RESUMO
OBJECTIVE: In our general experience, about 2% of samples referred for fragile X testing showed positive results on Southern blot analysis. The aim of this project was to determine whether screening criteria could be developed to increase the proportion of positive test results without sacrificing sensitivity. STUDY DESIGN: We retrospectively analyzed nine clinical characteristics from patient records of 273 male and 62 female pediatric probands (average age, 5.7 years) referred for fragile X testing. The characteristics included mental retardation, family history of mental retardation, large or prominent ears, elongated face, attention deficit hyperactivity disorder, autistic-like behavior, simian crease, macroorchidism, and hyperextensible joints. These were scored as 2 if present, 1 If borderline present, and 0 if absent. RESULTS: Analysis of the nine characteristics identified three (simian crease, macroorchidism, and hyperextensible joints) with low frequency and statistical insignificance, which were therefore eliminated. With the use of the remaining six characteristics, If a score of 5 or more was used as the criterion for requesting fragle X testing, then close to 60% of those tests from our patient population could have been eliminated without missing any positive cases. The validity of our threshold score of 5 was subsequently confirmed among an additional six cases of fragile X syndrome. CONCLUSION: With our simplified six-item clinical checklist, 60% of testing could have been eliminated, thereby improving the cost-effectiveness of fragile X testing and increasing the proportion of cases with positive results by threefold.
Assuntos
Síndrome do Cromossomo X Frágil/diagnóstico , Programas de Rastreamento/métodos , Análise Custo-Benefício , Feminino , Humanos , Masculino , Programas de Rastreamento/economia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
The authors report a case of Möbius syndrome with Poland syndrome, cleft palate, dextrocardia, mandibular hypoplasia, and multiple areas of diffuse brain volume loss. Karyotype demonstrated a t(1;11)(p22;p13) translocation in the patient and his phenotypically normal father and brother. This case extends the spectrum of congenital disorders that are associated with Möbius syndrome and raises the possibility of genetic heterogeneity for the Möbius disorder.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 1 , Paralisia Facial/genética , Oftalmoplegia/genética , Translocação Genética , Mapeamento Cromossômico , Humanos , Recém-Nascido , Cariotipagem , MasculinoRESUMO
A child with manifestations of acrogeria and metageria, two "premature aging" syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers-Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson-Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging.
Assuntos
Progéria/classificação , Células Cultivadas , Senescência Celular/fisiologia , DNA/efeitos dos fármacos , DNA/efeitos da radiação , Dano ao DNA , Humanos , Lactente , Masculino , Progéria/diagnóstico , Progéria/genética , Troca de Cromátide Irmã , Raios UltravioletaRESUMO
Familial expression of inadequate virilization of 46XY siblings is often reported as an isolated anomaly. We recently evaluated two families with 2 siblings who had a 46XY karyotype, ambiguous genitalia or micropenis, facial anomalies and mental retardation. There is no evidence of gonadotropin deficiency, defects of steroidogenesis, or androgen insensitivity. While there was a testosterone response to human chorionic gonadotropin stimulation in all 3 tested, gonadotropin levels were elevated in 2 of the infants suggestive of faulty seminiferous tubules, 1 of whom later had elevated luteinizing hormone levels. These kindreds may represent a new syndrome with either an X-linked recessive or sex-limited autosomal dominant form of inheritance, with partial testicular failure, multiple congenital anomalies, and mental retardation.
Assuntos
Sistema Nervoso Central/anormalidades , Genitália Masculina/anormalidades , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal/genética , Células Cultivadas , Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/fisiopatologia , Feminino , Disgenesia Gonadal 46 XY/fisiopatologia , Humanos , Recém-Nascido , Cariotipagem , Masculino , Linhagem , Receptores Androgênicos/metabolismo , Pele/metabolismoRESUMO
Fifty-nine patients with Prader-Willi syndrome (PWS) (including three blacks) were enrolled in a behavior modification program including dietary restriction, nutritional education for self-management of food intake, and exercise. Caloric intake for most patients was 700-800 calories per day. The average stay per patient was 5 weeks with a mean weight loss of 6.6 kg. Thirty-one patients (53%) had apparently normal chromosomes compared to 25 patients (42%) with apparent 15(q12) deletion. Three patients had other chromosome abnormalities including two with mosaicism for idic(15)(q11) and one with a de novo apparently balanced translocation t(8q;18q). There were no differences in manifestations or the effects of the behavior modification program between chromosomally normal and abnormal patients. However, the mean weight loss in the 59 PWS patients was less than would have been expected based on their calculated daily caloric requirements suggesting that PWS patients have reduced caloric needs per unit of body weight compared to normal individuals. Supporting this also was that weight maintenance could be accomplished with only 1000 calories per day on the average. In general, behavioral response to the modification program was successful in that tantrum responses, while not eliminated, were reduced in frequency and severity.