bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetralogy of Fallot with pulmonary atresia in siblings
Authors: Der Kaloustian Vazken M. , Ratl Habib , Malouf Joe , Hatem Joe , Slim Michel , Tomeh Antoine , Khouri Joseph , Kutayli Farid , Opitz John M. , Reynolds James F.
Published: June 2005

We present two sisters with tetralogy of Fallot and pulmonary valve atresia. Both had identical anatomical findings as seen at cardiac catheterization and angiography and verified operatively, with, in particular, identical bronchial circulation and pulmonary valve structure. The parents are first cousins and there is no history of other affected relatives. We suggest that this is a specific, recessively inherited type of tetralogy of Fallot.
Ectopia cordis and cleft sternum: Evidence for mechanical teratogenesis following rupture of the chorion or yolk sac
Authors: Kaplan Lawrence C. , Matsuoka Rumiko , Gilbert Enid F. , Opitz John M. , Kurnit David M. , Reynolds James F.
Published: June 2005

We present case material and a literature survey to document the association between ectopia cordis and band disruption anomalies. The occurrence of thoracic ectopia cordis with a cephalic‐pointing cardiac apex suggests an arrest of cardiac descent at 3 weeks of development, consistent with our finding of ectopia cordis in a 28‐day human embryo. Mechanical compression secondary to rupture of the chorion and/or yolk sac at 3 weeks of gestation would interfere with normal cardiac descent and compress the chest, yielding thoracic and pulmonary hypoplasia. Congenital heart defects associated with ectopia cordis may represent deformations secondary to mechanical distortion of the developing heart following early rupture of the chorion and/or yolk sac. As is illustrated by our clinical specimens, tethering of the heart to periumbilical structures by bands could yield thoracoabdominal ectopia cordis. The milder anomaly of cleft sternum, which is also associated with band disruptions, may occur later in development following rupture of the chorion, yolk sac, or amnion.
Deoxyuridine increases folate‐sensitive fragile site expression in human lymphocytes
Authors: Reidy John A. , Reynolds James F.
Published: June 2005

Deoxyuridine (dU) increases chromosome breakage at folic acid (FA)‐sensitive common fragile sites (mostly 3pl4 and 16q23) in human lymphocytes. This dU‐related increase can be suppressed by thymidine or FA. These results suggest that the mechanism of fragile site expression in low FA medium involves misincorporation of dU into DNA.
Chromosomal polymorphisms of 1, 9, 16, and Y in 4 major ethnic groups: A large prenatal study
Authors: Hsu Lillian Y. F. , Benn Peter A. , Tannenbaum Hody L. , Perlis Theresa E. , Carlson Ann D. , Opitz John M. , Reynolds James F.
Published: June 2005

Using trypsin Gicmsa banding (GTG), major polymorphisms of the constitutive heterochromatin regions of chromosome 1, 9, 16, and Y were recorded in a New York City population. Polymorphisms were recorded from amniotic fluid specimens received from 6,250 patients from 4 major population groups, ic. White (European)–2,334 cases, American Black–1,795 cases, Hispanic descent–1,737 cases, and Asian (Oriental and Indian)–384 cases.

The major chromosomal polymorphisms were classified as follows: obvious pericentric inversion of the constitutive heterochromatin of the long arm of the chromosome (inv qh); significantly enlarged heterochromatic region of the long arm (qh+ is greater than, or equal to, twice the size of the short arm of chromosome 16 [16p]); very small or deficient heterochromatic region in the long arm (qh−); large Y (Yq‐f > size of chromosome 18), small Y (Yq− < size of a G‐group chromosome), and pericentric inversion of Y. Our prenatal study con‐firmed that the incidence of specific chromosomal variants is different in each population group. The most striking examples of this are the pcricentric inversion of chromosome 9 and the different polymorphisms of the Y chromosome. The incidence of inv (9) is highest in the Black population (3.57%); slightly above average in Hispanics (2.42%); and relatively low in Whites (0.73%) and Asians (0.26%). The Y appears to be more variable in Asian (3.37%) and Hispanic (1.82%) than in White or Black groups. The 9qh+ is seen more frequently than lqh +, or 16qh+. Inv (1), 9qh−, and 16qh− are rare. There were no cases of either Iqh− or inv (16). Thus far, we are not aware of any deleterious phenotypic nor clinical effect of these chromosomal polymorphisms nor of any apparent association with fetal wastage.
Multiple congenital anomalies syndrome with myopathy in chromosome 16 abnormality
Authors: Ionasescu Victor , Patil Shivanand , Hart Michel , Rhead William , Smith Wilbur , Opitz John M. , Reynolds James F.
Published: June 2005

An abnormality of chromosome 16 in an eight year‐old male was associated with a multiple congenital anomalies syndrome characterized by myopathy, cataracts, blepharophimosis, microcephaly, failure to grow, profound mental retardation, moderate sensorineural hearing loss, grand mal seizures, bilateral inguinal hernia, and thoracolumbar kyphoscoliosis. Magnetic resonance imaging of the head demonstrated absence of the corpus callosum and extensive loss of brain parenchyma in the occipital regions. Chromosome analysis from peripheral blood of the patient showed a rccombinant chromosome 16 [46, XY, rec (16), dup (p13.1 → p13.3) del (q22 → q24)]. The mother had a pericentric inversion of chromosome 16 [46, XX, inv(16) (p13.1;q22)]. Independent recombinant DNA studies have shown that the breakpoints of these chromosomal rearrangements flank the α‐globin gene cluster locus.
Lip pits and deletion 1q32 → 41
Authors: Bocian M. , Walker A. P. , Opitz John M. , Reynolds James F.
Published: June 2005

