Muscular Dystrophy Associated WithExtra-Abdominal Desmoid Tumor ShowingAberrant Chromosome 1 [46,XX,add(1)(p36)]

Michihiko Katsuura,1* Mitsuhiro Kato,1 Dai Sendo,1 Kaori Akiba,1 Akira Honma,3Yumiko Takahashi,1 Chikahiko Numakura,1 Shinkichi Yokoyama,1 Ikuya Nonaka,4Takanori Shibata,2 and Kiyoshi Hayasaka1

1Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan2Department of Oral and Maxillofacial Surgery, Yamagata University School of Medicine, Yamagata, Japan3Yamagata Medical Rehabilitation Center for Disabled Persons, Yamagata, Japan4Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology andPsychiatry, Tokyo, Japan

We report on a 2-year-old girl with probablelimb-girdle muscular dystrophy associatedwith an extra-abdominal desmoid tumor ofthe right mandible. This association is pre-viously undescribed. The tumor was totallyremoved. Cytogenetic analysis of the tumorshowed a clonal karyotypic abnormality:46,XX,add(1)(p36) in 3 of 20 cells analyzed.Since an association of a neoplasm withlimb-girdle muscular dystrophy has previ-ously been reported in 3 cases, the two ab-normalities are likely related causally. Thechromosome abnormality in our patientmay play a role in the occurrence of herdesmoid tumor. Am. J. Med. Genet. 76:42–44,1998. © 1998 Wiley-Liss, Inc.

KEY WORDS: desmoid tumor; musculardystrophy; chromosome 1;chromosome abnormality

INTRODUCTION

Limb-girdle muscular dystrophy is a heterogenousgroup of diseases characterized by progressive weak-ness of the pelvic and shoulder girdle muscles [Menkes,1995]. Most patients show autosomal recessive inheri-tance, while a few show dominant inheritance. Severalgenes responsible for the disease have been mapped asfollows: the autosomal dominant form to 5q22-q34[Speer et al., 1992] and five autosomal recessive forms,respectively, to 2p13-p16 [Bashir et al., 1994], 4q12[Lim et al., 1995], 13q12 [Ben Othmane et al., 1992;

Azibi et al., 1993], 15q15.1 [Beckmann et al., 1991],and 17q12-q21.33 [Roberds et al., 1994]. The genes for3 of the 5 autosomal recessive forms have been identi-fied in sarcoglycan complexes [Ben Othmane et al.,1992; Azibi et al., 1993; Roberds et al., 1994; Lim et al.,1995] and muscle-specific calpain 3 genes [Richard etal., 1995]. Desmoid tumor is an uncommon fibroblasticproliferative lesion that originates from muscle or fas-cia. Although traumatic endocrine and genetic factorshave been thought to play a role in the desmoid tumorformation, recent cytogenetic analysis showed clonalchromosomal aberrations, indicating that the tumor isa neoplastic disease [Karlsson et al., 1988; Bridge et al.,1992].

We report here on a patient with limb-girdle muscu-lar dystrophy who had a benign extra-abdominal des-moid tumor with a chromosome abnormality.

CLINICAL FINDINGS

A 2-year-old girl was admitted to our hospital be-cause of a mass in her right jaw. She did not have painor fever. She was born by normal term delivery and didnot have any troubles in prenatal and perinatal peri-ods. Her 32-year-old father and 30-year-old motherwere healthy and non-consanguineous. On admission,she weighed 12 kg and was 81 cm long. She had nomuscle symptoms. The tumor was bony hard, measur-ing 2 × 4 cm in diameter with no skin lesions. No ab-dominal mass or lymph nodes were palpable. Therewas no change in a complete blood cell count. The fol-lowing serum enzyme levels were increased: aspartateaminotransferase of 62 IU/l (normal range: 22–27), ala-nine aminotransferase 45 IU/l (8–10), lactate dehydro-genase (LDH) 1,135 IU/l (220–420), creatine kinase(CK) 1,803 IU/l (33–165), and aldolase 23.8 IU/l (2.5–6.1). Isozyme analyses revealed a slight increase ofLDH 2 to 43% (30–40%) and a marked increase of CK-MB to 10.4% (1–4%). Erythrocyte sedimentation rate

*Correspondence to: Michihiko Katsuura, M.D., Department ofPediatrics, Yamagata University School of Medicine, Iida-nishi2-2-2, Yamagata 990-23, Japan.

