Intrauterine growth retardation associated with precocious puberty and sertoli cell hyperplasia.

The original description of patients with Russell-Silver syndrome included precocious puberty, the mechanism of which was unclear. We describe a child with a Russell-Silver syndrome-like phenotype who presented with precocious puberty that was associated with hyperplasia of the Sertoli cells. The patient was found to have an immature cryptorchid testicle; hyperplastic Sertoli cells were also aneuploid carrying trisomy 8. This chromosomal abnormality was present in Sertoli cells only and could not be detected in peripheral lymphocytes, tunica vaginalis, or other, normal, testicular tissue. Sertoli cells in culture showed excess aromatization providing an explanation for the rapid advancement of the patient's bone age. We conclude that in a patient with a Russell-Silver syndrome-like phenotype, Sertoli cell hyperplasia was associated with somatic trisomy 8, increased aromatization, and gonadotropin-independent precocious puberty.

Patient decisions regarding prenatal aneuploid fluorescence in situ hybridization results.

OBJECTIVE: To determine an appropriate risk cut-off to offer prenatal aneuploid FISH, and if FISH results affect patient decisions regarding pregnancy management. METHOD: Retrospective evaluation of 707 patients presenting for diagnostic prenatal testing. Studied parameters included gestational age, indication for testing, aneuploid risk, procedure performed, FISH (whether offered, requested, and/or performed), result turn-around time, karyotype results, decision after obtaining results, and the timing of that decision. Patients who were offered FISH were compared to those not offered FISH (student T-test). RESULTS: Twenty-five clinically significant abnormalities were detected by karyotype and/or FISH analysis. Thirteen out of 17 patients electing pregnancy interruption had FISH performed. There were no differences between the group that interrupted following FISH (n=7) and the group that interrupted following final karyotype results (n=6). Turn-around times for those abnormal samples with FISH testing was significantly shorter than for those without FISH testing (p=0.02). Risk thresholds of >or=0.5%, >or=1%, >or=2%, or >or=3%, would detect 92%, 84%, 48%, and 32% of the clinically significant anomalies with 663, 317, 118, and 66 FISH analyses performed, respectively. CONCLUSION: Acting on FISH results alone afforded a significantly shorter interval between test and pregnancy interruption. A risk cut-off >or=1% appears to optimize the detection rate and the yield of abnormal results.

Prenatal diagnosis of supernumerary ring chromosome 1: case report and review of the literature.

A supernumerary ring chromosome was found on amniocentesis performed for advanced maternal age. A review of the literature found 34 reports of supernumerary ring chromosome I which are compared to our case.

Establishment and cell cycle kinetics of a human squamous cell carcinoma in nude mice and in vitro.

A human squamous cell carcinoma of the virus was xenografted to athymic, nude mice. A tissue culture cell line designated SqCaVu-1H was derived from a second-passage xenograft. The growth characteristics and cell cycle kinetics in the xenografts and in SqCaVu-1H cells were compared. Approximately 80% of the tumor implants produced growing xenografts which had a 2-week latent period followed by Gompertzian growth with a doubling time of 5 to 30 days at 35 days postimplantation. The cell cycle kinetics of the xenografts revealed a heterogeneity from region to region within the tumor. G2 phase and S phase in the xenografts are approximately 8 and 13 hr, respectively. The SqCaVu-1H cells contain only human chromosomes. The modal chromosome number was 64. SqCaVu-1H cells produce plasminogen activator during logarithmic growth, and they produce tumors when injected s.c. into athymic, nude mice. Logarithmically growing SqCaVu-1H cells have a population-doubling time of 21.8 hr in tissue culture. In vitro, their cell cycle duration is approximately 16.0 hr, with G2 phase at 5.6 hr and S phase at 8.6 hr. Comparison of the growth of the same human tumor cells under in vivo and in vitro conditions serves to emphasize that tumor cell proliferation depends strongly on the microenvironment. The varied proliferation characteristics are correlated with their varied inhibition of deoxyuridine incorporation into DNA because of exposure to methotrexate. Logarithmically growing SqVaCu-1H cells had a 50% inhibitory dose of 2.2 X 10(-6) M. Plateau-phase cells in vitro had a 50% inhibitory dose of 9 X 10(-6) M, while the inhibition of cells from the xenografts was nearly dose independent.

