authors: Greenberg Cheryl R. , Jacobs Hans K. , Halliday William , Wrogemann Klaus
Published: June 2005

Neonatal screening for Duchenne/Becker Muscular dystrophy (DMD/BMD) was begun as a pilot program on January 1, 1986. The aim of this program was to reduce the incidence of this X‐linked recessive degenerative neuromuscular disease. The neonatal detection of a boy with DMD allows early identification of carriers and genetic counselling. This may avert the birth of other affected males born prior to clinical diagnosis of DMD in the propositus at about age 5 years. Between January 1, 1986, and December 31, 1988, we identified and characterized a cohort of 8 asymptomatic infant boys with grossly elevated levels of creatine kinase, an active primary dystrophic process of muscle and complete dystrophin deficiency. Five of 8 males have detectable DNA alterations involving the DMD/BMD locus. Based on current hypotheses, characterization of dystrophin expression of this cohort allows us to predict a DMD phenotype in all 8 boys. To date, no additional males with DMD have been born in these families. Prospective follow‐up will allow us to test the validity of dystrophin testing in predicting the clinical course and impact of this program on reproductive decision making in these families.
Familial congenital micromelic dysplasia with dislocation of radius and distinct face: A new skeletal dysplasia syndrome
Authors: Borochowitz Zvi , Barak Mila , Hershkowitz Silvia
Published: June 2005

Recently Maroteaux et al. [Am J Med Genet 32:371–375] described omodysplasia as a new distinct congenital bone disorder in 3 cases; autosomal dominant inheritance was suggested. In this same report, 2 other cases (patients 4 and 5) presented with the same facial and upper limb anomalies, but were also noted to have severe shortness of lower limbs. The authors considered all 5 cases to represent variable expressivity of the same disorder, namely, omodysplasia. Here we report 4 patients (3 survivors), offspring of consanguineous Arabic‐Moslem couples. All presented at birth with severe short limb dwarfism and facial and radiologic appearance quite distinct from the first 3 patients of Maroteaux et al. [1989] with so‐called omodysplasia. Thus, we suggest that our 4 cases and patients 4 and 5 of Maroteaux et al. [1989] represent a distinct, previously unpublished bone dysplasia.
Sex chromosome marker: Clinical significance and DNA characterization
Authors: Johnson Virginia P. , McDonough Paul G. , Cheung Sau W. , Sun Li
Published: June 2005

Two patients are described with a virtually identical marker sex chromosome that was so small as to defy classification by conventional cytogenetic studies. DNA hybridization with Y probes allows classification into Y or non‐Y, and in situ hybridization with X centromere specific sequences, into X or non‐X. One patient was proven to have a Y fragment, and the second, an X fragment. DNA characterization is important since prognosis and clinical management depends on proper identification of the small marker sex chromosome.
Hereditary hypotrichosis of the scalp
Authors: Hess Russell O. , Uno Hideo
Published: June 2005

Hypotrichosis of the scalp was found in 4 individuals of a 6‐generation Caucasian family. This congenital phenomenon is a rather rare subtype of hereditary hypotrichosis and affects only scalp hair. The hairs of the scalp were generally sparse and short vellus type from childhood and thinned progressively with age. Morphologic studies showed poor imbrication of cuticles and dysplastic bulbar structure of the anagen follicles. The density of hair follicles per/cm2 area was comparatively lower than that of normal individuals. The genealogical study and histomorphometrical findings of this autosomal dominant trait are discussed along with previously reported causes of hypotrichosis.
Partial deletion of chromosome 6p: Delineation of the syndrome
Authors: Palmer Catherine G. , Bader Patricia , Slovak Marilyn L. , Comings David E. , Pettenati Mark J.
Published: June 2005

Here we summarize the clinical findings of five new patients and nine patients reported in the literature with deletions of the short arm of chromosome 6. The del(6p) syndrome appears to include the following clinical findings: mental retardation, microcephaly, abnormal sutures, broad nasal bridge, various eye and ear abnormalities, a short neck with excess skin folds, and a normal birth weight and length.
Unique dwarfing, spondylometaphyseal skeletal dysplasia, with joint laxity and dentinogenesis imperfecta
Authors: Goldblatt Jack , Carman Paul , Sprague Paul
Published: June 2005