A patient with an interstitial deletion of chromosome lq[del( 1q327 → 41)] was found to have, among other anomalies, congenital lower‐lip pits. Lip pits are rare and are found mainly in association with the van der Woude syndrome and the popliteal pterygium syndrome; we cannot find a report of their association with a chromo‐some anomaly. To our knowledge, interstitial deletion of the segment 1q32 → 41 has not been reported. This observation raises the possibility that the van der Woude syndrome may be due to a submicroscopic deletion of chromosome 1q.
An anthropometric study of 38 individuals with Prader‐Labhart‐Willi syndrome
Authors: Butler Merlin G. , Meaney F. John , Opitz John M. , Reynolds James F.
Published: June 2005

Weight, height, sitting height, and 24 other anthropometric variables (5 body circumferences, skinfolds at 7 sites, 4 head dimensions, and 8 hand and foot measurements) were obtained on 38 Prader‐Labhart‐Willi syndrome (PLWS) individuals (21 with apparent chromosome 15 deletions and 17 nondeletion cases) with an age range of 2 weeks to 38 1/2 years. More than half of these individuals were measured on more than one occasion. The measurements confirmed the presence of short stature, small hands and feet, obesity, and narrow bi‐frontal diameter in PLWS. No differences were found for the anthropometric measurements between the 2 chromosome subgroups. Inverse correlations were produced with linear measurements (eg, height, hand and foot lengths) and age, which indicated a deceleration of linear growth relative to normal individuals with increasing age.
Unilateral carpal bone deformity in mother and son
Authors: Krauss Celeste M. , Herman Thomas E. , Holmes Lewis B. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a mother and son with unilateral absence of most of the proximal carpal bones, dysplasia of the distal row of carpal bones, and deformity of the forearm. Although carpal bone dysplasia has been reported in several congenital or progressive disorders, unilateral involvement with lack of progression makes this a distinct entity.
Congenital heart defects in Sotos sequence
Authors: Kaneko Hiroshi , Tsukahara Masato , Tachibana Hidetoshi , Kurashige Hideki , Kuwano Akira , Kajii Tadashi , Opitz John M. , Reynolds James F.
Published: June 2005

Of 10 patients with typical Sotos sequence, 5 had various congenital heart defects. They included 2 patients with secundum atrial septal defect, and one patient each with patent ductus arteriosus with mitral valve regurgitation, tricuspid atresia plus pulmonary atresia and ventricular seplal defect. Increases of head circumference and weight gain were less accelerated in the patients with congenital heart defects than in those without heart defects, while growth in length was comparable between the 2 groups. In view of these findings, it is suggested that the rate of congenital heart defects in patients with Sotos sequence is much higher than that reported in the literature.
The GAPO syndrome
Authors: Manouvrier‐Hanu S. , Largilliere C. , Benalioua M. , Farriaux J.‐P. , Fontaine G. , Reynolds James F.
Published: June 2005

A new case of GAPO syndrome is described in a 4‐year‐old Algerian girl born of first‐cousin parents. This patient also‐had a right pyelic‐kidney stone and cerebral venous circulation anomalies inducing scalp vein expansion.
Cholesteryl ester storage disease: Pathologic changes in an affected fetus
Authors: Desai Panna K. , Astrin Kenneth H. , Thung Swan N. , Gordon Ronald E. , Short M. Priscilla , Coates Paul M. , Desnick Robert J. , Reynolds James F.
Published: June 2005

The prenatal diagnosis of cholesteryl ester storage disease, a rare autosomal recessive disorder, was made by demonstration of deficient lysosomal acid lipase activity in cultured amniocytes from an at‐risk fetus. The histochemical and ultrastructural changes in the affected fetus (at 17 gestational weeks) are described and compared to findings in liver and duodenal biopsy specimens from a 9‐year‐old homozygous female. Massive lysosomal cholesterol and lipid accumulation was demonstrated in fetal hepatocytes, adrenal cells and syncytiotrophoblasts. Of particular note was the observation of extensive necrosis in the fetal adrenal glands. Necrosis of the adrenals may precede the calcification observed in some patients with cholesteryl ester storage disease and in most patients with Wolman disease, an allelic variant due to lysosomal acid lipase deficiency. Fibrosis of the liver and lipid accumulation in macrophages in liver and duodenum, which were present in the 9‐year‐old homozygote, were not observed in the affected fetus, and therefore, may represent later manifestations of the disease.
Further linkage data on Norrie disease
Authors: Kivlin Jane D. , Sanborn George E. , Wright Eileen , Cannon Lisa , Carey John , Opitz John M. , Reynolds James F.
Published: June 2005

We obtained a LOD score of +1.61 using DNA marker L1.28 in 5 generations of a family with Norrie disease, raising the total LOD score to +5.42. There have been no recombinations between the 2 loci in any family to date, making the marker useful for genetic counseling.
Animal model: Genetic control of the survival of trisomic fetuses in mice: A preliminary report
Authors: Vekemans M. , Trasler T. , Prieur David J.
Published: June 2005

