iences 263 (2007) 49–53www.elsevier.com/locate/jns

Journal of the Neurological Sc

Sleep quality in Facioscapulohumeral muscular dystrophy

Giacomo Della Marca a,⁎, Roberto Frusciante a, Catello Vollono a,b, Serena Dittoni a,Giuliana Galluzzi c, Cristina Buccarella a, Anna Modoni a, Salvatore Mazza a,

Pietro Attilio Tonali a,b, Enzo Ricci a

a Department of Neurosciences, Catholic University, Rome, Italyb Fondazione Pro Juventute Don C. Gnocchi, Rome, Italy

c Centre for Neuromuscular Diseases, UILDM-Rome Section, Rome, Italy

Received 29 March 2007; received in revised form 19 May 2007; accepted 23 May 2007Available online 26 June 2007

Abstract

Objective: To evaluate the subjective sleep quality, the prevalence of daytime sleepiness and the risk of sleep-related upper airwaysobstruction in patients with genetically proven Facioscapulohumeral muscular dystrophy (FSHD). FSHD is an autosomal dominantmyopathy, characterized by an early involvement of facial and scapular muscles with eventual spreading to pelvic and lower limb muscles.Patients and methods: Forty-six patients were enrolled, 27 women and 19 men, mean age 43.6±14.1 years. Study protocol included: aClinical Severity Scale (CSS) for FSHD, Pittsburgh Sleep Quality Index (PSQI), Italian version of the Epworth Sleepiness Scale (ESS) andthe search for clinical predictors of sleep-related airways obstruction.Results: Twenty-seven patients presented snoring, 12 reported respiratory pauses during sleep. One half (23/46) had PSQI scores above thenormal threshold (=5). Correlations were found between the CSS and: the total PSQI score, the components C1 sleep quality, C5 sleepdisturbances, C7 daytime dysfunction.Conclusion: Our data support the hypothesis that patients with FSHD have an impaired sleep quality, and that this impairment is directlyrelated to the severity of the disease. A systematic polysomnographic evaluation of these patients will be necessary to confirm the presence ofsleep disruption and to clarify its pathogenesis.© 2007 Elsevier B.V. All rights reserved.

Keywords: Sleep; Facioscapulohumeral muscular dystrophy; Sleepiness; Sleep quality; OSAS; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale

1. Introduction

Facioscapulohumeral muscular dystrophy (FSHD) is anautosomal dominant disease with an estimated prevalence of1:20,000, corresponding to the third most frequent form ofMuscular Dystrophy, after Duchenne Dystrophy and Myo-tonic Dystrophy. The gene for the disease has been mappedto the long arm of chromosome 4 (region 4q35) [1,2]. In this

⁎ Corresponding author. Unit of Sleep Medicine, Department ofNeurosciences, Catholic University, Policlinico Universitario “A. Gemelli”,L.go A. Gemelli, 8 - 00168 Rome Italy. Tel.: +39 06 30154276; fax: +39 0635501909.

E-mail address: dellamarca@rm.unicatt.it (G. Della Marca).

0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved.doi:10.1016/j.jns.2007.05.028

region, which carries a long stretch of 3.3 kb KpnI repeatunits called D4Z4, the 4q35 telomeric probe p13E-11 hasbeen shown to detect EcoRI polymorphic fragments largerthan 40 kb in healthy individuals and smaller fragments (10to 40 kb in size) in both sporadic and familial cases of FSHD.The size variation of the 4q35 fragments in affectedindividuals is due to a deletion which involves the D4Z4locus, and the clinical features of FSHD develop when thenumber of the KpnI repeat units falls below a criticalthreshold [3]. No transcripts unambiguously derived fromthis locus have been identified in vivo, either in muscle or inother tissues [4], and an increasing number of observationssuggest that epigenetic mechanisms are involved in thepathogenesis of the disease [5]. However, studies on

50 G. Della Marca et al. / Journal of the Neurological Sciences 263 (2007) 49–53

genotype–phenotype correlation unequivocally showed thatthe number of KpnI repeats left on the shortened chromo-some 4 inversely correlates with the severity of the disease[6–8].

