Unraveling melorheostosis: insights into clinical features, diagnosis, and treatment

Abstract

Melorheostosis is a rare bone disease characterized by abundant bone formation with a characteristic radiographic appearance that resembles "dripping candle wax." Recent data have shown that the majority of cases are due to somatic activating mutations in bone. Melorheostosis has several clinical and radiographic presentations, which are now known to be caused by different somatic mutations such as MAP2K1, SMAD3, KRAS, and LEMD3. This review provides a comprehensive look at the clinical features, diagnostic approaches, and current treatment options for melorheostosis, alongside future research directions aimed at improving patient outcomes.

Keywords: MAP2k1; SMAD3; genetics; osteoblasts; rare bone disease.

Figure 1

Clinical and radiographic appearance of classical melorheostosis. (A) Clinical photograph showing limb enlargement. (B) Lateral radiograph of the tibia shows flowing hyperostosis. (C) and (D) Increased uptake is seen in 18F-sodium fluoride PET scan. From Kang et al., used by permission.

Figure 2

Slow progression of melorheostosis. (A) Anterior-posterior radiograph of the shoulder shows increase in melorheostosis after 10 yr. (B) Lateral radiograph of hip shows increased in size and density of exostosis. From Jha et al., used by permission.

Figure 3

Histology of melorheostosis. (A) Woven bone and abundant osteoid seen in affected bone of melorheostosis. (B) Haversian canals have multiple arterioles. (C) Higher magnification view shows abundance unmineralized bone matrix. (D) Large number of osteoblasts (arrows) seen on endosteal surface. From Fick et al., used by permission.

Figure 4

Example of endosteal melorheostosis. (A) Anterior-posterior and (B) lateral radiograph of the tibia show bone formation on the endosteal surface. (C) CT scan further reveals the disorganized pattern. (D) Histological appearance is notable for thick cortical bone with no osteoid.

Figure 5

Radiographs of the (A) hip and (B) foot in a patient with osteopoikolosis and melorheostosis. LEMD3 germline mutation was confirmed on genetic testing.