Using trisomy 19 produced experimentally in mice, we examined the genetic control of the survival of trisomic fetuses. Data are presented that show clearly that the prevalence of experimentally produced trisomy 19 in mice, observed on day 15 of gestation, is genetically influenced. There appeared to be an inverse relationship between strain differences in frequency of trisomy 19 fetuses and frequency of fetal loss, suggesting that the observed differences in prevalence of trisomy 19 fetuses resulted from differential survival of trisomic fetuses.
Familial risks of congenital heart defect assessed in a population‐based epidemiologic study
Authors: Boughman Joann A. , Berg Kate A. , Astemborski Jacqueline A. , Clark Edward B. , McCarter Robert J. , Rubin Judith D. , Ferencz Charlotte , Opitz John M. , Reynolds James F.
Published: June 2005

Congenital heart defects (CHD) represent a heterogeneous group of disorders caused by chromosome abnormalities, mendelian disorders, teratogenic expo‐sures, and unknown etiologic mechanisms. A large group of various isolated defects is presumably multifactorial in origin. Previous studies of familial risks for specific anatomic defects obtained from clinical series may include significant biases and obscured pathogenic relationships. In this population‐based study we analyzed all cases of CHD in infants and a control birth cohort in the Baltimore‐Washington area. The rates of CHD were defined for first‐degree relatives of cases with isolated defects, grouped by a pathogenic classification scheme. Pre‐currence risks were found to vary among the groups, and risks for flow lesions were higher than previously reported. The sibling precurrence risk for hypoplastic left heart syndrome (13.5%) was not significantly different from that expected for an autosomal recessive mechanism; the risks for different types of ventricular septal defects (VSD) varied among mechanistic groups. The results indicate that the additive multifactorial model does not adequately account for the risks in all forms of isolated CHD of unknown etiology.
Animal model: Ceroidosis (ceroid‐lipofuscinosis) in Australian Cattle dogs
Authors: Wood Philip A. , Sisk Dudley B. , Styer Eloise , Baker Henry J. , Prieur David J.
Published: June 2005

Ceroid‐lipofuscinosis is described in Austrialian Cattle dogs. Lesions included storage of ceroid‐lipofuscin in most tissues with characteristic ultrastructural inclusion body patterns in neurons and other cells. Dolichol concentration of the affected dog's brain was similar to those in age‐matched control dog brains. However, concentrations in brain, liver and kidneys were markedly higher than in a slightly younger dog. Biochemical data including lysosomal enzyme activities exclude other lysosomal storage diseases. The clinical and pathological features of this disorder resemble those of the juvenile Spielmeyer‐Vogt type of Batten disease in humans.
Alopecia‐anosmia‐deafness‐hypogonadism syndrome revisited: Report of a new case
Authors: Johnston Kathreen , Golabi Mahin , Hall Bryan , Ito Melanie , Grix Art , Reynolds James F.
Published: June 2005

Johnson et al [1983] reported on a large family with alopecia‐anosmia‐deafness‐hypogonadism syndrome. We report the detailed findings of an unrelated, affected individual and emphasize the presence of hypohidrosis in our case. Our case indicates that this syndrome is not a private syndrome.
BrDU‐Giemsa labeling studies of satellite associations in parents of children with trisomy 21 or 13
Authors: Gould Sandra Lee , Martin‐DeLeon Patricia A. , Reynolds James F.
Published: June 2005

Studies on satellite association (SA) in parents of trisomy 21 offspring have not provided meaningful comparisons of SA frequencies since the latter was not expressed as a function of cell division number. We have used BrDU‐labeling to compare SA frequencies in first and second division metaphases from lymphocytes of parents with either a trisomy 21 or trisomy 13 child and a control group. Parental origin of nondisjunction was determined in three of six families using quinacrine heteromorphisms. In the two cases of trisomy 13 determined, the errors occurred in maternal meiosis.

BrDU‐labeled metaphases were analyzed for SA frequency in four groups: (A) parents contributing the extra chromosome; (B) spouses of the parents in A; (C) parents (nine) in whom the origin of a trisomy 13 or 21 was unknown; and (D) healthy controls (five). The mean numbers of SAs/cell and of chromosomes/SA were not significantly different among the four groups for both first and second division cells. Sex and age showed no effect on SA frequency. There were significant decreases in mean numbers of SA/cell and chromosomes/SA in second‐division cells (chromatids differentially stained) compared with first‐division cells (chromatids undifferentiated). In second‐division cells, two‐chromosome SAs of all types showed random concordant and discordant alignment in each subject. The results from this BrDU‐labeling approach provide no evidence that either quantitative or qualitative parameters of SA are directly related to a tendency of nondisjunction. They also show that acrocentric nondisjunction occurs in the presence of random chromatid alignment in SAs.
Duplication 3p21→3pter and cyclopia
Authors: Kurtzman Daniel N. , Van Dyke Daniel L. , Rich Candace A. , Weiss Lester , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a patient with an interchromosomal duplication of 3p, from 3p21 to 3pter, which apparently arose de novo. The infant had multiple malformations including holoprosencephaly and cydopia. It is possible that duplication 3p has a generalized effect on the holoprosencephalon or the cleavage of the embryonic forebrain. Fibroblasts from the patient are available from the NIGMS Human Genetic Mutant Cell Repository (GM 7216).
Proteus syndrome: An expanded phenotype
Authors: Clark Robin Dawn , Donnai Dian , Rogers John , Cooper Jane , Baraitser Michael , Opitz John M. , Reynolds James F.
Published: June 2005

We report on 11 new cases of Proteus syndrome to illustrate the broad range of the phenotype in this hamartomatous dysplasia. The cardinal manifestations of this sporadic disorder are hemihypertrophy, macrodactyly, exostoses, scoliosis, cavernous hemangiomas, lipomas, linear sebaceous nevi, and deeply rugated soles of the feet. Intelligence is usually normal. The differential diagnosis includes Klippel‐Trenaunay‐Weber and partial lipodystrophy syndromes.
Applications of the pattern variability index (σz) to the quantification of dysmorphogenesis in the hand
Authors: Garn Stanley M. , Leonard William R. , Poznanski Andrew K. , Reynolds James F.
Published: June 2005