We report a 3½‐year‐old boy with a unique spondylometaphyseal dysplasia with predominantly mesomelic involvement. In addition, he had gross generalised joint laxity and dentinogenesis imperfecta.
Tourette syndrome and autistic disorder: A significant relationship
Authors: Sverd Jeffrey
Published: June 2005

The histories of 10 children with autistic disorder or pervasive developmental disorder (PDD) cooccurring with familial Tourette syndrome (TS) are presented. Evidence from the histories of the patients and their relatives combined with other reports of cases of cooccurrence of TS and autism provides support for the hypothesis that TS may be responsible forcases of coocurrence of the disorders, contributes significantly to the etiological heterogeneity of autistic disorder and that a portion of cases of autism may actually be a result of homozygosity for the TS gene. In addition, the presence of affective disorders and autistic‐like syndromes or mild disturbances of social relatedness in some of the pedigrees suggests the hypothesis that TS may be responsible for a subgroup of families with cooccurring affective and autistic disorders and for some cases of familial aggregation of autism–PDD.
Clinical and genetic relationships between autism‐pervasive developmental disorder and Tourette syndrome: A study of 19 cases
Authors: Comings David E. , Comings Brenda G.
Published: June 2005

Children with autism or pervasive developmental disorder (PDD) and Tourette syndrome (TS) share a number of symptoms. Forty‐one cases have been reported in which PDD patients subsequently developed TS. We term this PDD→TS. We describe an additional 16 such patients plus 3 families where a close relative of a TS proband had autism. There was a high frequency of alcoholism, drug abuse, obsessive–compulsive, and other behavior disorders in the relatives of these patients. This frequency was virtually identical to that observed in relatives of individuals with TS only. We suggest there is an intimate genetic, neuropathologic relatedness between some cases of PDD and TS. Many observations have led us to suggest that the genetic defect in TS may be a mutation of tryptophan oxygenase and that TS is inherited as a semidominant semirecessive trait, i.e., homozygosity for a common gene which shows some expression in the heterozygous state. We propose that some types of PDD are inherited in the same fashion and by the same gene. This would explain the similarity of symptoms, frequent evolution of PDD into TS, the apparent recessive inheritance of PDD despite no increase in consanguinity, the high frequency of behavior problems in the relatives of PDD→TS patients and the serotonin abnormalities.
Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs
Authors: Heimler Audrey , Fox Joyce E. , Hershey Joel E. , Crespi Paul
Published: June 2005

A brother and sister born to normal, nonconsanguineous parents have a syndrome of profound sensorineural hearing deficiency, enamel hypoplasia limited to the permanent dentition, and nail abnormalities. This appears to be a previously unreported inherited syndrome.
Characterization of deletions at the retinoblastoma locus in patients with bilateral retinoblastoma
Authors: Kloss Kai , Währisch Petra , Greger Valerie , Messmer Elmar , Fritze Henning , Höpping Wolfgang , Passarge Eberhard , Horsthemke Bernhard
Published: June 2005

DNA samples from 92 unrelated patients with bilateral retinoblastoma were analyzed by Southern blot hybridization with cDNA and genomic clones of the retinoblastoma (RB‐1) gene. Qualitative and quantitative evaluation of the Southern blot patterns showed a deletion of all or part of the RB‐1 gene in 15 patients. Deletion hot spots were not detected. The study shows that 16% of germ cell mutations are detectable by Southern blot hybridization, but that densitometric analysis is required in most cases.
Interstitial deletion del(2)(q24q31) with a phenotype similar to del(2)(q31q33)
Authors: Wamsler Christine , Müller Bertram , Freyberger Gabriele , Schmid Michael
Published: June 2005

A 3 3/12‐year‐old girl with multiple anomalies is reported. An interstitial deletion del(2)(q24q31) was demonstrated. There is considerable overlap of symptoms in cases with del(2)(q31q33), which are reviewed.
Genetic analysis of Huntington disease in Italy
Authors: Ajmar F. , Mandich P. , Bellone E. , Abbruzzese G.
Published: June 2005

