CMD
Diagnosis/testing
Diagnosis is based on clinical and radiographic findings of diffuse hyperostosis of the cranial base, cranial vault, facial bones, and mandible as well as widening and radiolucency of metaphyses in long bones.
Verification by genetic testing is recommended as CMD is part of a spectrum of craniotubular disorders, especially if clinical features are inconclusive.
Management
• Treatment for feeding and respiratory issues due to nasal obstruction may be needed in infants
• Progression of cranial hyperostosis and blood parameters should be regularly monitored
• Alkaline phosphatase, Ca, P, and PTH levels should be monitored
• Regular monitoring of vision, hearing, and for impaction of craniofacial foramina
• Surgical intervention to reduce compression of cranial nerves and the brain stem / spinal cord at the level of the foramen magnum
• Severely overgrown facial bones can be contoured; however, surgical procedures can be technically difficult and bone regrowth is common
• Hearing aids; vision aids and surgical treatment for optic nerve impaction; speech therapy; surgical intervention for malocclusion
• Monitoring of tooth eruption as teeth may be impacted or erupting late; orthodontic treatment
Surveillance
• Regular evaluation for feeding and respiratory issues in infants
• Neurologic evaluation for signs and symptoms of narrowing of the cranial foramina including the foramen magnum at least annually
• Hearing and ophthalmologic assessment at least annually
Other treatment
• Calcitriol treatment and low calcium diet were reported but some improvements that were seen may not be related to the treatment
CCAL2
Diagnosis/Testing
Acute attacks of joint pain, particularly in joints atypical for osteoarthritis, warrant radiologic evaluation. CPP crystals can usually be visualized in affected joints. Ultrasonography may also aid in the clinical diagnosis of CPP deposition, as well as computed tomographic (CT) scanning. Nevertheless, the gold standard for the definitive diagnosis of CPP deposition is examination of synovial fluid for the presence of positively birefringent, rhomboid-shaped crystals in affected joints. Using polarized microscopy with a red filter, the CPP crystals appear blue or yellow, depending upon their orientation with respect to the polarizer. CPP crystals are distinct from monosodium urate crystals in gouty synovial fluids in both color with respect to the polarizer and shape.
Final verification of CCAL2 in families with heritable cases of CPP disease requires genetic testing of the ANKH gene. CCAL2 mutations appear to reside in the amino terminal end of the ANKH protein. It should be noted that not all families suffering from CPP disease display mutations in ANKH. A second locus for the disorder, known as CCAL1, has been identified on chromosome 8q, and mutation at the termination codon of the gene that encodes osteoprotegerin has been identified in at least three families suffering from AD CPP disease.
Management
• Intraarticular glucocorticoids (reduction of inflammation)
• Oral colchicine (for patients without hepatic or renal issues; may reduce attack frequency)
• NSAIDS (reduction of inflammation)
• IL-1beta inhibitors (used in patients with refractory disease)
• Low dose oral glucocorticoids
• Hydroxychloroquine
• Methotrexate (in patients for whom other therapies have failed)
Surveillance
• Because there are no specific treatments for CCAL2, patients may need to be treated with a variety of agents, with periodic evaluation for efficacy and potential side effects.
Other Treatment
• Need for more controlled clinical trials of agents such as probenecid (anion channel inhibitor; commonly used for the treatment of gout)
ANKH