We have generated percentiles for the pattern variability index (σz) of the hand in 1,088 normal infants, children, and adults and have analyzed pattern variability indices for 820 individuals representing 50 congenital malformation syndromes with respect to the normal percentiles. The majority of the affected individuals exhibited elevated (σz) values for the hand, some vastly in excess of normal, while such syndromes as Down, Turner, and the Prader‐Willi syndrome were low rather than high in pattern variability of the hand.
Melnick‐needles syndrome in males
Authors: Krajewska‐Walasek M. , Winkielman J. , Gorlin R. J. , Reynolds James F.
Published: June 2005

Melnick‐Needles syndrome is an X‐linked dominant trait, lethal in males. There are three well‐documented lethal examples of the disorder in the offspring of affected females and three examples in males born to normal parents who represent new mutations.
Melnick‐needles syndrome in males: A lethal multiple congenital anomalies syndrome
Authors: Donnenfeld Alan E. , Conard Katrina A. , Roberts Nancy S. , Borns Patricia Flint , Zackai Elaine H. , Opitz John M. , Reynolds James F.
Published: June 2005

A male fetus with decreased calvarial mineralization and suspected omphalocele was identified prenatally in a woman with oligohydramnios and Melnick‐Needles syndrome (MNS). At autopsy, exophthaimos, prune belly sequence with urethal atresia and megacystis, tetralogy of Fallot, atrioventricular canal defect, and complete malrotation of the gut were identified. Mandibular hypoplasia and delicate, bowed, irregular, long bones and ribs with widening and deep cupping of the metaphyses were found radiographically. In addition, we review 3 previously reported cases of males with similar, lethal malformations, all born to mothers with MNS. It is our conclusion that these anomalies characterize the male MNS phenotype. A review of all reported viable individuals with MNS identified 2 distinct entities: a mild form found only in females, compatible with normal life expectancy in most cases and inherited in an X‐linked dominant male lethal or sex limited autosomal dominant pattern, and a different, more severe disorder, termed precocious osteodysplasty, found in both males and females and inherited as an autosomal recessive trait.
Microcephaly, micrognathia, and bird‐headed dwarfism: Prenatal diagnosis of a seckel‐like syndrome
Authors: Majoor‐Krakauer D. F. , Wladimiroff J. W. , Stewart P. A. , van de Harten J. J. , Niermeijer M. F. , Neri Giovanni , Reynolds James F.
Published: June 2005

Microcephaly, intrauterine growth retardation, a hellenic nose, and severe micrognathia were diagnosed as a form of bird‐headed dwarfism (Seckel‐like) syndrome in a female infant. In the subsequent pregnancy, monitored by serial ultrasound examinations, severe growth retardation was established at 17 and 20 weeks of pregnancy. The head circumference was disproportionately small in relation to the abdominal circumference and enabled the diagnosis of microcephaly. There was also extreme micrognathia. The pregnancy was terminated, and the diagnosis of a Seckel‐like syndrome of bird‐headed dwarfism was confirmed at autopsy of the male fetus. This variant of bird‐headed dwarfism has probably autosomal recessive inheritance.

Ultrasonic assessment of the facial area together with the measurements of fetal head and abdominal circumference are essential in the early prenatal diagnosis of this syndrome in pregnancies of reliably established duration.
Mandibulofacial dysostosis (Treacher Collins syndrome): A new proposal for its pathogenesis
Authors: Sulik Kathleen K. , Johnston Malcolm C. , Smiley Steven J. , Speight Harold S. , Jarvis Bennie E. , Opitz John M. , Reynolds James F.
Published: June 2005

Acute exposure to 400 mg/kg 13‐cis retinoic acid (13‐cis F U, isotretinoin, Accutane®) on the ninth day postfertilization in mice (a time that corresponds to the fourth week postfertilization in humans) results in malformations that characterize mandibulofacial dysostosis (MFD, Treacher Collins syndrome). Deficiencies in the infraorbital region and in the mandibular ramus and condyle, abnormalities of the secondary palate, and external ear malformations were observed. Light and scanning electron microscopic analyses of affected embryos illustrate that within 12 hours of maternal 13‐cis RA treatment, markedly excessive (possibly premature) cell death occurs in regions where some of the cells are normally destined to undergo programmed cell death. Previous studies with retinoids have shown that they labilize lysosomal membranes and expand and strengthen regions of programmed cell death. Of particular interest for this study was cell death occurring in the dorsal (proximal) aspects of the maxillary and mandibular prominences of the first visceral arch, the second visceral arch, and the first visceral cleft, areas that correspond to the locations of the first and second arch ectodermal (“ganglionic”) placodes and first closing membrane, respectively. The derivatives of this region are those that are severely affected in MFD. As described in previous reports from this laboratory, 13‐cis RA is known to interfere with neural crest cells, resulting in major craniofacial malformations. However, the exposure times involved were earlier than those described herein. It is hypothesized that effects on the first and second arch ectodermal placodal cells at a time following the release from the neural folds of neural crest cells into the developing cranial region are of great significance in the pathogenesis of MFD. This is in contrast to the prevailing hypothesis that these malformations are the direct result of a primary interference with neural crest cells.
Cytogenetic study in children chronically habituated to inhalation of volatile substances
Authors: Salamanca‐Gómez Fabio , Moreta Germania , Palma Virginia , Garcia Teresa , Navarrete Carmen , Caraza Carlos , Varela Raúl , Hiroishi Mikio , López Moisés , Hernández Silvia , Buentello Leonora , Opitz John M. , Reynolds James F.
Published: June 2005

