A Familial Case of Multicentric Carpotarsal Osteolysis Syndrome and Treatment Outcome

Abstract

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder caused by heterozygous mutations in the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B). This is an autosomal dominant condition with a high frequency of sporadic cases. MCTO is characterized by osteolysis of the carpal, metacarpal, and tarsal bones beginning in early childhood with musculoskeletal rheumatologic symptoms such as pain and disability. Renal involvement can be seen in more than half of the patients; from ages 16 months to 42 years and manifests from proteinuria to end-stage renal failure requiring renal transplantation. The association of MAFB gene mutations with this genetic condition has aided in understanding the pathophysiology of the disease. We report here a 7-year-old Caucasian boy and his 33-year-old mother diagnosed with MCTO, with the boy having concomitant juvenile idiopathic arthritis. He was initially diagnosed with arthritis at age 5 years based on bilateral wrist synovial swelling, morning stiffness, and weakness with family history of his mother being diagnosed with erosive psoriatic arthritis leading to limb deformities. Initial therapy for the boy included methotrexate and infliximab with moderate response. Later, during the course of his disease, he underwent a genetic evaluation at age 7 years for history of learning disabilities and dysmorphic features. Maternal evaluation and radiographic examination led to a clinical diagnosis of MCTO in the mother, and subsequent testing for MAFB gene in the son revealed a mutation at c.206C > T (p.Ser69Leu), the most commonly reported genetic change in MCTO. Nevertheless, further imaging still confirmed ongoing arthritis, and therapy was adjusted based on its progression including abatacept, tocilizumab, and pamidronate. Our report highlights the possibility of concomitant inflammatory arthropathy in MCTO.

Keywords: inflammatory process; nephropathy; osteoclast; osteolysis.

Fig. 1

Anteroposterior view of the patient at age 7 showing triangular face, exophthalmos, downslanting palpebral fissures, slim nose, small mouth, downturned corners of the mouth, and micrognathia.

Fig. 2

X-ray of both wrists of our patient at 6 years of age showed severe deficiency of ossified carpal bones with only small portions of the distal row of carpal bone being visible, and erosive changes in the distal radial epiphysis bilaterally. Deformities of the proximal ends of the metacarpals were noted.

Fig. 3

( A ) Anteroposterior view of the patient's mother at age 33 showing hypertelorism, triangular facies, bulbous nose, hypoplastic nares, prominent columella, micrognathia, and chin dimple; ( B ) View of both hands of the same patient showing deformities and ulnar deviation of both wrists, elbow deformities, skin dimple at metacarpophalangeal joints, and deformities of fingers; ( C ) View of both feet of the same patient showing bilateral deformities in both feet and toes.

Fig. 4

( A ) Hand and forearm radiographs of the mother at age 33 revealed ulnar deviation of the wrists, absent carpal, and proximal metacarpal bones; proximal metacarpal bones are eroded and tapered; interphalangeal joints are distorted; ( B ) Elbow radiographs of the same patient revealed deformities.

Fig. 5

Anteroposterior ( A ) and lateral ( B ) view of both feet revealed marked osteolysis, dysplastic changes, and narrowed joint space of tarsal bones.