Clinical Description
Individuals with Camurati-Engelmann disease (CED) present with limb pain, proximal muscle weakness, poor muscular development, a wide-based, waddling gait, easy fatigability, and headaches. The average age of onset of symptoms in the 306 reported individuals is 13.4 years [Carlson et al 2010] with a range from birth to age 76 years [Wallace et al 2004].
Musculoskeletal. Decreased muscle mass and weakness are most apparent in the proximal lower limbs, resulting in difficulty when rising from a sitting position. A wide-based, waddling gait is found in 48%-64% of individuals. Joint contractures occur in 43% of individuals. Marfanoid body habitus is described in some affected individuals [Wallace et al 2004, Janssens et al 2006]. Musculoskeletal involvement can lead to varying degrees of lumbar lordosis, kyphosis, scoliosis, coxae valga, radial head dislocation, genua valga, hallux valgus, flat feet, and frontal bossing [Yuldashev et al 2017].
Bone pain is reported in 68%-90% of affected individuals [Wallace et al 2004, Janssens et al 2006]. The reported severity of bone pain ranged from mild (not requiring any treatment) to severe (requiring narcotic analgesics) [Yuldashev et al 2017]. The pain is described as constant, aching, and most intense in the lower limbs. Pain often increases with activity, stress, and cold weather. Many individuals have intermittent episodes of severe pain and incapacitation. Bone pain has resulted in limited ambulation in some individuals. The enlarged bone shafts can also be palpable and tender on examination; 52% of affected individuals report bone tenderness with palpation [Wallace et al 2004]. Intermittent limb swelling, erythema, and warmth also occur.
Although bone mineral density measured at the hip and femoral neck are increased in individuals with CED, bone strength measured by bone impact microindentation in three sibs with CED was below normal. Because of the small sample size, the difference in bone strength was not statistically significant. [Herrera et al 2017]. Increased susceptibility to fracture has not been reported. Healing of fractures, when they occur, may be delayed [Wallace et al 2004].
Neurologic. Sclerosis of the cranial nerve foramina can lead to direct nerve compression or neurovascular compromise. Cranial nerve deficits occur in 38% of affected individuals. The most common deficits are hearing loss, vision problems, and facial paralysis.
Approximately 19% of individuals with CED have conductive and/or sensorineural hearing loss [Carlson et al 2010]. Conductive loss can be caused by narrowing of the external auditory meatus, bony encroachment of the ossicles, or narrowing of the oval and round windows. Sensorineural hearing loss is caused by narrowing of the internal auditory canal and compression of the cochlear nerve and/or vasculature. Sensorineural hearing loss can also occur with attempted decompression of the facial nerves.
Involvement of the orbit has led to blurred vision, proptosis, papilledema, epiphora, glaucoma, and subluxation of the globe [Carlson et al 2010, Popiela & Austin 2015].
Rarely, clonus [Neuhauser et al 1948], sensory loss, slurred speech, dysphagia, cerebellar ataxia, and bowel and bladder incontinence are reported [Carlson et al 2010]. Calvarial hyperostosis can lead to increased intracranial pressure and headaches.
Recurrent cranial hyperostosis following surgical decompression can occur [Wong et al 2017].
Facial features. Children with CED do not typically have recognizable changes to their facial features. In older individuals who are severely affected, osteosclerosis of the skull can lead to macrocephaly, frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy.
Ribbing disease, an osteosclerotic disease of the long bones that is radiographically indistinguishable from CED and usually presents with bone pain after puberty [Makita et al 2000], is now known to be caused by pathogenic variants in TGFB1 [Janssens et al 2006]. Thus, CED and Ribbing disease represent phenotypic variations of the same disorder.
Other. Rare manifestations include anemia (hypothesized to be caused by a narrowed medullary cavity), anorexia, low body mass index, hepatosplenomegaly, decreased subcutaneous tissue, atrophic skin, hyperhidrosis of the hands and feet, delayed dentition, extensive caries, delayed puberty, and hypogonadism [Gupta & Cheikh 2005, Yuldashev et al 2017].
Pregnancy. One individual who experienced relief with steroids also experienced decreased bone pain and improved muscle strength while pregnant, which allowed discontinuation of her steroid therapy. Scintigraphic bone imaging with methylene diphosphate (MDP) a few hours after delivery of her second child showed decreased uptake compared to imaging prior to pregnancy and six weeks post partum.