Anisomastia associated with interstitial duplication of chromosome 16, mental retardation, obesity, dysmorphic facies, and digital anomalies: molecular mapping of a new syndrome by fluorescent in situ hybridization and microsatellites to 16q13 (D16S419-D16S503).

Anisomastia is a common problem among developing adolescent girls. We recently evaluated a 22-yr-old female patient who had severe anisomastia (which had been repaired by surgery), associated with moderate to severe mental retardation, a stocky body habitus with mild obesity, dysmorphic facies (prominent, upslanting palpebral fissures, beaked nose, and a prominent philtrum), webbed neck, low hairline, and severe bilateral clinodactyly of the third, fourth, and fifth fingers with acral (but not large joint) flexion contractures. A peripheral blood high resolution karyotype revealed additional chromosomal material within the long arm of chromosome 16. Densitometric analysis of amplified polymorphic sequence-tagged sites (STS) mapping to 16q suggested that the duplication is defined by the noninvolved markers D16S419 [16q12-cen, 66 centimorgan (cM) from 16p terminus] and D16S421 (16q13-q21, 84.4 cM), encompassing a maximum of 18.4 cM of genetic distance. The STS analysis showed that the duplication was on the maternally derived chromosome 16, resulting in two maternal (and one paternal) copies of that region of chromosome 16. The location was further confirmed by bacterial artificial chromosomes (BACs) that were obtained from a commercially available library, labeled, and used for fluorescence in situ hybridization. The BACs containing STSs D16S408, D16S3137, and D16S3032 (markers that correspond to 16q13) showed two regions of hybridization, indicating that these sites were duplicated, whereas a BAC containing the STS D16S512 (which corresponds to 16q21-q22) revealed one hybridization signal per 16q, indicating that the corresponding region was not involved in the duplication. The distance between the probe signals suggested a tandem duplication. We conclude that even though trisomy 16 is the most common autosomal trisomy in spontaneous abortions, few patients with unbalanced chromosome 16 abnormalities survive to adulthood; in this report we describe one such patient with an interstitial chromosome 16 duplication (at 16q13), who had a specific phenotype associated with abnormal breast size. There are clinical similarities between this patient and patients with other 16q abnormalities, although the breast findings were unique. Molecular cytogenetics, including fluorescence in situ hybridization and densitometric analysis of amplified STSs, provided useful tools for the precise mapping of the syndrome to 16q13, where the gene(s) responsible for this phenotype might be localized.

Serological detection of H-Y antigen in humans with a cellular radioimmunobinding assay and monoclonal antibody.

A sensitive and reliable serological assay for the detection of H-Y antigen is described which uses monoclonal H-Y antibody and a cellular radioimmunobinding assay on cultured human fibroblasts. Cell lines from 2 normal human females, 2 normal human males and one XX human male were tested in 3 separate assays. Cells from XY and XX males were found to contain H-Y antigen; however, the reaction against the XX male cells was found to be intermediate between the XY male and normal XX female cells.

Familial 10p trisomy resulting from a maternal pericentric inversion.

We report a familial recombination of a pericentric inversion of chromosome 10 resulting in 2 affected relatives who had 10p trisomy and 10q monosomy with the karyotypic abnormality designated rec(10) dup p,inv(10) (p11.2q26). Both of these individuals had the typical characteristics of 10p trisomy, however, at birth the proposita had mild facial anomalies suggesting that the distinct facial characteristics may be of postnatal onset in some cases. In addition, the proposita had gastroesophageal reflux causing severe anemia. The phenotype of our patients is compared to 41 patients with 10p trisomy reported in the literature.

Trisomy 7p resulting from 7p15;9p24 translocation: report of a new case and review of associated medical complications.

The authors report on a young girl with generalized developmental deficits originally thought to be caused by an unusual reaction to DPT vaccination. At the age of 4(1/2) years, chromosome analysis showed that the terminus of the short arm of chromosome 9 had extra material believed to originate from 7p terminus, thus she was considered to be trisomic for a segment of 7p and monosomic for a small portion of 9p [46,XX,der (9), t(7;9)(p15;p24)]. Ten years later, molecular cytogenetic testing using fluorescence in situ hybridization (FISH) confirmed that the extra chromosomal material represented partial trisomy 7p. The proposita had a high and large forehead, hypertelorism, and broad nasal bridge, findings seen in most individuals with trisomy 7p. Long-term follow-up showed the presence of hypothyroidism, obesity, and cerebral palsy. A review of all published cases of trisomy 7p with focus on associated complications suggests a well-defined pattern of abnormalities characterized by musculoskeletal, cardiovascular, neurological, genital, and ocular abnormalities in decreasing frequency. At least one-third of affected individuals died in infancy and close to half had severe mental retardation. FISH was essential in the confirmation of the cytogenetic abnormality and further delineation of the chromosomal disorder.