The phenotypic spectrum is wide and heterogeneous. Themost typical clinical presentation is characterized by an earlyinvolvement of facial and scapular muscles with eventualspreading to pelvic and lower limb muscles; foot extensorsare often affected earlier and more severely than pelvicmuscles. The age of onset, the clinical severity and thepattern of muscular involvement show a high degree ofvariability both between and within families. Diseaseseverity ranges from very mild forms, in which the patientcan be unaware of the disease, to severe muscularimpairment in wheelchair-bound patients [9]. Extramuscularinvolvement includes neurosensorial hearing loss and retinalvasculopathy [10], which rarely reach clinical relevance.Mental impairment is rare too, occurring in the most severeform of the disease, with infantile onset. The involvement ofrespiratory muscles is uncommon. In a large Dutch series[11], only 10 patients (approximately 1%) suffered fromrespiratory insufficiency which required nocturnal ventila-tory support.

Sleep abnormalities, i.e. subjectively impaired sleepquality and excessive daytime sleepiness, are common inmuscular dystrophies [12–14]. Sleep quality impairment anddaytime somnolence in these diseases are often secondary toSDB. In particular, SDB has been described in Duchennemuscular dystrophy [15], in Myotonic dystrophy [16] and inlimb girdle muscular dystrophy [17]. Breathing abnormal-ities in these diseases may consist either in alveolarhypoventilation of central origin, due to impaired ventilatorycontrol [16–18], or in upper airways obstruction, due topharyngeal muscles weakness and collapse [15,19]. A searchof the PubMed Medline, using ‘Facioscapulohumeral’ and‘sleep’ as key words, did not reveal any paper systematicallyaddressing the issue of sleep disturbances in FSHD. In areport by Bushby et al. [20], concerning 4 patients withFSHD and chronic muscular pain, it is stated that all patientscomplained of disturbed sleep.

The aim of the present study was to evaluate thesubjective sleep quality, the prevalence of excessive daytimesleepiness (EDS) and the risk of sleep-related upper airwaysobstruction in a large sample of patients affected bygenetically proven FSHD.

2. Methods

2.1. Patients

Forty-eight consecutive patients affected by FSHD,followed at the Institute of Neurology of the CatholicUniversity in Rome, were enrolled. Diagnosis was made on aclinical basis [21], and confirmed by means of genetic tests.In particular, restriction of genomic DNA, 32P-labeling, andhybridization with L1LA5 (D4S163), pH30 (D4S139), and

p13E-11 (D4F104S1) were performed as described [22,23].Pulsed field gel electrophoresis (PFGE) analysis of p13E-11alleles was performed as described [23]. One patient wasexcluded because the dimension of the mutated fragmentwas longer than 50 Kb; another patient was excludedbecause of genetic mosaicism. Therefore, 46 patients werefinally enrolled, 27 women and 19 men, with an average ageof 43.6±14.1 years. The study design was approved by thelocal Ethical committee, and all the patients were fullyinformed and gave their written consent. All patientsunderwent a full medical and neurological evaluation. Inorder to measure the clinical severity of the disease, aClinical Severity Scale (CSS) was applied, with scoresranging from 0.5 (mild) to 5 (severe). Muscle strength wasevaluated by using the Manual Muscle Testing. For adetailed description of the scale, see Ricci et al. [8].

2.2. Sleep quality evaluation

Subjective evaluation of sleep quality was performed bythe Pittsburgh Sleep Quality Index (PSQI) [24]. The Italianversion has been translated from English into Italian and thenretranslated for comparison with the original version. Aglobal score N5 was considered as an indicator of relevantsleep disturbances [24,25]. For the evaluation of EDS, thevalidated Italian version of the Epworth Sleepiness Scale(ESS) [26] was applied. Moreover, in all subjects anevaluation of the symptoms and clinical signs predictors ofOSAS were performed, including neck circumference, BodyMass Index (BMI), presence of habitual snoring, nocturia,morning headache, arterial hypertension, and apneasreported by the bed-partner.

2.3. Statistical analysis

The correlation between sleep parameters (PSQI, includ-ing single sections and total score, and ESS score) andclinical measures (BMI, neck circumference, CSS andfragment size) were evaluated by means of the Pearsoncorrelation index. Due to multiple comparisons, the criticalvalue of the Pearson product–moment correlation coefficientwas set to r(44)=0.34, corresponding to a significance levelpb0.02.

