Otospondylomegaepiphyseal Dysplasia

Disease with peculiar facies and severe degenerative joint disease of the osteoarthritis type affecting predominantly the hips, knees, elbows, and shoulders.

Nance Insley Syndrome; Nance Sweeny Chondrodysplasia; Chondrodystrophy with Sensorineural Deafness; OSMED.

Unknown.

Autosomal recessive and dominant forms exist. The responsible gene is located on 6p21.3.

Otospondylomegaepiphyseal dysplasia (OSMED) is a type XI collagenopathy with mutations in the procollagen XI genes (COL11A1 and COL11A2). However, the exact pathomechanism remains unclear.

Based on the clinical association of peculiar facies (hypoplastic midface with short, upturned nose having depressed nasal bridge, prominent eyes, and prominent supraorbital ridges), progressive sensorineural deafness, and severe degenerative joint disease of the osteoarthritis type predominantly affecting the hips, knees, elbows, and shoulders.

Can involve head and neck (mandibular hypoplasia, Pierre-Robin sequence [micrognathia, glossoptosis, cleft palate/uvula], flattened nose and cheek bones, anteverted nares), limbs (shortening of the long bones, short fingers, and metacarpals, fusion of the carpal bones, restricted joint mobility, metaphyseal flaring, large tarsal bones, prominent interphalangeal joints), and axial skeleton (enlarged odontoid in childhood, platyspondyly, anterior vertebral wedging, coronal vertebral clefts, kyphosis, scoliosis, square iliac wings). Other features may include ventricular septal defect, recurrent lower respiratory tract infections, hemangiomas, and lacrimal duct abnormalities.

If cardiac disease is suspected, evaluate cardiac function (clinically, ECG, echocardiogram). Assess for signs of difficult airway management. If kyphosis/scoliosis is severe, obtain lung function tests and chest radiograph.

Features of the disease suggest that direct laryngoscopy and tracheal intubation may be difficult. Special precautions against corneal injury should be taken in the presence of prominent eyes and lacrimal duct abnormalities. Patient may have ventricular septal defect, which requires specific anesthesia precautions. Vascular access and patient positioning may be difficult because of joint contractures.

Avoid neuromuscular blockers and maintain spontaneous ventilation until the airway has been secured. Subacute bacterial endocarditis prophylaxis may be indicated in the presence of a cardiac lesion.

OSMED is allelic with Stickler syndrome and Weissenbacher-Zweymüller syndrome.

Stickler Syndrome: Autosomal dominant inherited disorder most often caused by mutation in the COL2A1 gene; mutations in the COL11A1 and COL11A2 are less common. The pathognomonic feature is an vitreous gel architecture, which is associated with high, congenital, and nonprogressive myopia and a significantly increased risk of rhegmatogenous (associated with retinal tears) retinal detachment. Other signs include midface hypoplasia, flat nasal bridge, short nose with anteverted nares, micrognathia, and cleft palate. Joint hypermobility usually improves with age, whereas degenerative osteoarthritic symptoms (mainly hip and knee) are progressive and become manifest in the third or fourth decade of life. Conductive (secondary to cleft palate with chronic otitis media) but predominantly sensorineural hearing loss is common. Patients are most often mentally normal and of normal height. Mitral valve prolapse syndrome (Barlow Syndrome) has been reported to be a common finding (patients may require subacute bacterial endocarditis prophylaxis if thickened leaflets or signs of regurgitation are present).

Weissenbacher-Zweymüller Syndrome (Pierre-Robin Syndrome with Fetal Chondrodysplasia): Micrognathia and rhizomelic chondrodysplasia with enlargement of the epiphyses and metaphyses of the long bones resulting in a typical dumbbell shape (especially of humeri and femora) are the hallmarks of this autosomal recessive inherited syndrome. However, the overall changes are milder than those observed in OSMED and tend to resolve with increasing age, with impressive catch-up growth finally resulting in normal adult height. Midface hypoplasia, eye (optic nerve hypoplasia, severe myopia, retinal detachment) and ear (sensorineural hearing loss) anomalies, vertebral coronal clefts, and meningoceles/encephaloceles have been described in some patients. Psychomotor development is often delayed.

Marshall Syndrome: Autosomal dominant inherited disorder characterized by cataracts, myopia, abnormal vitreous, hypertelorism, midfacial hypoplasia, and congenital deafness. Some researchers consider Stickler and Marshall syndromes to be distinct entities, whereas others believe they are basically the same disease. This issue has not been resolved. Cleft palate is not as common in Marshall syndrome as in Stickler syndrome. In Marshall syndrome, the midface is described as flat with an upturned nose and large eyes; in Stickler syndrome, the face is rather long and flat with depressed nasal bridge.

Wagner Syndrome: Characterized by several optical malformations (e.g., ensheathed retinal vessels, retinal pigmentation, circular membranes in a liquefied vitreous, choroidal atrophy) with progressive clinical course ending with optic atrophy and blindness. In contrast to Stickler syndrome, retinal detachment is not a typical finding.