Deliberate inhalation of volatile substances is a common and harmful phenomenon among young persons around the world. Clinical and cytogenetic studies were performed in 35 children (33 boys and 2 girls) chronically habituated to inhalation of volatile agents, with the aim to define whether this practice is associated with chromosome abnormalities and if so to what extent. A significant increase in the rate of chromosome abnormalities and in the frequency of sister chromatid exchanges (SCE) was found in sniffers over the values in controls (p < 0.001). Clinical, socioeconomic, and cytogenetic findings are discussed.
Chromosome 18 aneuploidy: Anatomical variations observed in cases of full and mosaic trisomy 18 and a case of deletion of the short arm of chromosome 18
Authors: Urban Bruce , Bersu Edward T. , Opitz John M. , Reynolds James F.
Published: June 2005

Cases of full and mosaic trisomy 18 and a body of an infant with the 18p‐syndrome were dissected in detail to compare the anatomical variations associated with these 3 chromosome imbalances involving autosome 18. The types and numbers of morphologic variations present in both the full and mosaic trisomy 18 bodies were similar to the types and numbers of variations seen in all other cases of full trisomy 18 that have been sudied by gross dissection. Apart from an atrial septal defect, the body of the infant with the 18p– imbalance showed only 2 striking defects: (1) deficiencies of the levator palpebrae superioris muscle of the upper eyelid, and (2) absence of the ligament of the head of the femur. The first variation provedes a morphologic basis to explain the ptosis which is observed frequently in effected individual. Absence of the ligament of the head of the femur may be a factor contributing to congenital dislocation of the hip, which is reported occasionally in affecte individual. In addition to providing more detailed information about the phenotype of individual aneuploidy syndromes, studies of cases of single autosomes may provide additional insights about the genotype/phenotype relationships of specific chromosome segmeents.
Partial androgen resistance due to a distinctive qualitative defect of the androgen receptor
Authors: Pinsky Leonard , Kaufman Morris , Levitsky Lynne L. , Reynolds James F.
Published: June 2005

Using whole genital skin fibroblasts, we have characterized a novel androgen receptor mutation in a family with partial androgen resistance. The proposita was born with bilateral labioscrotal folds and a single perineal urogenital orifice. Her similarly affected maternal aunt was raised as a female with the support of gonadectomy and vaginoplasty. The mutant androgen receptor has a normal maximum binding capacity (Bmax), but an increased apparent equilibrium dissociation constant (Kd) with 5α‐dihydrotestosterone (DHT) and 2 synthetic androgens, methyltrienolone (MT) and mibolerone (MB). Preformed mutant DHT‐receptor complexes dissociate (K) at a near‐normal rate, but their MT and MB counterparts dissociate twice as quickly as normal. The native free mutant receptor is not more thermolabile than normal, but its recently dissociated counterpart is. Prolonged incubation of the cells with each of the 3 androgens causes the mutant receptor to acquire a normal increment of increased androgen‐receptor activity. This androgen‐sensitive pattern of misbehavior of the present mutant receptor distinguishes it from those responsible for 3 other families with partial androgen resistance studied previously. These differences will help to identify structure‐function domains on the androgen receptor protein, particularly in conjunction with the use of DNA probes to analyze mutations at the X‐linked androgen receptor locus.
Phenotypic spectrum of 45,X/46,XY individuals
Authors: Rosenberg Carla , Frota‐Pessoa O. , Vianna‐Morgante Angela M. , Chu T. H. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on five patients with 45,X/46,XY mosaicism. In these subjects, as well as in 58 individuals from the literature with a similar chromosome constitution, we did not find a preponderance of 46,XY cells among patients showing ambiguous to abnormal male external genitalia when compared to those patients with slight or no virilization. However, the average frequency of 46,XY cells in blood in these mosaic individuals suggests that this sample includes mainly individuals whose mosaicism originated early in embryonic cell division. Those individuals whose mosaicism originated later are not significantly represented in this sample and would have higher frequencies of 46,XY cells. These individuals would be excluded from an intersex sample if they had well‐virilized genitalia. This ascertainment bias suggests that the degree of virilization depends on the frequency of 46,XY cells.
Urofacial (Ochoa) syndrome
Authors: Ochoa Bernardo , Gorlin Robert J. , Opitz John M. , Reynolds James F.
Published: June 2005

Between 1965 and 1986 we saw 36 children with enuresis and urinary tract infection in association with “inversion” of facial expression when laughing. Urologic work‐up of these patients disclosed characteristic findings of mild neuropathic bladder in all cases, with severe urinary tract damage in most of them. The clear association of distortion in facial expression and neuropathic bladder with resultant damage to the genitourinary tract should prompt urological evaluation of individuals with “inversion” of facial expression. About two thirds of the patients also had moderate to severe constipation. We suggest the term urofacial syndrome for this disorder. The occurrence of the disorder in multiple sibs, normal parents, increased parental consanguinity, and equal sex ratio indicate autosomal recessive inheritance.
Interstitial deletion of chromosome 2 (p23p25)
Authors: Penchaszadeh Victor B. , Dowling Patricia K. , Davis Jessica G. , Schmidt Rina , Wapnir Raul A. , Opitz John M. , Reynolds James F.
Published: June 2005