Interstitial deletion of 4p15.32p16.3 in a boy with minor anomalies, hearing loss, borderline intelligence, and oligodontia.

We describe an 11-year-old boy of Saudi origin with an interstitial deletion in the short arm of chromosome 4 (p15.32p16.3) as determined by G-banding and fluorescent in situ hybridization. His clinical manifestations were similar but not identical to previously reported cases of interstitial deletion in the same chromosomal region, and were not those associated with Wolf-Hirschhorn syndrome. The boy had normal facial characteristics, short stature, minor anomalies of hands and feet, amblyopia of the right eye, bilateral hearing loss, and hypotonia. On developmental testing, he had borderline intelligence, with a severe sensory integration and motor planning disorder, and severe deficits in the communication domain. In addition, he had severe oligodontia affecting his secondary dentition. This finding supports the presence of one or more genes involved in dentition in this chromosomal region.

De novo duplication of 17p [dup(17)(p12----p11.2)]: report of an additional case with confirmation of the cytogenetic, phenotypic, and developmental aspects.

We describe an apparent de novo duplication of bands 17p11.2 and p12. A comparison of the manifestations of a previously reported case with a similar karyotype [Magenis et al., Am J Med Genet 24:415-420 (1986)] and of our own case seems to indicate a characteristic pattern which includes prenatal and postnatal growth retardation, facial changes, club feet, and mild developmental deficits. The prominent facial changes are a relatively triangular face, downslanted palpebral fissures, malocclusion, and abnormal ears. In addition, this condition appears to be milder than other duplications of the short arm of chromosome 17, namely trisomy 17p and dup(17)(p11.2----cen).

[Doppler study in algodystrophy. Apropos of 10 cases]. / Le Doppler dans l'algodystrophie. A propos de 10 cas.

Algodystrophy is usually attributed to disorders of microcirculation, and one may reasonably expect to demonstrate these by the Doppler method applied to arteries. Ten patients with algodystrophy stage I were explored and compared with 10 healthy controls and 10 patients with diseases likely to encourage the development of algodystrophy. Systolic, diastolic and mean blood flow velocities were recorded at different levels in the limbs involved and compared with velocities recorded at the same levels in the limbs of healthy subjects and in the clinically healthy limb of control patients. Algodystrophic patients actually had local circulatory abnormalities consisting of an increase in mean velocity with a diastolic component. A diastolic velocity superior to 3 cm/sec on the main arterial axis of the affected limb, or a difference of more than 5 cm/sec in mean velocity between the right and left sides provided an early diagnosis of algodystrophy with an 80 p. 100 sensitivity in this small series. Moreover, in 3 out of 10 cases Doppler velocimetry demonstrated abnormalities at varying levels of the contralateral limb.

[Radiological aspects of Mallory-Weiss syndrome (author's transl)]. / Aspect radiologique du syndrome de Mallory-Weiss.

A case of Mallory-Weiss syndrome was diagnosed by joint baryum study and endoscopy. A survey of publications (15 references) shows that this affection is frequent and could be responsable of 5 to 10% of upper digestive hemorrhage of which some are grave. But conventional radiology only exceptionnally reveals these superficial lesions. Without endoscopy and according the ulceration be deep, the radiologist should be able to reveal the lesion a sa niche.

[Urachal malformation. Clinical and radiological findings in one case (author's transl)]. / Malformations de l'ouraque Etude clinique et radiologique. a propos d'un cas.

An exceptional case of patient urachus, reported on a 54 year-old man, has led the authors to make an up-to-date survey on this malformative pathology. 4 types can be individualized, for which the roentgen diagnosis is quite simple (intravenous urography ultrasonography, fistulography). The risk of malignant degeneration obliges, after the search for other associated malformations, surgical cure and anatomo-pathologic verification.

