Familial testicular germ cell tumor: no associated syndromic pattern identified.

Background: Testicular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases.

Speech characteristics in the Kabuki syndrome.

Six children with Kabuki syndrome were studied to investigate speech patterns associated with the syndrome. Each child's speech was characterized with regard to articulation (types of errors and intelligibility), pitch (high or low), loudness (volume of speech), and prosody (general quality of speech that combines rate and inflection). All six children had a history of delayed speech and language acquisition and were receiving speech services.

A case-control study of nonsyndromic oral clefts in Maryland.

Purpose: Isolated, nonsyndromic oral clefts cases (n = 171) and unaffected controls (n = 182) were used to identify both genetic and environmental risk factors.

Methods: Infants born in Maryland between 1992 to 1998 with an isolated, nonsyndromic oral cleft [cleft lip (CL), cleft lip and palate (CLP), or cleft palate (CP)] were recruited and exposure plus family history data were collected. Controls were unaffected infants.

Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome.

In this study, we extend our examination of the function of the Prrx1 (a.k.a Mhox, Prx1, K-2, and Pmx1) as well as Prrx2 (a.

Third Prader-Willi syndrome phenotype due to maternal uniparental disomy 15 with mosaic trisomy 15.

We report on a boy with mosaicism for trisomy 15 and Prader-Willi syndrome (PWS) due to maternal isodisomy for chromosome 15. His phenotype is consistent with PWS and trisomy 15 mosaicism. Although our patient is unusual in having maternal isodisomy rather than the more common maternal heterodisomy, we think that his more severe PWS phenotype is due to his trisomy 15 mosaicism rather than to homozygosity for deleterious chromosome 15 genes.

OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects) in monozygotic twins.

The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is a consistent and recognizable pattern of midline abdominal and pelvic defects. It is rare, affecting 1 in 200,000 to 400,000 pregnancies and is even rarer in twin gestations. This is an autopsy study of OEIS complex in monozygotic twins after pregnancy termination at 20 weeks of gestation.

Molecular characterization of a unique patient with epimerase-deficiency galactosaemia.

Inherited deficiencies of UDP-galactose 4-epimerase (GALE) have been associated with two distinct phenotypes. The vast majority of North American patients are clinically asymptomatic, are identified through newborn screening programmes for classical galactosaemia, and are of African-American descent. At least two symptomatic patients have been reported, one Pakistani and the other Asian Muslim, both with severe complications in the neonatal period and subsequent mental retardation.

Antenatal diagnosis of lethal skeletal dysplasias.

Lethal skeletal dysplasias (LSD) are a heterogeneous group of rare but important genetic disorders characterized by abnormal growth and development of bone and cartilage. We describe the diagnosis and outcome of 29 cases of lethal skeletal dysplasias evaluated between January 1989 and December 1996 at the University of Maryland Medical Center and the Ultrasound Institute of Baltimore. Two cases presented at delivery with no prenatal care while the remaining 27 cases were identified by antenatal sonography.

Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992-1996.

Objective: Infants born in Maryland between June 1992 and June 1996 were used in a case-control study of nonsyndromic oral clefts to test for effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects.

Design And Setting: Cases were infants with an oral cleft ascertained through three comprehensive treatment centers, with additional ascertainment through a registry of birth defects maintained by the Maryland Health Department. Controls were healthy infants.

No evidence of linkage for cleft lip with or without cleft palate to a marker near the transforming growth factor alpha locus in two populations.

Nonsyndromic cleft lip with or without cleft palate is a common birth defect, affecting approximately 1 in 1,000 Caucasian newborns. Thirty-five multiplex families from the mid-Atlantic region of the United States and 22 families from central Mexico with a nonsyndromic form of cleft lip with or without cleft palate were selected for a linkage analysis. A tetranucleotide repeat marker (D2S443) located on the same yeast artificial chromosome as the transforming growth factor alpha locus was tested for linkage to a putative susceptibility Mendelian locus under varying levels of pentrance.