3. Results

The average size of the p13E-11 EcoRI fragment was 21.6±6.2 kb. Pathological cut-off was considered for size ≤40 kb.The mean Clinical Severity score was 2.8±1.5. As concerns thePSQI, the average score in the sample, was 5.9±3.8; since aPSQIN5 is considered abnormal [24], 23 patients (50%)showed pathological levels. The ESS average score was 4.4±3.3, only two patients presented a ESS scoreN10. Average BMIwas 24.9±4.6 Kg/m2; average neck circumference was 37.2±4.3 cm. Two patients (#32 and #39) presented both BMI andneck circumference above the levels considered at risk for sleep

Table 1Demographic, genetic and clinical data, PSQI and ESS scores in the 46 FSHD patients

Pittsburgh Sleep Quality Index (PSQI)

No. Age Sex BMI Neck 4q35 CSS ESS C1 C2 C3 C4 C5 C6 C7 Total

1 64 F 20.6 33 21 3 4 1 1 0 0 1 2 1 62 44 M 24.3 38 22 1.5 0 1 0 1 0 0 2 1 53 54 F 20.0 32 21 3.5 4 1 1 0 0 1 0 0 34 42 F 29.3 40 15 4 8 2 3 3 3 3 0 2 165 57 M 23.8 42 24 3.5 10 1 0 1 1 2 0 1 66 35 F 21.4 34 17 3 4 2 2 2 1 2 0 0 97 42 M 26.3 42 26 3 4 1 1 0 0 1 0 2 58 27 F 21.3 32 21 1 5 0 0 1 0 1 0 0 29 54 M 23.7 40 21 4 3 1 1 0 0 2 0 0 410 30 F 21.3 31 21 0 5 0 0 1 0 1 0 0 211 48 M 25.8 41 22 1 1 1 1 1 1 1 0 0 512 59 F 29.0 37 28 3.5 7 2 1 1 3 3 3 2 1513 52 F 37.3 39 15 4.5 6 2 0 2 1 2 3 1 1114 29 F 20.0 31 15 4.5 1 1 2 0 0 1 0 1 515 26 M 21.9 37 15 4.5 3 1 0 1 0 1 0 1 416 45 M 26.9 42 23 3 1 1 1 1 0 3 0 1 717 61 M 27.1 39 16 4.5 3 1 0 1 0 3 0 2 718 36 F 18.8 32 17 4 5 1 1 1 1 2 0 1 719 35 F 22.0 33 19 4 1 0 1 0 0 1 0 1 320 31 M 27.5 41 35 1 3 1 0 1 1 1 0 0 421 26 F 18.6 30 16 1 9 0 0 0 0 1 0 1 222 60 F 19.1 32 19 3.5 3 2 1 2 3 2 3 2 1523 40 F 23.4 34 20 3.5 16 1 1 1 0 1 0 1 524 27 M 19.6 39 20 4 5 1 1 0 0 1 0 1 425 26 F 18.8 31 18 1.5 5 1 2 1 1 1 0 0 626 33 F 21.2 31 19 1 3 1 1 1 0 2 0 1 627 18 M 23.9 36 15 2.5 0 0 0 0 0 1 0 0 128 26 F 26.2 34 15 1 5 0 0 0 0 1 0 0 129 68 M 21.8 39 33 3.5 4 0 0 0 0 1 0 0 130 48 F 33.2 41 16 4 9 1 1 2 0 2 0 1 731 44 M 27.8 44 22 3.5 1 0 0 0 0 1 0 0 132 50 F 29.4 42 36 4 3 1 2 1 3 2 3 1 1333 71 F 21.5 35 27 3.5 1 1 2 0 3 1 0 0 734 36 M 25.7 46 19 2.5 5 0 0 1 0 1 0 0 235 38 F 21.7 32 23 3 4 1 1 1 0 1 0 2 636 64 M 24.2 40 18 3 2 1 0 1 0 2 0 0 437 57 M 28.0 42 21 2.5 5 1 2 2 0 2 0 1 838 26 M 26.2 41 27 1 0 1 1 1 0 1 0 0 439 26 M 35.7 45 26 1.5 1 0 1 0 0 1 0 0 240 60 F 21.3 33 17 4 6 1 1 2 3 2 0 1 1041 45 F 33.4 37 35 3 13 2 0 2 0 2 0 1 742 54 F 33.3 38 29 0.5 10 1 0 2 0 2 0 1 643 36 F 25.4 39 10 4 3 1 0 0 1 1 0 0 344 64 F 29.6 40 17 3.5 5 1 1 1 1 2 0 0 645 59 M 26.2 40 32 4 2 1 2 2 3 2 0 1 1146 36 F 24.6 35 32 4 5 2 1 1 2 2 0 1 9Mean 43.67 24.96 37.22 21.65 3.04 4.41 0.93 0.80 0.91 0.70 1.52 0.35 0.72 5.93SD 14.07 4.64 4.35 6.24 1.25 3.36 0.61 0.78 0.78 1.09 0.69 0.92 0.69 3.77

