odontoid hypoplasia

Morquio Syndrome (MPS IVB)

Clinical Characteristics
Ocular Features: 

Corneal clouding may not be seen until 10 years of age and is sometimes associated with photophobia.  The stroma has fine dust-like particles most dense centrally.  Penetrating keratoplasty is rarely indicated. There is little retinal degeneration unlike that often seen in other mucopolysaccharidoses but the corneal clouding often precludes detailed examination.

Systemic Features: 

This form of mucopolysaccharidosis is characterized by the urinary excretion of keratin sulfate.  Age of onset is highly variable but most children are diagnosed by 6 years of age.  It is a milder disease than the somewhat similar but genetically distinct Morquio type A (253000)  disorder.  Intelligence is normal and there is no central nervous system involvement.  Hip joints are dysplastic and frequently painful.  Vertebral malformations lead to kyphoscoliosis and short trunk dwarfism.  Odontoid hypoplasia can cause cervical instability and increases the risk of myelopathy with secondary bowel and bladder dysfunction.  Coxa valgum, and narrow phalanges are common.  Many individuals have a characteristic gait secondary to genu valgum.  Patients with MPS IVB initially do not have the coarse facies seen in some other forms of MPS.  Further accumulation of cellular keratin sulfate may lead to some coarsening of facial features, increased corneal clouding, and hepatomegaly.  Some form of hearing loss is common.

Genetics

This is an autosomal recessive lysosomal storage disease caused by a mutation in the GLB1 gene (3p21.33) encoding beta-galactosidase.  It is allelic to GM1 gangliosidosis (230500).  Type A Morquio syndrome (253000) is a separate disorder secondary to a mutation in a different gene.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

A variety of treatments are under investigation including enzyme replacement, gene therapy, and bone marrow transplantation.  Supportive and palliative measures for respiratory difficulties and skeletal deformities can be used.  Atlantoaxial subluxation is a constant risk and some physicians recommend prophylactic vertebral fusion.  Intubation for general anesthesia carries special risks.

References
Article Title: 

Mucopolysaccharidoses and the eye

Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol. 2006 Jan-Feb;51(1):1-17. Review.

PubMed ID: 
16414358

Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B

Paschke E, Milos I, Kreimer-Erlacher H, Hoefler G, Beck M, Hoeltzenbein M, Kleijer W, Levade T, Michelakakis H, Radeva B. Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Hum Genet. 2001 Aug;109(2):159-66.

PubMed ID: 
11511921

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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