The gynecological and reproductive histories of 193 women from fragile X families were surveyed. Among the 101 carriers of the premutation, 14 experienced premature menopause, contrarily to their 37 fully mutated and 55 noncarrier female relatives. Although premature menopause showed a tendency to cluster in certain fragile X families, as a group, the premutated women experienced menopause earlier than noncarriers. This suggests that premature menopause may be the extreme effect of a spectrum of ovarian anomalies associated with the fragile X premutation.

In Duchenne muscular dystrophy, the progression of the disease is always severe and predictable, while in Becker dystrophy there is a wide variability (intra and inter familial) in the severity of the phenotype. We report here a family in which the proband, who is currently 15 years old, is showing a severe DMD progression, while his affected maternal uncle, aged 29, has a more benign course, compatible with BMD. No DNA deletion was detected in both patients. Dystrophin analysis through immunofluorescence and western blotting showed a negative pattern in the youngest patient and a positive one in the oldest. Apparently, this is the first report on intrafamilial variability in dystrophin abundance correlated with a difference in the severity of the phenotype.

The differential clinical diagnosis between the X-linked muscular dystrophies (DMD and BMD) and autosomal recessive limb-girdle muscular dystrophy (LGMD), which is extremely important for genetic counseling, may be very difficult. The aim of the present report is to describe clinical and laboratory findings in patients from large families, with AR inheritance, in an attempt to characterize better cases which have been diagnosed as LGMD compared with the X-linked forms. The main features analysed are: age of onset and of confinement to a wheelchair, reproductive performance, serum enzymes (CK and PK) and dystrophin assessment (through immunohistochemistry and Western blot). Twenty-two families, with 62 affected patients diagnosed as limb-girdle muscular dystrophy, were included in this report. In 19 families, the patients had a milder clinical course, while in the remaining 3, the progression of the disease was continuous and clinically similar to X-linked DMD ("DMD-like"). A high consanguinity rate was observed among the parents of the affected patients (77%). No major clinical difference was observed between the X-linked and the AR forms. However, muscle dystrophin was found qualitatively and quantitatively normal in the autosomal forms but absent or abnormal in the X-linked ones. The reproductive performance was significantly higher for male than female patients. In addition, a surprising finding was the significantly greater fitness estimated for male LGMD cases as compared with Becker patients of comparable age studied in our center. The implications of such findings are discussed.

Serum creatine-kinase (CK) activities were determined in 536 patients affected with X-linked muscular dystrophy (456 with Duchenne or DMD and 80 with Becker or BMD) and serum pyruvate-kinase (PK) in 360 among them (309 DMD and 51 BMD). The aim of this investigation was to assess the variability and rate of decrease in serum activity in DMD as compared with BMD as a function of age and in DMD as a function of Vignos scale as well. In DMD, maximum CK and PK activities were found around 1–6 years old and the average rate of decline according to age was estimated as 0.18 per year and 0.27–0.29 for both enzymes as a function of Vignos scale (assessed in 291 cases). For BMD, maximum serum enzyme levels were found around 10–15 years old and the rate of decline of serum activity per year was 0.06 for CK and 0.07 for PK. If maximum levels of serum enzyme reflect active muscle degeneration and the rate of decline per year to progressive loss of muscle mass (responsible for the release of muscle enzymes to the blood stream) our observations suggest: (a) active muscle degeneration occurs, on average, 5 years later in the group of outliers and 10 years later in BMD as compared with severe DMD; (b) the rate in which muscle mass is lost is significantly greater in DMD than in BMD and therefore serum enzyme determinations may represent an important test for evaluation of therapeutic trials; (c) serum enzymes determination may represent an important preliminary test to discriminate in a proportion of young patients if they will develop a severe or milder phenotype.

Seventy-five male and 50 female students from 2 special schools for mildly, moderately retarded, or borderline individuals were screened clinically and cytogenetically in order to estimate the contribution of fragile X [fra(X)] syndrome to the cause of mental retardation in Brazil. We found 6 males (8%) from 4 families and 2 unrelated females (4%) with fra(X) chromosomes. One male and one female were isolated cases. The estimated frequency of Martin-Bell [fra(X)] syndrome among mentally impaired individuals in Brazil was similar to that previously reported in other countries.

We have evaluated the relation between height and rate of clinical progression in boys with Duchenne muscular dystrophy (DMD). In all, 111 DMD patients with age ranging from 2 to 23 years (mean 8.2 +/- 3.4 years) were assessed; of these patients, 92 had their height measured. Clinical course was determined through Vignos scale of functional disability, motor ability, and timed functional tests. All patients had grossly elevated serum creatine-kinase (CK) and pyruvate-kinase (PK) levels. When height was adjusted for patients' age, a statistically significant correlation was found between height and clinical course (positive with Vignos scale and negative with motor ability), suggesting that smaller boys have a better clinical course than taller patients of comparable age. These results support our previous hypothesis and suggest that growth inhibition seems to be effective in diminishing the progression of DMD.

American Journal of Medical GeneticsVolume 27, Issue 4 p. 993-995 Letter to the Editor Mazindol and growth hormone inhibition in Duchenne muscular dystrophy Mayana Zatz, Mayana Zatz Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorMariz Vainzof, Mariz Vainzof Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorDebora Rapaport, Debora Rapaport Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorJane Maria Leite Da Rocha, Jane Maria Leite Da Rocha Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorRita de Cássia M. Pavanello, Rita de Cássia M. Pavanello Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorRoberto T. B. Betti, Roberto T. B. Betti Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorJohn M. Opitz, John M. Opitz EditorSearch for more papers by this authorJames F. Reynolds, James F. Reynolds EditorSearch for more papers by this author Mayana Zatz, Mayana Zatz Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorMariz Vainzof, Mariz Vainzof Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorDebora Rapaport, Debora Rapaport Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorJane Maria Leite Da Rocha, Jane Maria Leite Da Rocha Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorRita de Cássia M. Pavanello, Rita de Cássia M. Pavanello Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorRoberto T. B. Betti, Roberto T. B. Betti Departamento de Biologia Universidade de São Paulo São Paulo BrasilSearch for more papers by this authorJohn M. Opitz, John M. Opitz EditorSearch for more papers by this authorJames F. Reynolds, James F. Reynolds EditorSearch for more papers by this author First published: August 1987 https://doi.org/10.1002/ajmg.1320270433Citations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume27, Issue4August 1987Pages 993-995 RelatedInformation