BMI = Body Mass Index (Kg/m2); Neck = neck circumference (cm); 4q35 = size of the 4q35 deleted fragment (Kb, Kilobases); CSS = Clinical Severity Scale;ESS = Epworth Sleepiness Scale; C1–C7: subcomponents of the PSQI; Total = global PSQI score; SD = standard deviation.

51G. Della Marca et al. / Journal of the Neurological Sciences 263 (2007) 49–53

disordered breathing (BMI N29 kg/m2; neck circumferenceN41 cm for women, N43 cm for men). Twenty-seven patientspresented snoring (occasional or frequent, referred by the bed-partner), and 12 presented respiratory pauses during sleep(occasional or frequent, referred by the bed-partner). High bloodpressure was present in 17 patients, nocturia in 14, morningheadache in 9.

Significant correlations were found between the age andthe CSS (r(44)=0.35; pb0.02), and between the CSS andthe components of the PSQI: total PSQI score (r(44)=0.36;pb0.02), components C1 sleep quality (r(44) =0.45;pb0.02), C5 sleep disturbances, (r(44)=0.36; pb0.02),and C7 daytime dysfunction (r(44)=0.36). No correlationwas found between the CSS and the components C2 sleep

52 G. Della Marca et al. / Journal of the Neurological Sciences 263 (2007) 49–53

onset latency (r(44)=0.18), C3 sleep duration (r(44)=0.09),C4 sleep efficiency (r(44)=0.30) and C6 use of sleepmedications (r(44)=0.37).

No significant correlations were found between the EcoRIfragment size and the subjective sleep parameters evaluated,nor between the ESS scores and other clinical data.

Demographic and clinical details and the scale scores inall FSHD patients are listed in Table 1.

4. Discussion

Our observation concerns the subjective evaluation ofsleep quality and daytime sleepiness in a population ofgenetically proven FSHD.

The main finding of the study is the reduced sleep qualityin FSHD patients. One half of the patients (23/46) showedvalues N5 (which is considered the cut-off for normality),and the average PSQI value in the group was 5.9±3.8.Moreover, the analysis of the correlation between the CSS,which is a validated index of severity of the disease [8],and the PSQI components showed an inverse correlationbetween subjective sleep quality and the clinical severity ofFSHD. In particular, the analysis of the components of thePSQI (Table 1) revealed that the principal determinants ofpoor sleep quality, and those which were significantly relatedto severity of clinical involvement, were sleep quality (C1),sleep disturbances (C5) and daytime dysfunction (C7). Noabnormal levels of daytime sleepiness were measured by theESS (only 2 patients showed scores ≥n13).

The possible causes for sleep disruption and poor sleepquality in FSHD are numerous, and our study design onlyallows speculations. One possible cause could be sleepdisordered breathing (SDB). Obesity is a risk factor forObstructive Sleep Apnea Syndrome (OSAS), and our resultsreveal that 4 out of 5 obese patients (BMIN30) had PSQIscores over 5; while for the remaining non-obese subjects,only 19 out of 41 (46%) had PSQI scores over 5. SDB and inparticular OSAS have been described in several forms ofmuscular dystrophy, including Duchenne muscular dystro-phy [15], Myotonic dystrophy [16] and Limb Girdlemuscular dystrophy [17]. With regard to the risk of OSAS,the clinical observation in our sample showed controversialfindings: even though the anthropometric measures (BMIand neck circumference) revealed a risk of SDB in only 2patients, snoring (occasional or habitual) and sleep-relatedrespiratory pauses were reported in many cases (27 and 12respectively). This is in agreement with the observation thatpatients with neuromuscular impairment could present SDBeven in the absence of obesity or other morphologicalabnormalities of the upper airways, as revealed by the BMIand neck circumference [27]; in these patients history andphysical examination must be considered poor predictors ofSDB, since they have high specificity but low sensitivity[28]. SDB is strictly associated with impaired daytimefunction and increased diurnal sleepiness. In this respect, ourdata seem discordant, since the items of PSQI related with

diurnal dysfunction showed relatively high scores in ourpopulation (mean=0.72±0.69) with strong direct relation withthe clinical severity index, whereas the Epworth scores werenormal inmost subjects. This discrepancy probably depends onthe differences between the two scales, since the ESS is a ‘pure’sleepiness scale, whereas the PSQI, in the item #7, includes 2questions concerning ‘sleepiness’ and ‘enthusiasm’.

