AD-CMD
AD-CMD is a rare craniotubular bone disorder with only a few hundred cases published worldwide. Inheritance is autosomal dominant with mutations in the ANKH gene. About 40% of patients known to the moderators carry de novo mutations.
Characteristic for AD-CMD is the progressive diffuse hyperostosis of cranial bones, which can already be detected in infancy. First diagnosis is often due to nasal obstruction or choanal stenosis, which result in feeding issues within a few months after birth. Also visible early on is a wide nasal bridge, paranasal bossing, widely spaced eyes (hypertelorism) and in some cases signs of facial palsy develop.
Development of dentition may be delayed and teeth may fail to erupt as a result of hyperostosis and sclerosis of alveolar bone. Progressive thickening of craniofacial bones continues throughout life, which leads to a characteristic facial expression with massive mandibles, paranasal bossing and hypertelorism with and increased zygomatic width. Hyperostosis of craniofacial bones often results in narrowing of cranial foramina, including the foramen magnum. If untreated, compression of cranial nerves can lead to disabling conditions such as facial palsy, blindness, or deafness (conductive and/or sensorineural hearing loss). Foramen magnum encroachment can result in Chiari malformation (type 1), which can result in syringomyelia and severe headaches. Headaches are often reported by patients.
Long bones are abnormally shaped, especially characteristic for AD-CMD is the flaring of femoral and tibial metaphyses. In contrast to cranial bones, long bone metaphyses are under-trabeculated and appear radiographically radiolucent. Cortical bone usually does not appear sclerotic.
Life expectancy is normal in individuals with typical uncomplicated AD-CMD; in those with severe AD-CMD life expectancy can be reduced as a result of compression of the foramen magnum.
CCAL2
AD-CCAL2 is a rare familial disorder characterized by the deposition of crystals of calcium pyrophosphate (CPP) in joints. When it presents as a heritable condition, it may occur as early as the second decade of life and frequently begins as an acute attack of joint pain and inflammation, commonly known as pseudogout. Fewer than 100 families have been reported to suffer from CPP disease as a heritable trait worldwide.
In families suffering from CCAL2, the most frequent presentation of disease is acute joint pain. The knee is most commonly affected, but the disease often displays a pattern of joint involvement that is distinct from osteoarthritis, affecting the wrist, the glenohumeral joint, and the metacarpophalangeal joints. In CCAL2 sufferers, it is not uncommon for CPP crystal deposition to precede frank joint degeneration. Joints that are affected by CPP crystals display a potent inflammatory response to the presence of the crystals, with warmth, redness and swelling, not unlike the response of joints that are infiltrated with monosodium urate crystals in gout. Patients may also complain of systemic symptoms including fever and chills. Unlike gout, acute attacks of CPP disease may last for weeks to months.
Other clinical presentations of AD-CCAL2 may occur, including a more chronic form of the disease that affects multiple joints. CPP crystals may also deposit in soft tissues, including spinal tissues, where tissue damage may be substantial.
Life expectancy is not compromised in CCAL2 patients, but quality of life is likely to be severely curtailed.
ANKH