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Journal of the American Academy of Dermatology
Volume 41, n° 6
pages 950-956 (décembre 1999)
Doi : 10.1016/S0190-9622(99)70252-5
accepted : 4 June 1999
Epidermolysis bullosa simplex associated with muscular dystrophy: Phenotype-genotype correlations and review of the literature

Hiroshi Shimizu, MDa, Yasuko Takizawa, MVSa, Leena Pulkkinen, PhDb, Satoru Murata, MDc, Mitsuru Kawai, MDd, Hiroshi Hachisuka, MDe, Masako Udono, MDf, Jouni Uitto, MDb, Takeji Nishikawa, MDa
Tokyo, Minamikawachi-Machi, Shimoshizu, Kurume, and Nagasaki, Japan; and Philadelphia, Pennsylvania 
From the Department of Dermatology, Keio University School of Medicine, Tokyo,a the Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, Philadelphia,b the Department of Dermatology, Jichii Medical School, Minamikawachi-Machi,c the Department of Internal Medicine, Shimoshizu Hospital,d the Department of Dermatology, Kurume University School of Medicine,e and the Department of Dermatology, Nagasaki University School of Medicine.f 


Background: Epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD; OMIM# 226670) is an autosomal recessive disorder caused by genetic defects in the plectin gene. Because EBS-MD is relatively rare, and gene defects have been elucidated only in a limited number of patients, the precise phenotype-genotype correlations have not yet been fully elucidated. Objective: The purpose of this study was to define clinical features of EBS-MD and to clarify its phenotype-genotype correlations. Methods: Clinical, ultrastructural, immunohistochemical, and molecular features of 4 unrelated Japanese patients with EBS-MD were recorded. In addition, 6 cases with defined plectin gene mutations reported in the literature were reviewed. Results: In skin of the EBS-MD patients, the blister formation always occurs just above the hemidesmosomes, and expression of plectin is absent or markedly reduced in all cases examined. All 10 patients, including 6 cases in the literature, showed generalized blistering at birth or soon thereafter, and experienced nail deformities. In addition, decayed teeth (5 cases), urethral strictures (3), mild palmoplantar hyperkeratosis (2), infantile respiratory complications (2), alopecia (1), and laryngeal webs (1) were present. All 8 patients who were older than 9 years demonstrated considerable muscle weakness, and the majority of them ended up being wheelchair bound. Among the 10 patients, 7 were products of consanguineous marriage, 9 have premature termination codon (PTC) mutations in both alleles of the plectin gene, and 7 cases were homozygous for the mutation. One patient who is homozygous for a 2719del9 in-frame deletion mutation that resulted in elimination of 3 amino acids, QEA, could still walk at the age of 46 and showed milder clinical severity. Conclusion: EBS-MD reveals clinical features not only characteristic of EBS and MD, but also other manifestations including urethral, dental, and respiratory complications. The majority of patients are products of consanguineous marriage and have homozygous plectin gene mutations. Whereas patients with PTC mutations in both alleles typically showed severe clinical features of EBS-MD and ended up being wheelchair bound, a homozygous patient for an in-frame deletion mutation showed positive, yet attenuated, plectin expression and milder clinical phenotype. Thus plectin immunofluorescence, combined with identification of the underlying plectin mutations, is of value in predicting the severity of the muscle involvement that occurs later in life of patients with EBS-MD. (J Am Acad Dermatol 1999;41:950-6.)

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 Supported by Grants-in-Aid for Scientific Research (Nos. 05404036 and 07457191) from the Ministry of Education, Science, and Culture of Japan (H. S.), Keio Gijuku Academic Development Funds (H. S.), and US Public Health Service, National Institutes of Health grant PO1-AR38923 (J. U.). The mutation analyses were performed in the DebRA Molecular Diagnostics Laboratory at Jefferson Institute of Molecular Medicine, supported by the Dystrophic Epidermolysis Bullosa Research Association of America.
 Reprint requests: Hiroshi Shimizu, MD, PhD, Department of Dermatology, Hokkaido University School of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo 060-8638 Japan.
 0190-9622/99/$8.00 + 0  16/1/100407

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