Another possible cause of sleep disruption in dystrophicpatients is nocturnal pain [5,29]. Nocturnal pain, localized inneck, shoulders and low back, has been observed in morethan a half of FSHD patients [5,20].

Also reduced spontaneous motility during sleep can behypothesized as a mechanism of sleep disruption in FSHD.Body movements during sleep are periodically necessary toallow changes of body position and to avoid peripheral nervescompressions, resulting in paresthesias and pain. Reducedmotility during sleep is reported by FSHD patients, but hasnever been addressed by systematic video–polygraphicrecordings during sleep. The hypothesis that poor sleepquality is provoked by reduced spontaneous motility duringsleep is in agreement with the finding that sleep disruption isclosely, directly related to the CSS (which measures,essentially, motility and muscle strength [8].

Finally, a functional involvement of central nervoussystem in FSHD could be hypothesized. In fact, although aclinically relevant central dysfunction, with mental retarda-tion and epilepsy, has been observed only in extremelysevere forms of FSHD [30], demonstrated changes in motorcortex excitability also in subject with relatively mild FSHD.

In conclusion, our data support the hypothesis thatpatients with FSHD have an impaired sleep quality, andthat this impairment is directly related to the severity of thedisease. Some clinical observation suggests the possibility ofSDB, though the normal levels of daytime sleepiness do notsupport this hypothesis. Other possible causes of sleepdisruption which can be simply hypothesized, are nocturnalpain or reduced spontaneous motility in sleep. Though thePSQI [24] and the ESS [26] are widely employed, validatedinstruments for the subjective measurement of sleep qualityand daytime sleepiness, especially in large and homogeneouspopulations, a more extensive and systematic video–polysomnographic evaluation of these patients is essentialto confirm the presence of sleep disruption, to assess or ruleout SDB, and to clarify the pathogenesis of sleep disorders.

References

[1] Sarfarazi M, Wijmenga C, Upadhyaya M, et al. Regional mappingof facioscapulohumeral muscular dystrophy gene on 4q35: combinedanalysis of an international consortium. Am J Hum Genet1992;51:396–403.

[2] Wijmenga C, Hewitt JE, Sandkuijl LA, et al. Chromosome 4q DNArearrangements associated with facioscapulohumeral muscular dystro-phy. Nat Genet 1992;2:26–30.

[3] Van Deutekom JC, Wijmenga C, van Tienhoven EA, et al. FSHDassociated DNA rearrangements are due to deletions of integral copiesof a 3.2 kb tandemly repeated unit. Hum Mol Genet 1993;2:2037–42.

53G. Della Marca et al. / Journal of the Neurological Sciences 263 (2007) 49–53

[4] Hewitt JE, Lyle R, Clark LN, et al. Analysis of the tandem repeat locusD4Z4 associated with facioscapulohumeral muscular dystrophy. HumMol Genet 1994;3:1287–95.

[5] Tawil R, Van Der Maarel SM. Facioscapulohumeral musculardystrophy. Muscle Nerve 2006;34:1–15.

[6] Lunt PW, Jardine PE, Koch MC, et al. Correlation between fragmentsize at D4F104S1 and age at onset or at wheelchair use, with a possiblegenerational effect, accounts for much phenotypic variation in 4q35-facioscapulohumeral muscular dystrophy (FSHD). Hum Mol Genet1995;4:951–8.

[7] Tawil R, Forrester J, Griggs RC, et al. Evidence for anticipation andassociation of deletion size with severity in facioscapulohumeralmuscular dystrophy. The FSH-DYGroup. Ann Neurol 1996;39:744–8.

[8] Ricci E, Galluzzi G, Deidda G, et al. Progress in the moleculardiagnosis of facioscapulohumeral muscular dystrophy and correlationbetween the number of KpnI repeats at the 4q35 locus and clinicalphenotype. Ann Neurol 1999;45:751–7.