Twelve Italian families with Huntington disease were tested with 10 probes known to be linked to the disease locus and able to detect polymorphisms at the following loci on chromosome 4: D4S10, D4S127, D4S95, D4S43, D4S115, D4S111, D4S90. The results confirmed the applicability of the linkage approach for presymptomatic diagnosis in Italian families. Positive lod scores were found between D4S10, D4S95, D4S43 and the disease, wherease D4S90 did not indicate significant linkage values. With the limitations due to the small size of the tested sample, no genetic heterogeneity was detected in the families examined for loci D4S10, D4S95/S127, D4S43.
DiGeorge anomaly associated with 10p deletion
Authors: Monaco Giuseppe , Pignata Claudio , Rossi Elena , Mascellaro Ornella , Cocozza Sergio , Ciccimarra Filippo
Published: June 2005

DiGeorge anomaly (DGA) represents a heterogeneous entity, which is often sporadic, although familial cases and the association with monosomy 22q11 have been reported. Recently, a few patients with 10p deletion syndrome and immunological and other laboratory findings similar to DGA have been described. We report on an additional case of partial DGA associated with 10p deletion.
Family with 22‐derived marker chromosome and late‐onset dementia of the Alzheimer type: I. Application of a new model for estimation of the risk of disease associated with the marker
Authors: Percy Maire E. , Markovic Vjerica D. , McLachlan Donald R. Crapper , Berg Joseph M. , Hummel Jocelyn T. , Laing Marlene E. , Dearie Thomas G. , Andrews David F.
Published: June 2005

We have identified 2 sisters with probable dementia of the Alzheimer type who have an unusual 22‐derived marker chromosome with a greatly elongated short arm containing 2 well‐separated nucleolus organizer regions. A marker chromosome similar in appearance is uncommon in the general population. Eleven of 24 of their biological relatives were also found to have the marker. The known pedigree of this family encompasses 6 generations in 2 of which there is evidence of 10 cases of dementia of the Alzheimer type. The average age‐at‐onset of dementia is 65.8 ± 5.5 years; the average age‐at‐death among those apparently affected is 74.9 ± 8.3 years. A new model for the estimation of risk was applied to the family data. Persons in this family with the marker were found to be 4 times more likely to develop dementia than those without the marker, the 95% confidence interval for this risk being 1–50. The probability that the association of dementia and the marker is due to chance alone is.05 (1 in 20).
Postmortem chorionic villus sampling: Correlation of cytogenetic and ultrasound findings
Authors: Sorokin Yoram , Johnson Mark Paul , Uhlmann Wendy R. , Zador Ivan E. , Drugan Arie , Koppitch Frederick C. , Moody Joyce , Evans Mark I.
Published: June 2005

We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13‐month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 ± 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 ± 4.3 days) (P < .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation.
Molecular characterization of severe α‐Thalassemias causing hydrops fetalis in Taiwan
Authors: Ko Tsang‐Ming , Hsieh Fon‐Jou , Hsu Pi‐Mei , Lee Tzu‐Yao
Published: June 2005

α‐Thalassemia hydrops fetalis is a common disorder in Taiwan. The condition causes perinatal death and many maternal obstetrical complications. In order to determine the molecular defects of this condition in Chinese, 87 unrelated families with this disorder were collected in the past 4 years. The molecular defects were studied by Southern blotting and DNA hybridization with φζ1‐globin gene and LO (a 0.4 kb BamHI/EcoRI fragment in the 5′ flanking region of the ζ2‐globin gene) probes. Eighty‐one (93.1%) fetuses had homozygous Southeast Asian deletion (– –SEA/– –SEA). Five (5.7%) fetuses were compound heterozygotes for the Southeast Asian deletion and Thailand deletion (– –SEA/– –THAI). The remaining fetus was a compound heterozygote for the Southeast Asian deletion and an uncharacterized nondeletional defect (– –SEA/(αα)Th). The molecular defects of α‐thalassemia hydrops fetalis in Chinese are heterogeneous. This fact has important implications for genetic counseling and prenatal diagnosis.
Pseudo‐trisomy 13 syndrome
Authors: Cohen M. Michael , Gorlin Robert J.
Published: June 2005

