barrel chest

Neuraminidase Deficiency

Clinical Characteristics
Ocular Features: 

A cherry red spot is may be seen in late childhood or early adolescence.  It occurs in nearly 100% of patients with type I while only 75% of type II patients have this feature possibly because their early death from the more severe systemic disease prevents full ascertainment.  Visual acuity is reduced, sometimes severely.  Some but not all individuals have corneal and lens opacities.  A subtle corneal haze has also been seen.  Nystagmus has been reported. 

Systemic Features: 

This is a neurodegenerative disorder with progressive deterioration of muscle and central nervous system functions.  Myoclonus, mental deterioration, hepatosplenomegaly, muscle weakness and atrophy are common.  The defect in neuraminidase activity leads to abnormal amounts of sialyl-oligosaccharides in the urine.  Spinal deformities such as kyphosis are common.  Deep tendon reflexes are exaggerated.  Ataxia and hearing loss may be present.  Coarse facies, a barrel chest, and short stature are characteristic.  Hepatic cells contain numerous vacuoles and numerous inclusions.

Sialidosis types I and II are both caused by mutations in the neuroaminidase gene.  Type I is associated with milder disease than type II which has an earlier age of onset and may present in infancy or even begin in utero.  Early death within two years of age is common in the congenital or infantile forms.  There is, however, significant variability in age of onset and the course of disease among types. 

Genetics

The sialidoses are autosomal recessive lysosomal storage disorders resulting from mutations in the NEU1 gene (6p21.3) which lead to an intracellular accumulation of glycoproteins containing sialic acid residues.  Both types I and II are caused by mutations in the same gene. 

Treatment
Treatment Options: 

Treatment is focused on symptom management. 

References
Article Title: 

Spondyloepiphyseal Dysplasia Congenita

Clinical Characteristics
Ocular Features: 

Patients characteristically have vitreous abnormalities described as veils or stands.  The central vitreous may undergo liquefaction and the peripheral vitreous sometimes creates traction on the retina.  High myopia with progression is common and a significant proportion of patients suffer detachments of the retina even in the absence of myopia.  Lattice degeneration is frequently seen.  Most patients have 20/50 or better vision.

Systemic Features: 

Dwarfism with kyphosis and a barrel chest are characteristic.  The vertebrae are often flattened and malformed and the neck is short.  Delayed ossification in the epiphyses and the os pubis is common.  The disorder can be evident at birth but the full syndrome may not be evident until 3 or 4 years of age.  Radiologic studies are important in making the diagnosis.

Genetics

This is generally considered an autosomal dominant disorder secondary to mutations in the COL2A1 gene impacting type II collagen.  This type of collagen is found primarily in cartilage and vitreous and a number of type II collagenopathy disorders are associated with vitreoretinopathy and joint disease of which Stickler syndrome type I (609508, 108300) is the most common.  Other disorders in this database caused by mutations in COL2A1 are: Kniest dysplasia (156550), Stickler syndromes type I (609508, 108300 ) and II (604841), vitreoretinopathy with epiphyseal dysplasia (120140), and spondyloepiphyseal dysplasia congenita (183900).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Cervical fusion is sometimes used when odontoid hypoplasia leads to hypermobility of the cervical vertebrae.  Retinal detachments, of course, need to be repaired.

References
Article Title: 
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