C21orf2

Retinal Dystrophy with or without Macular Staphyloma

Clinical Characteristics
Ocular Features: 

Few patients have had complete eye studies and physical findings are seemingly limited to the eye.  Patients complain of progressively decreasing vision as early as the first decade of life.  Abnormal retinal findings may be present by the second decade and maybe earlier.  The RPE can appear mottled and the retinal vessels are attenuated.  Retinal pigment clumping occurs later.  Night blindness and visual field constriction occur.  Cone and flicker ERGs may be nonrecordable while rod and flash ERGs are reduced consistent with a rod-cone dystrophy.  The retinal lamination has been described as abnormal on OCT in some individuals.

Macular staphylomas have been described in three unrelated offspring of consanguineous parents.

Vision loss is severe with legal blindness by midlife and one patient lost light perception by 40 years of age.  

Systemic Features: 

No consistent systemic abnormalities have been reported.

Genetics

Homozygous or compound heterozygous mutations in the C21orf2 gene (21q22.3) are the cause of this autosomal recessive syndrome.

Homozygous or heterozygous mutations in the same gene are responsible for axial spondylometaphyseal dysplasia (602271).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Spondylometaphyseal Dysplasia, Axial

Clinical Characteristics
Ocular Features: 

Due to the small number of individuals reported, the ocular phenotype is variable and likely incompletely described.  Optic atrophy and pigmentary retinopathy are the most consistent findings.  The most completely studied individual had evidence of slight bilateral optic nerve atrophy on cerebral MRI imaging as well.  There may be extensive RPE atrophy but the fundus pigmentation is usually described as resembling retinitis pigmentosa.  The ERG in several patients during the second decade of life already shows severe dysfunction of the photoreceptors, with cones the most severely impacted.  In spite of this Goldmann visual fields have been reported to be normal.  The macula and OCT have been reported as normal.  Telecanthus, nystagmus, hypertelorism, proptosis, and photophobia have been reported.  Early onset and progressive visual impairment are characteristic.

Systemic Features: 

Only 5 patients with this condition have been reported most of whom were short in stature.  There may be frontal bossing and the chest is narrow and flattened.  Moderate platyspondyly has been described with enlarged but shortened ribs and an irregular iliac crest.  Rhizomelic shortening of the limbs is common.  The femoral metaphyses are abnormal with their necks shortened and enlarged.  The ribs are enlarged but shortened as well and are flared at the ends.  Mental development and function are normal.

Genetics

This is an autosomal recessive condition due to homozygous or compound heterozygous mutations in C21orf2.

Treatment
Treatment Options: 

No effective treatment is known.

References
Article Title: 

Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations

Wang Z, Iida A, Miyake N, Nishiguchi KM, Fujita K, Nakazawa T, Alswaid A, Albalwi MA, Kim OH, Cho TJ, Lim GY, Isidor B, David A, Rustad CF, Merckoll E, Westvik J, Stattin EL, Grigelioniene G, Kou I, Nakajima M, Ohashi H, Smithson S, Matsumoto N, Nishimura G, Ikegawa S. Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations. PLoS One. 2016 Mar 14;11(13).

PubMed ID: 
26974433

Axial spondylometaphysealdysplasia

Ehara S, Kim OH, Maisawa S, Takasago Y, Nishimura G. Axial spondylometaphysealdysplasia. Eur J Pediatr. 1997 Aug;156(8):627-30.

PubMed ID: 
9266195
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