[9] Padberg, G.W. Facioscapulohumeral disease. Thesis. Leiden Univer-sity, Leiden, The Netherlands, 1982.

[10] Padberg GW, Brouwer OF, de Keizer RJW, et al. On the significance ofretinal vascular disease and hearing loss in facioscapulohumeralmuscular dystrophy. Muscle Nerve 1995;2(Suppl 2):S73–80.

[11] Wohlgemuth M, van der Kooi EL, van Kesteren RG, et al. Ventilatorysupport in facioscapulohumeral muscular dystrophy. Neurology2004;63:176–8.

[12] Phillips MF, Steer HM, Soldan JR, et al. Daytime somnolence inmyotonic dystrophy. J Neurol 1999;246:275–82.

[13] Rubinsztein JS, Rubinsztein DC, Goodburn S, Holland AJ. Apathy andhypersomnia are common features of myotonic dystrophy. J NeurolNeurosurg Psychiatry 1998;64:510–5.

[14] MacDonald JR, Hill JD, Tarnopolsky MA. Modafinil reducesexcessive somnolence and enhances mood in patients with myotonicdystrophy. Neurology 2002;59:1876–80.

[15] Barbe F, Quera-Salva MA, McCann C, et al. Sleep-related respiratorydisturbances in patients with Duchenne muscular dystrophy. EurRespir J 1994;7:1403–8.

[16] Coccagna G,MantovaniM, Parchi C, et al. Alveolar hypoventilation andhyperosmnia in myotonic dystrophy. J Neurol Neurosurg Psychiatry1975;38:977–84.

[17] Dohna-Schwake C, Ragette R, Mellies U, et al. Respiratory function incongenital muscular dystrophy and limb girdle muscular dystrophy 2I.Neurology 2004;62:513–4.

[18] Sivak ED, Shefner JM, Sexton J. Neuromuscular disease andhypoventilation. Curr Opin Pulm Med 1999;5:355–62.

[19] Suresh S, Wales P, Dakin C, et al. Sleep-related breathing disorder inDuchenne muscular dystrophy: disease spectrum in the paediatricpopulation. J Paediatr Child Health 2005;41:500–3.

[20] Bushby KM, Pollitt C, Johnson MA, et al. Muscle pain as a prominentfeature of facioscapulohumeral muscular dystrophy (FSHD): fourillustrative case reports. Neuromuscul Disord 1998;8:574–9.

[21] Padberg GW, Lunt PW, Koch M, Fardeau M. Diagnostic criteria forfacioscapulohumeral muscular dystrophy. Neuromuscul Disord1991;14:231–4.

[22] Deidda G, Cacurri S, Piazzo N, Felicetti L. Direct detection of 4q35rearrangements implicated in facioscapulohumeral muscular dystrophy(FSHD). J Med Genet 1996;33:361–5.

[23] Cacurri S, Piazzo N, Deidda G, et al. Sequence homology between4qter and 10qter loci facilitates the instability of subtelomeric KpnIrepeat units implicated in facioscapulohumeral muscular dystrophy.Am J Hum Genet 1998;63:181–90.

[24] Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh SleepQuality Index: a new instrument for psychiatric practice and research.Psychiatry Res 1989;28:193–213.

[25] De Gennaro L, Martina M, Curcio G, Ferrara M. The relationshipbetween alexithymia, depression, and sleep complaints. Psychiatry Res2004;128:253–8.

[26] Vignatelli L, Plazzi G, Barbato A, et al. GINSEN (Gruppo ItalianoNarcolessia Studio Epidemiologico Nazionale). Italian version of theEpworth Sleepiness Scale: external validity. Neurol Sci 2003;23:295–300.

[27] Gordon N. Sleep apnoea in infancy and childhood. Considering twopossible causes: obstruction and neuromuscular disorders. Brain Dev2002;24:145–9.

[28] Gozal D. Pulmonary manifestations of neuromuscular disease withspecial reference to Duchenne muscular dystrophy and spinal muscularatrophy. Pediatr Pulmonol 2000;29:141–50.

[29] Laberge L, Begin P, Montplaisir J, Mathieu J. Sleep complaints inpatients with myotonic dystrophy. J Sleep Res 2004;13:95–100.

[30] Di Lazzaro V, Oliviero A, Tonali PA, et al. Changes in motor cortexexcitability in facioscapulohumeral muscular dystrophy. NeuromusculDisord 2004;14:39–45.