Cardiac involvement in facio-scapulo-humeral muscular dystrophy: a family study using Thallium-201 single-photon-emission-computed tomography

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Abstract

Fifteen persons from two consecutive generations of one family affected with facio-scapulo-humeral muscular dystrophy (FSHD) were clinically and neurophysiologically examined. Diagnostic muscle biopsies were obtained from two members. Linkage analysis showed that all four affected members of the family inherit the same 4q35 haplotype giving a lod score of z = +1.44. Six family members were examined by ECG at rest and under stress, by two-dimensional echocardiography, and by cardiac Thallium-201 single-photon-emission computed tomography (Tl-201-SPECT) under dobutamine stress and at rest. Abnormal reduced Tl-201 uptake in cardiac SPECT was only found in the affected members of the family. Therefore we suggest that cardiac Tl-201-SPECT abnormalities in FSHD reflect cardiomyogenic changes in this type of muscular disease.

Introduction

The myocardium is affected in malignant forms of muscular dystrophy (MD), and early functional disturbances have been detected in such patients (Nigro et al., 1990). Cardiac function may also be impaired in less severe muscle diseases (De Visser et al., 1992). Although cardiomyopathy is not part of the facio-scapulo-humeral muscular dystrophy (FSHD) (Padberg et al., 1991), cardiac involvement has been found in FSHD by means of electro-(ECG) and/or echocardiography in single cases (Welsh et al., 1963; Bloomfield and Sinclair-Smith, 1965; Caponnetto et al., 1968, Baldwin et al., 1973; Carrol, 1979) as well as in two studies (Stevenson et al., 1990; Berlit and Stegaru-Hellring, 1991). However, some of the reported cases of FSHD were probably cases of what has since been recognized as the phenotypically similar Emery-Dreifuss dystrophy (cf Stevenson et al., 1990). For this reason only genetically documented cases of FSHD should be studied with regard to the question of cardiac involvement. The FSHD gene has been localized to the subtelomeric region of the human chromosome 4, 4q35, by linkage analyses in affected families (Wijmenga et al., 1990).

Thallium-201 single-photon-emission computed tomography (Tl-201-SPECT) is a sensitive and efficient non-invasive method for detecting cardiac defects and/or dysfunctions (Burow et al., 1979; Holman et al., 1979; Ritchie et al., 1982). Tl-201-SPECT has shown cardiac abnormalities in MD, including FSHD (Yamamoto et al., 1988; Faustmann et al., 1990; Faustmann et al., 1992; Nagamachi et al., 1994). Yet in studies under physical exercise in which bicycle ergometers are employed, involvement of the pelvic girdle may influence the cardiac SPECT-results in MD (cf. Padberg et al., 1991), thus rendering them only partially valid (cf. Iskandrian et al., 1989). The use of pharmacological stress testing such as dobutamine has become an alternative approach for studying patients who are incapable of maximum physical performance (Mason et al., 1984).

In this study we investigated six members of a genetically identified family with dominantly inherited FSHD using cardiac Tl-201-SPECT under dobutamine stress and at rest.

Section snippets

Patients and methods

We studied 15 persons from 2 consecutive generations of one family (see pedigree in Fig. 1). In generation II four men (mean age 50.5 years, range 55–65 years), and in generation III six men and two women (mean age 31.6 years, range 27–37 years) were clinically examined: creatine kinase (CK) activities were determined, and concentric needle electromyographies (EMG) were carried out. Four members underwent additional nerve conduction studies (II,1; II,4; III,1; III,3); diagnostic muscle biopsies

Results

Affected members of the family with FSHD were identified by clinical, electrophysiological, and histopathological investigation and genetic linkage analysis. The median onset age was 35 years in generation II, and 30 years in generation III.

The clinical data and results of the additional examinations are summarized in Table 1.

The pedigree of the German family with autosomal dominant FSHD shows linkage to the D4S163, D4S139, D4F104S1 haplotype on chromosome 4q35 (Fig. 1). All affected

Discussion

Previous studies failed to provide a clear picture of the types and prevalence of cardiac involvement in FSHD (Baldwin et al., 1973; Berlit and Stegaru-Hellring, 1991; Bloomfield and Sinclair-Smith, 1965; Caponnetto et al., 1968; Carrol, 1979; Stevenson et al., 1990; Welsh et al., 1963; Yamamoto et al., 1988). Impairment of heart muscle function may occur in different ways: persistent atrial arrest (Baldwin et al., 1973; Bloomfield and Sinclair-Smith, 1965; Caponnetto et al., 1968), bundle

Acknowledgements

We wish to thank U. Mohrig and M. Otto, Marburg, and Schwester Rosemarie Lauer, Essen, for excellent technical assistance, and Gregor Weibels and Dr. Reinhard Ganz for critical comments. This study was supported by the P.E. Kempes Stiftung, Marburg and the Freunde und Förderer der Neurologischen Universitätsklinik Essen.

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