We report a patient with a de novo interstitial deletion of the short arm of chromosome 2 (p23p25). The patient had microcephaly with prominent forehead and occiput, narrow rectangular face, clinodactyly, failure to thrive, delayed psychomotor development, and seizures. Maternal serum α‐fetoprotein was undetectable at 18 weeks of gestation. Heterozygosity at the red cell acid phosphatase locus (SRO‐2p25) and normal levels of red cell malate dehydrogenase (SRO2p23) are findings consistent with the presence of genetic material from bands 2p25 and 2p23.
Clinical variability of partial duplication 1q: A clinical report and literature review
Authors: Rosenthal J. , Abeliovich D. , Carmi R. , Opitz John M. , Reynolds James F.
Published: June 2005

A female baby with multiple congenital malformations was born to a father previously known as a carrier of reciprocal translocation, t (l;18) (q25;pll). Her chromosome constitution was 46,XX,−18,derl8,t(l;l8)(q25;pll)pat, namely, partial duplication Iq25→qter. The main manifestations were: macrocephaly, hirsutism, camptodactyly, eye defects, lymphedema, and duodenal atresia. This patient illustrates the phenotype variability expected from such a large duplication of chromosome 1.
Individual variation and specific cognitive deficits in the fra(X) syndrome
Authors: Theobald Theresa M. , Hay David A. , Judge Cliff , Opitz John M.
Published: June 2005

Mental retardation has been associated with fra(X) but comprehensive psychological evaluation has rarely been applied to 2 major behavioral questions 1) the extent of individual variation in IQ among fra(X) males and the possibility of some fra(X) males being of normal IQ; and 2) whether there is a depression in general IQ or whether specific abilities are impaired. The problems of developing an effective battery of tests for assessing fra(X) are discussed.

These questions were examined in 54 individuals, comprising fra(X) males, their obligate carrier mothers and those sisters shown to have the fra(X). Among noninstitutionalised males nonverbal IQ as measured on a Block Design test ranged from 100 to 0, and vocabulary scores while generally higher, ranged from 79–33. The males scored low on a digit span memory task, while performance on a memory of objects task was adequate. Despite lower overall scores, a similar pattern and variability emerged in institutionalised males. Daughters were extremely variable in performance and the mothers performed much better, supporting the view that women who have children are a selected subset of fra(X) syndrome individuals.

The performance of one male is discussed in detail. His vocabulary and nonverbal IQ scores were normal, despite his having other specific cognitive deficits. The pattern of abilities and behavior seen in fra(X) may result in an overestimation of intelligence and underestimation of penetrance when based on clinical impressions rather than formal psychological assessment. The implications of this for molecular and for population genetic approaches to fra(X) are discussed.
A genetic follow‐up study of 64 patients with the Pierre Robin complex
Authors: Sheffield L. J. , Reiss J. A. , Strohm K. , Gilding M. , Opitz John M. , Reynolds James F.
Published: June 2005

A genetic follow‐up study has been performed of 64 infants who were diagnosed as having Pierre Robin complex over a 23‐year period in South Australia. Patients and their families were contacted, family history was obtained, and physical examinations were performed with an aim to detect heterogeneity and establish recurrence risks. In 16 deceased patients, detailed autopsy reports allowed the conclusion that 12 (70%) had an underlying syndrome. Twelve of the 47 living patients (26%) were diagnosed as having an underlying syndrome, the most common of which was Stickler syndrome (6 cases). In most cases separation of syndromic cases from the nonsyndromic cases was possible in the neonatal period. In the 34 patients without an underlying syndrome, study of pregnancy and birth details did not reveal any distinctive etiologic factors. There was no recurrence in sibs of this group of patients with nonsyndromic Pierre Robin complex.
Diprosopus with associated malformations: Report of two cases
Authors: Pavone Lorenzo , Camera Gianni , Grasso Sebastiano , Gambini Claudio , Barberis Mauro , Garaffo Salvo , Russo Sebastiano , Neri Giovanni
Published: June 2005

We report on two patients with craniofacial duplication and anencephaly. In addition to these anomalies, one patient showed vertebral fusion and diaphragmatic hernia, and the other one presented cheilognathopalatoschisis.
Neuroaxonal dystrophy presenting with neonatal dysmorphic features, early onset of peripheral gangrene, and a rapidly lethal course
Authors: Hunter Alasdair G. W. , Jimenez Carmencita L. , Carpenter Blair F. , MacDonald Ian , Opitz John M. , Reynolds James F.
Published: June 2005

Infantile neuroaxonal dystrophy (IND) is a well‐established autosomal recessive neurodegenerative disease. Clinical signs generally begin toward the end of the first or during the second year of life. We are aware of at least 4 cases of pre‐ or perinatal onset of this condition, and report here on 2 brothers who were affected at birth and had an unusual clinical course with onset of peripheral gangrene that progressed to autoamputation of digits. Both boys died in infancy with pathological changes compatible with IND. The somewhat different clinical course in these brothers leaves open the possibility that this is a variant of neuroaxonal dystrophy due to an X‐linked recessive mutation.
Uncombable hair (pili trianguli et Canaliculi): Evidence for dominant inheritance with complete penetrance based on scanning electron microscopy
Authors: Hebert Adelaide A. , Charrow Joel , Esterly Nancy B. , Fretzin David F. , Opitz John M. , Reynolds James F.
Published: June 2005

Uncombable or spun‐glass hair (pili trianguli et canaliculi) is an uncommon condition in which the hair is “unmanageable” and has a distinct appearance on scanning electron microscopy. The hair is usually grossly abnormal in infancy and childhood, but may become normal later in life. Although dominant inheritance ahas been observed, most cases have been sporadic. Both receissive and dominant transmission with incomplete penetrance have been sporadic. Both recessive and dominant transmission with incomplete penetrance have been suggested as modes of inheritance.

