ABSTRACT
Nemaline myopathy is defined by the presence of nemaline bodies, or rods, on muscle biopsy. Facial and bulbar weakness in nemaline myopathy cause chewing and swallowing difficulties, recurrent aspiration, and poor control of oral secretions. This article discusses 5 patients (4 infants and 1 adolescent) with nemaline myopathy who received dietary supplementation with L-tyrosine (250 to 3000 mg/day). All 4 infants were reported to have an initial decrease in sialorrhoea and an increase in energy levels. The adolescent showed improved strength and exercise tolerance. No adverse effects of treatment were observed. Dietary tyrosine supplementation may improve bulbar function, activity levels, and exercise tolerance in nemaline myopathy.
Subject(s)
Dietary Supplements , Myopathies, Nemaline/drug therapy , Tyrosine/administration & dosage , Adolescent , Appetite/drug effects , Biopsy , Child, Preschool , Chromosomes, Human, Pair 1/genetics , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Microscopy, Electron , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Mutation, Missense , Myopathies, Nemaline/diagnosis , Myopathies, Nemaline/genetics , Myopathies, Nemaline/pathology , Phenotype , Sialorrhea/drug therapy , Sialorrhea/pathology , Treatment Outcome , Tropomyosin/genetics , Weight Gain/drug effectsABSTRACT
Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region at 9q21 (heterogeneity LOD score [HLOD]=6.6). In addition, meta-analyses with the addition of results from 186 more families (six populations; 1,033 genotyped individuals) showed genomewide significance for 10 more regions, including another novel region at 2q32-35 (P=.0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder.
Subject(s)
Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 9 , Cleft Lip/genetics , Cleft Palate/genetics , Genetic Linkage , Genetic Markers , Genetic Predisposition to Disease , Humans , Lod ScoreABSTRACT
A case-control survey of 48 children with nonsyndromic cleft lip or palate showed a significant increase in prevalence of maternal use of topical corticosteroid preparations in the first trimester of pregnancy, compared to 58 controls born in the same hospital; the odds ratio was 13.154, 95% confidence interval 1.67-586, P = 0.0049 on Fisher's exact two-tail test. The results were statistically significant although the wide confidence interval reflected the small sample size. Although older epidemiological studies have not detected any association between systemic corticosteroid treatment and the combined incidence of all congenital malformations, experimental studies over several decades have shown that maternal corticosteroid exposure in several species of animals is specifically associated with oral clefts. This association has been confirmed by more specific case-control surveys where the cases were children with cleft lip or palate and the exposure was maternal systemic corticosteroid treatment in the first trimester. Only one previous survey also analyzed topical corticosteroids, and it demonstrated an increased odds ratio for cleft lip or palate. A national survey of children with cleft palate will be necessary to evaluate the results of this pilot study.