Received 26 December 1996; Accepted 21 October 1997

American Journal of Medical Genetics 76:42–44 (1998)

© 1998 Wiley-Liss, Inc.

was 52 mm/hr (2–15). Focal bone destruction was de-tected in her right mandible by radiological examina-tions. Neck computed tomography scanning docu-mented a well-defined 3 × 2 × 2 cm mass with lowdensity at the lower margin of the right mandibularbody. Bone scintigraphy and gallium scintigraphy didnot show any radioactive accumulation in the mass.

She was suspected to have a rhabdomyosarcoma ormalignant lymphoma. The tumor partially adhered tobone was totally resected. From a histological finding ofspindle or polygonal cell proliferation with interveningthick collagen bundles but without cellular atypism,she was diagnosed as having an extra-abdominal des-moid tumor. Cytogenetic analysis of the resected tumortissue showed a clonal abnormality, 46,XX,add(1)(p36),in 3 of 20 cells analyzed and a normal 46,XX karyotypein the remaining cells (Fig. 1).

She continued to have high LDH and CK levels evenafter the tumor resection and was noticed to have in-creased calf muscle consistency and limitation of ankledorsiflexion. In the biopsied left gastrocnemius muscle,there were dystrophic changes with notable variationin fiber size, active necrotic and regenerating process,and moderate interstitial fibrosis. Two foci of mild andmarked mononuclear cell infiltration were seen in theinterstitium. The undifferentiated type 2C fibers wereincreased in number to 20%, reflecting an increasednumber of regenerating fibers. Dystrophin, a and b

sarcoglycan complexes (adhalin and 43KD), dystro-phin-associated glycoproteins (DAG), and merosinwere all detected immunohistochemically.

One year after surgery, she developed slowness inrunning and difficulty in climbing stairs. She showedmild Gowers’ sign and pseudohypertrophy of the gas-trocnemius. Because of the rapidly progressive clinicalsymptom and the focal mononuclear cell infiltration inthe muscle specimen, we could not rule out polymyosi-tis. While prednisolone was given orally, her clinicalsigns did not improve. She was diagnosed as havinglimb-girdle muscular dystrophy from the clinical andpathologic findings.

DISCUSSION

Although it remains uncertain whether neoplasmsare related to progressive muscular dystrophies, 6 pa-tients with such associations have been reported, in-cluding neuroblastoma [Johnston et al., 1986], rhabdo-myosarcoma [Komine et al., 1992], acute lymphoblasticleukemia [Svarch et al., 1988] in 3 patients with Du-chenne muscular dystrophy, and multiple myeloma in3 adults with limb-girdle muscular dystrophy [Kisslingand Michot, 1984]. An association of muscular dystro-phy with a desmoid tumor in our patient has not beenpreviously described. Cytogenetic analysis of the des-moid tumor revealed various karyotypic abnormalities[Karlsson et al., 1988; Bridge et al., 1992]. Structuralrearrangements of chromosome 1p have been detectedin leukemias and solid tumors [Dracopoli et al., 1994].Therefore, it is likely that there exists a locus impor-tant for the regulation of cellular growth on 1p ratherthan genes related to tumor suppression.

Limb-girdle muscular dystrophy is genetically heter-ogenous. It is no longer satisfactory to classify limb-girdle muscular dystrophies by phenotypic criteriaalone [Shields, 1994]. Recently, mutations in DAG andthe calpain-3 genes have been found in patients withautosomal recessive type of limb-girdle muscular dys-trophy [Roberds et al., 1994; Lim et al., 1995; Richardet al., 1995]. There have been no reports of patientswith progressive muscular dystrophy that is linked tochromosome 1. Although the relationship betweenmuscular dystrophy and the desmoid tumor with thechromosomal aberration in our patient is uncertain,further genetic studies are necessary to determinewhether the tumor formation is incidental or related tomuscular dystrophy.

ACKNOWLEDGMENTS

We are grateful to Prof. Masazumi Tsuneyoshi, TheSecond Department of Pathology, Kyushu UniversitySchool of Medicine, and to Dr. Mikio Matsuda, The Sec-ond Department of Pathology, Yamagata UniversitySchool of Medicine, for their help and invaluable ad-vice.

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