We report the occurrence of this condition in a young girl, her brother, and her father. Although the proposital and her brother had characterisstically uncombable hair, their father appeared normal and denied any history of hair abnormality. However, the characteristic hair morphology was observed on scanning electron microscopy in all 3 relatives, documenting dominnat transmission and complete penetrance of the gene in this family.
Decreased superoxide dismutase‐2 activity in a patient with ring chromosome 6
Authors: Yoshimitsu Kazunori , Nishi Yoshikazu , Kobayashi Yohnosuke , Yoshimura Osamu , Ohama Koso , Oguma Nobuo , Usui Tomofusa , Opitz John M. , Reynolds James F.
Published: June 2005

Manganese superoxide dismutase (SOD‐2) activity was measured in erythrocytes and leukocytes of a patient with ring chromosome 6. Compared to normal control individuals, SOD‐2 activity in leukocytes of the patient was lower, whereas cuprozinc SOD (SOD‐1) activity was normal. These findings suggest the cause of decreased enzyme activity is the effect of the ring form on production of the enzyme or inherent instability of ring chromosomes.
Limb body wall complex: I. Pathogenesis
Authors: Van Allen M. I. , Curry C. , Gallagher L. , Reynolds James F.
Published: June 2005

Twenty‐five fetuses with limb body wall complex (LBW complex) were evaluated. The diagnosis was based on two out of three of the following: exencephaly/ encephalocele with facial clefts; thoraco‐ and/or abdominoschisis; and limb defect. Ninety‐five percent (24/25) of the fetuses had associated internal structural de‐fects. In 72% (18/25) the internal defects have been recognized as being secondary to vascular disruption. Concordance was not found between the side and location of the body wall defect versus the limb, internal, and cranial defects. In 85% there was evidence for persistence of the extraembryonic coelom by examination of the placenta. In this same group (85%) there was persistence of the ectodermal‐amnion margin, with the amnion being continuous with the skin of the body wall defect. In 40% (10/25) there were tags and amniotic adhesions at other sites. There was no difference in the types or incidence of internal defects between those with and those without amniotic bands.

The abnormalities in this collection and experimental animal models support vascular disruption during 4‐6 weeks' gestation as an etiology for LBW complex. There is disruption and loss of existing tissues, persistence of embryonic structures, and secondary malformations. Persistence of the extraembryonic coelom may lead to the typical amniotic tags, ring constrictions, and adhesions seen in some specimens.
Plasma immunoreactive β‐melanocyte stimulating hormone (lipotro‐pin) levels in individuals with prader‐labhart‐willi syndrome
Authors: Butler Merlin G. , Jenkins Bonnie B. , Orth David N. , Reynolds James F. , Ledbetter David H.
Published: June 2005

Plasma immunoreactive β‐melanocyte‐stimulating hormone (β‐MSH) levels, which actually represent the combined concentrations of β‐lipotropin (β‐LPH) and γ‐LPH in normal individuals, were measured in 12 patients (6 males and 6 females with an average age of 16.8 years, range 4 months to 27 years) with the Prader‐Labhart‐Willi syndrome (PLWS). Five patients were previously identified with high‐resolution analysis as having the 15q chromosomal deletion, whereas 7 patients had normal chromosomes. Hypopigmentation was observed in all 5 patients with the 15q deletion. Of the 7 individuals with normal chromosomes, two were hypopigmented and 5 had normal pigmentation. Fasting (6 to 12 hours) plasma samples were analyzed for immunoreactive β‐MSH in the 12 PLWS individuals. Plasma immunoreactive β‐MSH (LPH) levels were within the normal range in all 12 individuals. There was no significant difference in the plasma immunoreactive β‐MSH concentrations between patients who did and did not have the chromosomal deletion or in those who were or were not hypopigmented. Thus, a decrease in circulating plasma immunoreactive β‐MSH (LPH) does not appear to be the cause of the hypopigmentation observed in some patients with PLWS.
A syndrome of mental retardation, short stature, hemolytic anemia, delayed puberty, and abnormal facial appearance: Similarities to a report of aldolase a deficiency
Authors: Hurst J. A. , Baraitser M. , Winter R. M. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a brother and sister with mental retardation, short stature, delayed puberty, spherocytic anemia, and an abnormal facial appearance. The similarities to a child with aldolase A deficiency are discussed.
Use of the G8 probe in predicting risk of Huntington disease
Authors: Maestri Nancy E. , Beaty Terri H. , Folstein Susan E. , Meyers Deborah A. , Opitz John M. , Reynolds James F.
Published: June 2005

Discovery of the linkage between the G8 probe and the gene for Huntington disease (HD) in families of varying ethnic origin, age‐of‐onset characteristics, and neurological symptomatology, makes it possible to use the G8 marker for presymptomatic testing of at‐risk individuals. Risk estimates for such situations were calculated, using the program LIPED, with different G8 haplotype frequencies, different age‐of‐onset distributions, and varying amounts of family information. In the presence of untyped relatives, the resulting risk estimates can be extremely sensitive to G8 haplotype frequencies, and the higher risk was seen in individuals carrying rare haplotypes. Including haplotype information on distant relatives can also lead to greater variation in risk estimates. Changing the age‐of‐onset distribution had only a minimal effect on estimated risks; the largest effect was seen when informative at‐risk sibs of the consultand were in their forties.
A professional partnership with genetic support groups
Authors: Black Rita Beck , Weiss Joan O. , Optiz John M. , Reynolds James F.
Published: June 2005