We have coined the term “pseudo‐trisomy 13 syndrome” to designate cases of holoprosencephaly, severe facial anomalies, postaxial polydactyly, various other congenital defects, and normal chromosomes. Eleven instances are summarized. Two pairs of sibs and two other cases with consanguinity suggest autosomal recessive inheritance. Autosomal recessive inheritance is possible. Alternately, an undetected microdeletion and etiologic heterogeneity (some cases possibly representing dominant new mutations) must be considered. Further delineation is necessary. It is hoped that this paper will serve as a focus for further discussion of the problem.
Facio‐cardio‐renal (Eastman‐Bixler) syndrome
Authors: Nevin N. C. , Hill A. E. , Carson D. J.
Published: June 2005

We report on a 5‐year‐old boy with moderate mental retardation, horseshoe kidneys, tricuspid valve prolapse, and a characteristic face with broad nasal root, prominent ears, and a cleft palate. These manifestations suggested the diagnosis of the Eastman‐Bixler syndrome. Our patient also had an isolated growth hormone deficiency which responded successfully to treatment.
Crossed polydactyly type I in a mother and son: An autosomal dominant trait?
Authors: Ishikiriyama Satoshi , Sawada Hiroyuki , Nambu Haruo , Niikawa Norio
Published: June 2005

In a Japanese family, a propositus and his mother had crossed polydactyly type I. A maternal grandaunt also had preaxial polydactyly of the feet. The findings that both of the mother and son had the identical type of polydactyly are consistent with an autosomal dominant inheritance with variable expressivity. Other explanations include X‐linked recessive inheritance, polygenic inheritance, and a chance occurrence of the 2 different kinds of polydactyly.
Chromosome instability and X‐ray hypersensitivity in a microcephalic and growth‐retarded child
Authors: Barbi Gotthold , Scheres Jacques M. J. C. , Schindler Detlev , Taalman Rob D. F. M. , Rodens Klaus , Mehnert Karl , Müller Max , Seyschab Helga
Published: June 2005

We report on a microcephalic, growth‐retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short‐term lymphocyte cultures. Follow‐up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. We propose that our patient belongs to the expanding category of “AT‐related” genetic disorders, probably to the Nijmegen breakage syndrome.
46,XX gonadal dysgenesis with epibulbar dermoid
Authors: Quayle Sara A. , Copeland Kenneth C.
Published: June 2005

Pure gonadal dysgenesis with 46,XX genotype is a rare abnormality with unknown etiology. Although sensorineural deafness has been described with 46,XX gonadal dysgenesis, the majority of reported cases of 46,XX gonadal dysgenesis have no associated physical abnormalities. We report a patient with 46,XX gonadal dysgenesis associated with epibulbar dermoids and preauricular skin tags, the classic ocular and skin manifestations of Goldenhar sequence (oculoauricular vertebral dysplasia). We propose that our patient may represent a new and previously unreported syndrome.
Molecular analysis of a patient with neurofibromatosis 1 and achondroplasia
Authors: Pulst Stefan‐M. , Pribyl Thomas , Barker David F. , Riccardi Vincent M. , Ren Meina , Yaari Hana , Korenberg Julie R.
Published: June 2005

The gene for von Recklinghausen neurofibromatosis (NF1) is on proximal 17q; the location of the gene for achondroplasia (ACH) is unknown. We have begun a molecular analysis of a patient with mental retardation, NF1 and ACH, a clinical presentation suggestive of a contiguous gene syndrome. In addition, this individual has a 47,XYY chromosome constitution. To define a possible chromosome 17 deletion, we investigated the copy number of DNA sequences linked to NF1 with conventional and pulsed‐field gel electrophoresis (PFGE). We found no evidence for a deletion on chromosome 17. These results make it unlikely that this patient harbors a single deletion in the NF1 region causing both NF1 and ACH and suggest different mechanisms for the de novo occurrence of 2 autosomal dominant disorders in this individual.
Congenital lung herniation
Authors: Neilands Pamela S. , Kurczynski Thaddeus W. , Elshafie Mohammed A. F. , Uraizee Faheem
Published: June 2005