Evidence for an association between markers on chromosome 19q and non-syndromic cleft lip with or without cleft palate in two groups of multiplex families.

It has been reported that BCL3 on chromosome 19q, or a nearby gene, may play a role in the etiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) in some families. We tested 30 USA and 11 Mexican multiplex NSCL/P families for four markers on chromosome 19q: D19S178, APOC2/AC1, APOC2/007, and BCL3. While likelihood-based linkage analysis failed to show significant evidence of linkage, the transmission disequilibrium test indicated highly significant deviation from independent assortment of allele 3 at the BCL3 marker in both data sets (USA:P = 0.

Familial DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2: report of five families with a review of the literature.

The DiGeorge (DG), velocardiofacial (VCF), and conotruncal anomaly-face (CTAF) syndromes were originally described as distinct disorders, although overlapping phenotypes have been recognized. It is now clear that all three syndromes result from apparently similar or identical 22q11.2 deletions, suggesting that they represent phenotypic variability of a single genetic syndrome.

Confirmation of the Catania brachydactylous type of acrofacial dysostosis: report of a second family.

The acrofacial dysostoses (AFD) are a heterogeneous group of disorders combining varying severities of mandibulofacial dysostosis (MFD) with pre- and/or postaxial limb abnormalities. In 1993, Opitz et al. [Am J Med Genet 47:660-678] described a new AFD with mental retardation in a Sicilian mother and her four sons characterized by intrauterine growth retardation (IUGR), postnatal short stature, microcephaly, widow's peak, MFD without cleft palate, mild pre- and postaxial limb hypoplasia with brachydactyly, mild interdigital webbing, and cryptorchidism and hypospadias in males.

Complex chromosomal rearrangements: some breakpoints may have cellular adaptive significance.

Cytogenetic study of a 3-year-old girl with developmental delay and some minor abnormalities revealed a complex chromosome rearrangement (CCR) involving seven chromosomes with eight breakpoints, leading to monosomy of segment 5q15-q22. According to breakpoint distribution, CCRs may be classified as those with primary intrachromosomal abnormalities (including inversions, insertions, duplications, etc.) and those without them.

Gorlin syndrome (naevoid basal cell carcinoma syndrome): prenatal detection in a fetus with macrocephaly and ventriculomegaly.

The Gorlin (naevoid basal cell carcinoma) syndrome is an autosomal dominant disorder consisting principally of naevoid basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities, and intracranial calcification. We report the prenatal detection of the Gorlin syndrome by ultrasonography in a fetus with macrocephaly and mild ventriculomegaly.

Alpha 1-antitrypsin deficiency. Impact of genetic discovery on medicine and society.

An increasing body of molecular information resulting from advances in basic research is being incorporated into clinical practice by medical genetics. The process by which these research advances progress from the laboratory to the bedside and their medical, social, and legal impact is a topic of intense current interest. Some authors have claimed that new genetic information may lead to discrimination in insurance and employment; change the way courts allocate responsibility for injury and resultant damages; and be inappropriately interpreted by the medical profession.

The acrocallosal syndrome: expansion of the phenotypic spectrum.

A family demonstrating the acrocallosal syndrome in a female proband whose sister had anencephaly is described. Two similar cases were found in the literature (Gelman-Kohan et al., 1991; Cataltepe and Tuncbilek, 1992).

Phenotypic variability of del(2) (q22-q23): report of a case with a review of the literature.

An interstitial deletion of 2q22-q23 was found in a 2.5 year old boy with multiple congenital abnormalities (including Hirschsprung's disease) and severe mental retardation. Comparison with seven additional cases of 2q deletions from the literature does not allow the delineation of a clinically recognizable syndrome.

The McKusick-Kaufman syndrome: phenotypic variation observed in familial cases as a clue for the evaluation of sporadic cases.

The characteristic clinical picture of the McKusick-Kaufman syndrome was observed in a girl of Belorussian background. A supernumerary nipple was the only finding not previously described in reported familial cases of this syndrome. In general, the range of phenotypic variability should be the same in both familial and sporadic cases.