Voluntary, lay genetic support groups have become important providers of supportive, educational, and social services for clients and families who face genetic disorders. A survey of 88 persons representing genetic support groups confirms that these organizations are providing their members with information and assistance about not only the genetic aspects of the disorders but also problems of daily living. Respondents noted that professionals frequently refer patients to their groups and that many of the groups have professionals working directly with them as guest lecturers, consultants, and advisory board members. At least 20% cited a lack of genetic counseling services for members of their groups as a serious problem and called for greater sensitivity to emotional concerns in the timing and delivery of genetic counseling by professionals. Respondents called for greater collaboration between the voluntary organizations and professionals but underscored the unique benefits of empathy and support from one's peers.
Update on counseling the family with a first‐degree relative with a congenital heart defect
Authors: Nora James J. , Nora Audrey Hart , Optiz John M. , Reynolds James F.
Published: June 2005

Updated recurence risks figures are presented for genetic counseling of families with a congenital heart defect (CHD) in a first‐degree relative.

Substantial changes are recommended for counseling the family in which a parent has CHD. The risk is much greater if it is the mother rather than the father who has the heart defect. The updated figures for recurrence risks in sibs have been revised, but are not greatly changed. Our central tenet in counseling is to base risk projections on the genetic and teratogenic history in the individual family and pregnancy.
Paracentric inversion of Xq and ovarian dysfunction
Authors: Dar Hanna , Tal Joseph , Bar‐el Hanna , Halpern Isachar , Sharf Mordechai , Optiz John M. , Reynolds James F.
Published: June 2005

We report on a paracentric inversion X(q13 q24) in a 20‐year‐old woman with ovarian dysfunction. The findings add evidence on the role of breakpoints in Xq13 and Xq24 in causing ovarian dysfunction. A review of the published data on paracentric inversion of chromosome X is included.
Acrofacial dysostosis with postaxial limb deficiency
Authors: Fryns J. P. , Van den Berghe H. , Reynolds James F.
Published: June 2005

Here we report on an adult man with the postaxial acrofacial dysostosis syndrome, as delineated by Miller et al [1979]. In addition to facial changes strikingly similar to that of the Treacher‐Collins syndrome and a cleft soft and hard palate, symmetrical postaxial limb deficiencies with absence of the fifth digital rays in both the upper and lower limbs were present.
Localization of the gene for X‐linked nephrogenic diabetes insipidus to Xq28
Authors: Kambouris Marios , Dlouhy Stephen R. , Trofatter James A. , Conneally P. Michael , Hodes M. E. , Optiz John M. , Reynolds James F.
Published: June 2005

X‐linked nephrogenic diabetes insipidus (NDI) was segregating in a large Indiana family. It was tested for linkage of the NDI gene to X‐chromosome molecular markers. Maximum lod scores of 3.15 and 3.01 (θ=0) obtained for the molecular markers F8A (F8C) and DXS15 (DX13) respectively, indicate that the NDI gene is located in Xq28. A lod score of 3.61 (θ=0) was obtained with multipoint linkage analysis of F8A and DXS15.
Congenital scalp skull defects with distal limb anomalies (Adams‐Oliver syndrome—McKusick 10030): Further suggestion of autosomal recessive inheritance
Authors: Koiffmann C. P. , Wajntal A. , Huyke B. J. , Castro R. M. , Optiz John M. , Reynolds James F.
Published: June 2005

We describe a man with manifestations of the Adams‐Oliver syndrome: congenital scalp defect with hypoplastic fingers and toes. The patient has normal first‐cousin parents: among seven sibs, three sisters and two brothers are normal; two brothers born with the same scalp lesion died as a consequence of bleeding from this abnormal area. There is no evidence of other affected relatives. The family of our patient is suggestive of autosomal recessive inheritance of this disorder with phenotypic manifestations identical to those present in the autosomal dominant form. Dermatoglyphic findings are discussed.
Scalp and limb defects with cutis marmorata telangiectatica congenita: Adams‐Oliver syndrome?
Authors: Toriello Helga V. , Graff Russel G. , Florentine Michael F. , Lacina Samuel , Moore W. David , Optiz John M. , Reynolds James F.
Published: June 2005

We report on a boy with congenital scalp and limb defects, consistent with a diagnosis of Adams‐Oliver syndrome (aplasia cutis congenita with terminal transverse limb defects). An additional finding present in this child and in his mother was cutis marmorata telangiectatica congenita. Although this boy fits the diagnostic criteria for Adams‐Oliver syndrome, his mother does not. We discuss whether this condition is highly variable, or heterogeneous.
Ichthyosis and neutral lipid storage disease
Authors: Musumeci Salvatore , D'Agata Alfonsina , Romano Corrado , Patané Rosario , Cutrona Domenico , Neri Giovanni , Reynolds James F.
Published: June 2005

A boy with a lipid storage disease characterized by lamellar ichthyosis, cataracts, hepatosplenomegaly, and leukocyte vacuoles has been identified in a Sicilian family. This patient shows all the characteristics of ichthyosis and neutral lipid storage disease (Chanarin‐Dorfman syndrome). Family data confirm an autosomal recessive inheritance; the heterozygotes may be detected by the presence of vacuoles in circulating eosinophils.