Congenital lung herniation is a rare condition. It is usually associated with a costal cartilage defect. We report on a newborn boy with a partial lung herniation through the parietal pleura and skin associated with a sternal malformation. We propose the herniation occurred around the fifth month of fetal life and interfered with sternal ossification.
Joubert syndrome: A clinical and pathological description of an affected male and a female fetus from the same sibship
Authors: van Dorp Dieuwke B. , Palan Alzbeta , Kwee Mei Lan , Barth Peter G. , van der Harten Johan J.
Published: June 2005

A severely retarded male child with Joubert syndrome is described. He had severe neurological anomalies including Dandy‐Walker malformation, hypoplasia of the corpus callosum, occipital meningo‐encephalocele, and bilateral coloboma of the optic nerve with retrobulbar cystic mass. This is the first male described so far with both coloboma and other midline defects. A detailed autopsy on an affected female fetus from the mother's second pregnancy is presented.
Father and two children with total anomalous pulmonary venous connection
Authors: Raisher Bradley D. , Dowton S. Bruce , Grant James W.
Published: June 2005

Total anomalous pulmonary venous connection (TAPVC) is a rare form of cyanotic congenital heart disease which, without surgical treatment, has a high mortality in the first year of life. Reports of familial recurrence of TAPVC have involved sibs, first cousins, and twins. This is the first report of TAPVC in a father and his 2 children. The implications for genetic counseling to families with this anomaly and individuals reaching adulthood after repair of TAPVC are considered.
Identification of the origin of centromeres in whole‐arm translocations using fluorescent in situ hybridization with α‐satellite DNA probes
Authors: Tharapel Avirachan T. , Qumsiyeh Mazin B. , Martens Paula R. , Tharapel Sugandhi A. , Dalton James D. , Ward Jewell C. , Wilroy R. Sid
Published: June 2005

We detected 2 patients with whole‐arm translocations resulting in a derivative chromosome consisting of 18q and 21q. Because the breakpoints were near the centromere, classical cytogenetic techniques could not determine the centromeric origin of the derivative chromosomes. Using nonradioactive in situ hybridization with a chromosome 18 α‐satellite DNA probe (D18Z1), the centromeres in the abnormal chromosomes were determined to be from chromosome 18. The abnormality in one patient resulted in monosomy 18p with a karyotype 45, XX, −18, −21, + der(18)t(18;21) (p11;q11)mat complement. The second patient with a 46, XX, −21, + der(18)t(18;21)(p11;q11) de novo karyotype had complete trisomy of 18q. In both cases the appropriate phenotype was observed.
Hyperekplexia: Pedigree studies in two families
Authors: Hayashi Takashi , Tachibana Hidetoshi , Kajii Tadashi
Published: June 2005

We report on 2 unrelated Japanese families, each with several individuals affected with hyperekplexia, a rare autosomal dominant form of exaggerated startle response of neonatal onset. In the first family, affected relatives included a 4‐week‐old boy, his mother, grandmother, a maternal uncle, and 2 maternal cousins. In the second family, affected were a 4‐week‐old boy, his father, and an elder brother. These 9 individuals had various combinations of transient infantile hypertonia and hypokinesia, exaggerated startle response with falling episodes, nocturnal myoclonus and an easily elicited head retraction reflex, hip dislocation, and umbilical hernia. Treatment with clonazepam was effective in relieving these manifestations in the affected infants and children.

Genetic analysis of these 2 families and 4 others in the literature suggests autosomal dominant inheritance with considerable variability but complete penetrance. Another 3 families in the literature were reported, suggesting the existence of startle disorder with an autosomal recessive inheritance. A sporadic case is also known, presumably representing a fresh mutation of a dominantly inherited trait.
Syndactyly type IV/hexadactyly of feet associated with unilateral absence of the tibia
Authors: Rambaud‐Cousson Annie , Dudin Anwar A. , Zuaiter Ahmad S. , Thalji Amin
Published: June 2005

We report on a newborn girl with syndactyly type IV, hexadactyly of feet, and right tibial hemimelia. She has 5 other relatives with identical anomalies of the hands and feet transmitted as an autosomal dominant trait. Syndactyly type IV is rare as is absence of the tibia. We suggest the possibility that syndactyly type IV may be a more complex entity, including lower limb malformations, and transmitted as autosomal dominant with variable expressivity.
Familial posterior helical ear pits and Wiedemann‐Beckwith syndrome
Authors: Best Lyle G.
Published: June 2005