[Primary mediastinal seminoma. Value of the assay of tumor markers before any surgery. Study of a case]. / Séminome médiastinal primitif. Intérêt du dosage des marqueurs tumoraux avant toute intervention chirurgicale. Etude d'un cas.

An excessive surgical excision of pulmonary parenchyme preceded the histological diagnosis of a mediastinal seminoma, concerning a 43 year-old man. Absence of all tumoral tracer during surgery did not permit to establish the difference between radiosensitive pure seminoma and impure seminoma of which repeated dosages should have improved medical strategy. In order to avoid, in the future, a similar error, in case of an anterior mediastinal tumor, the authors formally recommended, before all surgery, a dosage of HCG and AFP.

[Aorto-arteriography of the legs in the elderly. Tolerability and value. Report of 100 tests carried out consecutively in patients over 70 years of age]. / Aorto-artériographie des membres inférieurs chez le vieillard. Tolérance et intérêt. A propos de 100 examens réalisés consécutivement chez des patients de plus de 70 ans.

Over a period of 4 years, we have studied 100 consecutive cases of arteriographies, realized out of emergency, and concerning patients age 70 and above (average age 77). In 2/3 of cases, the arteriography was requested for a stage IV arteriopathy of the inferior limbs, the other 1/3 being equally distributed between stage II and III. On the technical plan, the femoral pathway with retrograde catheterization was mostly performed because femoral pulses were correct in most cases. Only one major complication occurred. The presurgery balance, patience and gentleness have permitted to reduce risks. We haven't observed any type of complications during the procedure in these elderly patients with polysystem disease (HT, diabetes, CVA, cardiopathology) latent renal insufficiency at this age did not create a problem because normal precautions were taken during procedure and new contrast products with low osmolarity used. The study of arteriographies by a personal scoring that we elaborated has clearly confirmed the distal and often bilateral nature of arterial lesions. The indications of this examination are of course already assessed by medico-surgical teams who select patients susceptible of enduring a by pass. The imagery obtained has allowed in almost 40% of cases either a revascularization act or a per cutaneous angioplasty, thus proving the advantages of this examination, finally little aggressive, in evaluation of these predominantly distal lesions in the elderly people.

TGIF Mutations in Human Holoprosencephaly: Correlation between Genotype and Phenotype.

Holoprosencephaly (HPE), which results from failed or incomplete midline forebrain division early in gestation, is the most common forebrain malformation. The etiology of HPE is complex and multifactorial. To date, at least 12 HPE-associated genes have been identified, including TGIF (transforming growth factor beta-induced factor), located on chromosome 18p11.3. TGIF encodes a transcriptional repressor of retinoid responses involved in TGF-ß signaling regulation, including Nodal signaling. TGIF mutations are reported in approximately 1-2% of patients with non-syndromic, non-chromosomal HPE. We combined data from our comprehensive studies of HPE with a literature search for all individuals with HPE and evidence of mutations affecting TGIF in order to establish the genotypic and phenotypic range. We describe 2 groups of patients: 34 with intragenic mutations and 21 with deletions of TGIF. These individuals, which were ascertained from our research group, in collaboration with other centers, and through a literature search, include 38 probands and 17 mutation-positive relatives. The majority of intragenic mutations occur in the TGIF homeodomain. Patients with mutations affecting TGIFrecapitulate the entire phenotypic spectrum observed in non-chromosomal, non-syndromic HPE. We identified a statistically significant difference between the 2 groups with respect to inheritance, as TGIF deletions were more likely to be de novo in comparison to TGIF mutations (χ(2) ((2)) = 6.97, p(permutated) = 0.0356). In addition, patients with TGIF deletions were also found to more commonly present with manifestations beyond the craniofacial and neuroanatomical features associated with HPE (p = 0.0030). These findings highlight differences in patients with intragenic mutations versus deletions affecting TGIF, and draw attention to the homeodomain region, which appears to be particularly relevant to HPE. These results may be useful for genetic counseling of affected patients.

[Camptomelic dysplasia. A case of survival for more than 4 years]. / La dysplasie campomélique. Un cas de survie au-delà de 4 ans.

The authors report a case of campomelic dwarfism concerning a girl presently 4 years old. The exceptionally long life span of this child has permitted a complete study of the clinical evolution and characteristic radiological features of this syndrome, probably transmitted as a genetic disease.