J Clin Neurol.  2017 Oct;13(4):405-410. 10.3988/jcn.2017.13.4.405.

Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture

• Lee Y
• Lee JH
• Park HJ
• Choi YC

• KMID: 2392137
• DOI: http://doi.org/10.3988/jcn.2017.13.4.405

Abstract

BACKGROUND AND PURPOSE
The early diagnosis of LMNA-associated muscular dystrophy is important for preventing sudden arrest related to cardiac conduction block. However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with later involvement of contracture and limb-girdle muscular dystrophy type 1B is often delayed due to heterogeneous clinical presentations. We aimed to determine the clinical features that contribute to a delayed diagnosis.
METHODS
We reviewed four patients who were recently diagnosed with LMNA-associated muscular dystrophy by targeted exome sequencing and who were initially diagnosed with nonspecific or other types of muscular dystrophy.
RESULTS
Certain clinical features such as delayed contracture involvement and calf hypertrophy were found to contribute to a delayed diagnosis. Muscle biopsies were not informative for the diagnosis in these patients.
CONCLUSIONS
Genetic testing of single or multiple genes is useful for confirming a diagnosis of LMNA-associated muscular dystrophy. Even EDMD patients could experience the later involvement of contracture, so clinicians should consider early genetic testing for patients with undiagnosed muscular dystrophy or laminopathy.

Keyword

lamin A/C; limb-girdle muscular dystrophy type 1B; emery-dreifuss muscular dystrophy

MeSH Terms

Biopsy
Contracture*
Delayed Diagnosis
Diagnosis
Early Diagnosis
Exome
Genetic Testing
Humans
Hypertrophy
Muscular Dystrophies*
Muscular Dystrophies, Limb-Girdle
Muscular Dystrophy, Emery-Dreifuss

Figure

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  Fig. 1 Histopathologic findings of a muscle biopsy. A, B, and C: A muscle biopsy specimen from patient 1 showed slight size variations in the muscle fibers and a few necrotic and degenerative fibers, suggesting mild myopathic changes. D: Emerin protein was detectable. A: Hematoxylin and eosin stain (×200), B: NADH stain (×200), C: modified Gomori trichrome stain (×200), D: Emerin immunohistochemistry (×200).

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  Fig. 2 Immunostaining of muscle biopsy specimens for lamin A/C (×200). Muscle biopsy specimens from patients 1 (A), 2 (B), and 3 (C) showed normal lamin A/C immunostaining compared to a normal healthy subject (D).

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