Blepharo-cheilo-dontic (BCD) syndrome.

Patients with the autosomal dominant ble-pharo-cheilo-dontic (BCD) syndrome have ectropion of lower eyelids, distichiasis of upper eyelids, euryblepharon, bilaterally cleft lip/palate, oligodontia, and conical crown form. Initially known under the eponym "Elschnig syndrome" (1912), BCD syndrome has been described in binary, ternary, and quaternary combination. There is overlap with the syndrome reported by Martínez et al. [1987], postaxial acrofacial dysostosis (Miller syndrome, Genée-Wiedemann syndrome), and a syndrome reported briefly by Warburg.

History of the cerebrohepatorenal syndrome of Zellweger and other peroxisomal disorders.

The history of the peroxisomal disorders (PDs), including the most frequent variant, the cerebrohepatorenal syndrome of Zellweger, can be divided into four phases. During the first phase, lasting from 1964 to 1972, the clinical and pathologic manifestations of Zellweger's syndrome (ZS) were explored and delineated. In 1973 it was found that ZS is due to the absence of peroxisomes in hepatocytes and renal tubular epithelial cells. With this discovery the second phase of ZS was initiated, which in subsequent years led to discovery of various defective peroxisomal functions. During the third phase, beginning in 1980, various other peroxisomal disorders were discovered, among them infantile Refsum's disease, hyperpipecolic acidemia, neonatal adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata. During 1986 the etiology of the various PDs was identified by complementation studies, marking the beginning of the fourth phase of the history of the peroxisomopathies. It was found that ZS, neonatal adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata represent different genetic entities, while Refsum's disease and hyperpipecolic acidemia are alleviated variants of ZS. Moreover, results of preliminary studies indicate that cells of one case of ZS may complement the cells of another ZS case, which could indicate genetic heterogeneity of ZS.

Familial Prader-Willi syndrome with apparently normal chromosomes.

We report on 4 sibs (2F, 2M) with Prader-Willi syndrome (PWS). Diagnosis was made clinically on the basis of history, behavior, and physical findings in 3 of the sibs. The other child had died at age 10 months with a history and clinical findings typical of first phase of PWS. Results of chromosome studies on the parents and surviving sibs were normal. The implications of this unusual familial occurrence for our understanding of PWS are discussed.

Frequency of cerebral infarction in patients with inherited neuromuscular diseases.

We evaluated the frequency of cerebral infarction in 131 patients with Duchenne's muscular dystrophy, myotonic dystrophy, Becker's muscular dystrophy, or Friedreich's ataxia. Electrocardiographic abnormalities were found in 83% of patients with Duchenne's muscular dystrophy, 56% with myotonic dystrophy, 50% with Becker's muscular dystrophy, and 25% with Friedreich's ataxia. Atrial flutter occurred in 2.3% of the patients, and atrial fibrillation in only 0.9%. Evidence of cerebral infarction was found in only 2 patients (1.5%). Both patients had cardiomyopathy and either atrial fibrillation or flutter. Despite frequent cardiac involvement, cerebral infarction is an uncommon occurrence in patients with inherited neuromuscular diseases.

Magnetic resonance imaging of children with Duchenne muscular dystrophy.

Eight children representing a spectrum of clinical states of biopsy-proven Duchenne muscular dystrophy (DMD) underwent magnetic resonance (MR) scans to assess the degree of muscular involvement and disease progression. Five muscle groups (neck, shoulder girdle, pelvic girdle, thigh and calf) were evaluated. In each case, involved muscles were clearly demarcated. Image estimates of disease severity by degree of muscle involvement correlated well with clinical staging. In our experience MR is useful for assessment of disease stage, selection of appropriate muscles for biopsy and planning for courses of physical and rehabilitation therapy.

Myopathy in Marinesco-Sjogren syndrome.

Progressive muscular weakness, hypotonia and atrophy are among the cardinal signs of the Marinesco-Sjogren syndrome but have not been extensively investigated. Our study focused on 6 related patients who are members of an inbred population. Muscle biopsies revealed myopathic alterations with variation of fiber size, rounding, degeneration and regeneration of fibers, internalization of nuclei and endomysial fat and fibrosis. Most patients had elevated serum creatine kinase levels. One patient revealed endstage neuromuscular disease and had normal serum creatine kinase levels. Of particular interest was the finding of conspicuous myopathy in 2 young children. Thus far, it has not been appreciated that myopathy represents an early sign of the Marinesco-Sjogren syndrome.

Börjeson-Forssman-Lehmann syndrome: further delineation in five cases.

We have studied five males with Börjeson-Forssman-Lehmann syndrome (BFLS) from two unrelated families. They had a characteristic facial appearance with prominent supraorbital ridges, deep-set eyes, ptosis, and large ears, as well as obesity, severe mental retardation, hypotonia, and hypogonadism. Ophthalmologic, EEG, and skeletal abnormalities were also present. The findings in several presumed or possible heterozygous women were evaluated and suggested a wide range of phenotypic effects varying between apparent normality to mild or moderately evident BFLS manifestations. The observed pattern of occurrence of the BFLS in our two families provides strong support for X-linked inheritance. In clinically normal female relatives at risk for being carriers of BFLS, we have been unsuccessful in identifying a reliable screening test. The condition in our and previously reported patients was contrasted with other malformation syndromes and our findings support the conclusion that BFLS is a distinct and clinically identifiable disorder.

[Duchenne's muscular dystrophy: also in girls?]. / Duchennesche Muskeldystrophie: Auch bei Mädchen?

Duchenne's muscular dystrophy is inherited as a recessive X-linked trait: Even-though it rarely appears in females it can be seen. We have examined 5 children of one family. Two boys and one girl showed typical symptoms and clinical as well as light- and electronmicroscopical findings of this disease. In order to understand the mode of the genetic pattern, we have analysed the chromosomes, proved the fatherhood and assured the increased Ca-pooling in non-necrotic muscle fibers; in vitro-examinations of the amino-acid-incorporation in ribosomes and of the synthesis of collagen in muscular cells were done as well. Evaluating all of the results, the inheritance must be X-linked recessive and the girl, with high incidence, is a so called "manifesting carrier". The explanation offers Lyons hypothesis, which suggests that in most of the girl's muscle cells the X-Chromosomes, inherited from the mother, are active and lead to the manifestation of the illness. Consequences in advising the family genetically must be taken.

The floppy infant: a practical approach.

Cerebral, non paralytic and peripheral paralytic hypotonia are briefly discussed. Criteria which help in the differential diagnosis are emphasized. In the usual cerebral hypotonia, muscle strength is preserved but muscle tone is decreased. However, there are a few conditions in which cerebral hypotonia is severe enough to resemble paralytic hypotonia. These conditions include the Prader-Willi syndrome (first phase), the Zellweger syndrome and some cases of congenital myotonic dystrophy. In peripheral or paralytic hypotonia muscle weakness and hypotonia go hand-in-hand. A few practical diagnostic criteria are given which allow the differentiation between anterior horn cell disease, polyneuropathy, neonatal myasthenia and myopathy. Finally, essential or benign hypotonia is briefly alluded to.