Multiple cases of posterior helical ear pits (PHEP) with apparent autosomal dominant inheritance in a very large family are reported. There are at least 2 cases of Wiedemann‐Beckwith syndrome (WBS) within this family. Three other instances of familial PHEP and/or WBS are presented. An individual with a somewhat atypical osteopetrosis and PHEP is described. The previous literature of PHEP and the association with WBS is reviewed.
Urofacial syndrome associated with hydrocephalus due to aqueductal stenosis
Authors: Teebi Ahmad S. , Hassoon Mohammed M.
Published: June 2005

The urofacial syndrome is an autosomal recessive disorder of distorted facial expression and neurogenic bladder with resultant urogenital tract damage. We report on an 8‐year‐old boy of consanguineous Arab parents with inverted facial expression upon laughing and renal changes as a consequence of a neurogenic bladder in addition to hydrocephalus due to stenosis of the aqueduct of Sylvius. We suggest that the association is not fortuitous and probably widens the spectrum of urofacial syndrome or represents a distinct entity mimicking the urofacial syndrome.
Relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type I
Authors: Bale Sherri J. , Amos Christopher I. , Parry Dilys M. , Bale Allen E.
Published: June 2005

Occipitofrontal circumference (OFC) was strongly correlated with height in 72 normal Caucasian men (r = 0.28, P = 0.018) and 78 women (r = 0.53, P < 0.0001). OFC : height ratios were approximately normally distributed in each sex with a mean of 0.326 (standard deviation [sd] = 0.0139) in males and 0.335 (sd = 0.0177) in females. Relative macrocephaly (an OFC greater than the 95th centile for height) was seen in seven ofnine probands with the nevoid basal cell carcinoma syndrome (NBCC), eight of 32 non‐probands with NBCC, three of four neurofibromatosis type 1 (NF1) probands, and six of nine non‐probands with NF1. Thirty‐one percent of the non‐proband NBCC cases had OFC less than the 50th centile for height, while none of the NF1 cases had this finding. Head size appears to be related to proband status in NBCC, while the evidence suggests that NF1 is a true macrocephaly syndrome. Objective detection of relative abnormalities in head size may aid in syndrome delineation and diagnosis.
Animal model: Chromosomal fragile site expression in dogs: I. Breed specific differences
Authors: Stone Diana M. , Jacky Peter B. , Hancock Dale D. , Prieur David J.
Published: June 2005

Peripheral blood lymphocytes from clinically normal Doberman pinscher and boxer dogs were cultured for folate‐sensitive and, in preliminary studies, aphidicolin‐inducible fragile site expression. Both autosomal and X chromosomal fragile sites were observed in canine cells cultured under folate/thymidine depletion and in cells cultured in medium containing aphidicolin. Results from the three dogs evaluated for both folate‐sensitive and aphidicolin‐inducible fragile site expression showed that the frequency of fragile site expression was significantly (P < 0.05) greater in cells cultured in medium containing aphidicolin than in cells cultured in folate/thymidine‐depleted medium. Cells from the boxer dog expressed a high percentage (66.67%) of aphidicolin‐inducible fragile sites in contrast to the Doberman pinscher dog in which only 21.10% of the lymphocytes expressed aphidicolin‐inducible fragile sites. The frequencies of spontaneous and folatesensitive fragile site expression did not vary significantly by breed of dog. Age of dog was significantly and positively correlated with frequency of folate‐sensitive fragile site expression in dogs of the boxer breed, but not in dogs of the Doberman pinscher breed. The dog X chromosome expressed three folatesensitive and aphidicolin‐inducible fragile sites. The G‐band location of these three fragile sites showed homology with three recognized constitutive common fragile sites on the human X chromosome: Xp22, Xq21, and Xq27.2. Two specific autosomal fragile sites were identified, one on the distal end of the long arm of chromosome 1 and one on the distal end of the long arm of chromosome 8. Other autosomal fragile sites were also apparent but could not be assigned reliably to specific chromosomes.
Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: Confirmation of the Hennekam syndrome
Authors: Gabrielli Orazio , Catassi Carlo , Carlucci Antonio , Coppa Giovanni V. , Giorgi Pierluigi
Published: June 2005

We report on a male with intestinal lymphangiectasia, mild mental retardation, seizures, and a typical face; the syndrome was first delineated by Hennekam et al., Am. J. Med. Genet. 34:593‐600 [1989]. His parents are consanguineous. This case seems to confirm the existence of the Hennekam syndrome.
Immunoglobulin class and subclass deficiencies prior to Epstein‐Barr virus infection in males with X‐linked lymphoproliferative disease
Authors: Grierson Helen L. , Skare James , Hawk John , Pauza Mary , Purtilo David T.
Published: June 2005

Patients with X‐linked lymphoproliferative (XLP) disease are characterized by extreme vulnerability to Epstein‐Barr virus (EBV). Following infection with EBV, affected males develop fatal infectious mononucleosis (IM), hypogammaglobulinemia (H), or non‐Hodgkin's lymphoma (NHL). In addition, hyper IgM, red cell aplasia, necrotizing lymphoid vasculitis (NLV), and aplastic anemia occur rarely. The recent use of DNA restriction fragment length polymorphism (RFLP) probes in linkage with the XLP gene now permit detection of affected males prior to primary EBV infection. We have measured immunoglobulin class and subclass levels in sera from EBV‐negative males who were either positive or negative for the XLP genotype by RFLP analysis. Elevated IgA or IgM and/or variable deficiency of IgG, IgG1, and IgG3 occurred in the sera of 13/13 RFLP‐positive, EBV‐negative males. No consistent abnormalities were noted in 14 RFLP‐negative, EBV‐negative males. We conclude that the immune defect in XLP is not solely EBV‐specific, although EBV is responsible for most of the morbidity and all of the mortality. Further, serial measurement of Ig levels may provide information regarding status of EBV‐negative males at risk where RFLP analysis is uninformative or in families where sporadic cases of fatal IM, acquired hypogammaglobulinemia or NHL have occurred, but wherein the genotype of XLP cannot be documented.
Characteristics of the postcounseling reproductive decision‐making process: An explorative study
Authors: Frets Petra G. , Verhage Frans , Niermeijer Martinus F.
Published: June 2005

An in‐depth, recorded interview of 30 couples 2–3 years after genetic counseling explored the characteristics of the postcounseling decision‐making process, including the role of guilt feelings towards the proband. The study concerned couples with an affected child, sib, or spouse. Results were evaluated by 2 to 4 judges. In contrast to other studies, a generally unstructured decision‐making process was found whereby guilt feelings played a significant role in more than half the couples. Guilt feelings were more predominant in couples with an affected sib than in those with an affected spouse. Lack of structure did not seem to complicate the decision‐making process. Therefore, authors do not advocate promotion of structuring the decision‐making process. Genetic counselors might focus on understanding counselees' feelings concerning the reproductive decision. Acceptance of apparently irrational considerations is particularly important, because these feelings indicate the influence of unconscious motives. Another important aspect of supporting counselees is to understand the role played by guilt feelings toward parents or an affected sib.
Animal models: Prenatal diagnosis of Chediak‐Higashi syndrome in the cat by evaluation of cultured chorionic cells
Authors: Kahraman M. Müfit , Prieur David J.
Published: June 2005

The autosomal recessive disease Chediak‐Higashi syndrome (CHS) is a progressive and generally fatal disease of humans. The under lying genetic defect in CHS is unknown and prenatal diagnostic methods have not been applied to this disease. The purpose of this study was to determine if CHS chorionic cells expressed a characteristic of CHS—enlarged lysosomes—that would permit the prenatal diagnosis of the disease. Cats with CHS, which have been shown to be homologous with human CHS, were used as the model system in this study. Chorionic tissue samples were obtained from CHS and control cat fetuses and cultures of cells were established. Acid phosphatase was utilized as a marker of lysosomes and cultures of chorionic fibroblasts from CHS and control fetuses were stained histochemically for acid phosphatase. The diameter of the largest lysosomes in 150 cells of each fetus was determined. The mean (±SD) diameter (in μm) of the largest lysosomes of normal fetuses was 0.9 ± 0.13 (range 0.5–7.0 μm), whereas the mean diameter of lysosomes in CHS chorionic cells was 3.9 ± 0.65 μm (range 0.5–25 μm). These means were significantly different (P < 0.0001). These data suggest that it should be possible to diagnose human CHS in the first trimester by chorionic villus sampling.
Adams‐Oliver syndrome revisited
Authors: Whitley Chester B. , Gorlin Robert J.
Published: June 2005

The occurrence of Adams‐Oliver syndrome in a patient from the same geographic area as the first reported kindred led to follow‐up of the original family, and to a survey of the literature. Of 81 cases in 32 families, there is an approximately equal distribution between sexes (38 males: 43 females). Vertical transmission in at least 8 families is consistent with autosomal dominant inheritance. The phenotype is variable with a range of mild‐to‐severe defects of the scalp and/or underlying bone. Despite large defects of the cranium, central nervous system abnormalities have not been found and intellectual development appears to be normal. Limb defects are usually limited to the digits, but may involve the long bones and are entirely absent in some obligate carriers of the gene. Cutis marmorata and tortuous, dilated scalp veins have been reported in association with the major head and limb defects, but also in isolation as a forme fruste phenotype. Thus, there is a broad range of variable expression ranging from cases with lethally hemorrhagic cranial defects and/or severe limb malformations, to patients without any apparent manifestations. Despite a phenotypic resemblance to isolated aplasia cutis congenita and to the syndrome of terminal transverse limb defects, Adams‐Oliver syndrome appears to be causally distinct. While the underlying pathophysiologic mechanism remains unknown, it can be speculated that cranial vertex defects and malformations of the limbs represent field defects resulting from impaired circulation in “watershed” areas during a critical period of development.
Variable expression of vision in sibs with albinism
Authors: Summers C. Gail , Creel Donnell , Townsend Dewayne , King Richard A.
Published: June 2005

Oculocutaneous albinism is defined by the presence of cutaneous and ocular hypopigmentation, the latter associated with nystagmus, iris transillumination, reduced retinal pigment, foveal hypoplasia, and misrouting of the optic fibers at the chiasm. The visual acuity is variable but almost always reduced. We report on two brothers with oculocutaneous albinism and markedly different visual acuity. One brother has a visual acuity of 20/100, while the second has similar cutaneous pigmentation and visual acuity of 20/20 and had not previously been recognized as having oculocutaneous albinism. Both brothers have foveal hypoplasia and misrouting of the optic fibers at the chiasm. Biochemical analysis suggests that this is a tyrosinase‐related type of oculocutaneous albinism, This study demonstrates that careful observation of foveal development in relatives with normal vision is necessary to detect all individuals with albinism in a family. A suspected diagnosis of albinism may be confirmed when the visual‐evoked potentials show excessive decussation of the optic fibers at the chiasm.
Frontofacionasal dysplasia
Authors: White Evelyn W. , Figueroa Ramon , Flannery David B.
Published: June 2005

We report on the fourth case of frontofacionasal dysplasia and discuss the differential diagnosis of this autosomal recessive disorder.
Specification of small distal 6q deletions in two patients by gene dosage and in situ hybridization study of plasminogen and α‐L‐fucosidase 2
Authors: Narahara Kouji , Tsuji Kazushiro , Yokoyama Yuji , Namba Hiroshi , Murakami Masae , Matsubara Tsunenori , Kasai Ryozo , Fukushima Yoshimitsu , Seki Takashi , Wakui Keiko , Seino Yoshiki
Published: June 2005

Gene‐dosage and in situ hybridization study of plasminogen (PLG) and α‐L‐fucosidase 2 (FUCA2) was performed on two patients with a small deletion of the distal long arm of chromosome 6, to define the structural abnormality more precisely. The results led to the cytogenetic diagnosis of an interstitial 6q deletion, del(6)(q25.1q25.3), in one patient and of a terminal 6q deletion resulting from a paternal t(1;6)(q44;q2605) translocation in the other patient. The latter patient had congenital noncommunicating hydrocephalus due to obstruction at the level of the foramen of Monro or the third ventricle which has not previously been described in terminal 6q deletions. Review of the literature suggests the emergence of a clinical syndrome associated with terminal 6q deletions.