foveal atrophy

Cone-Rod Dystrophy With Decreased Male Fertility

Clinical Characteristics
Ocular Features: 

Features of a cone dystrophy appear first followed by rod damage although the course of degeneration is variable.  Poor vision may be present in some individuals in the first years of life but has a later onset in others.  Evidence for rod dysfunction appears later in most patients.

A hyperfluorescent area centered on the fovea can often be seen although there may be patchy areas elsewhere in the fundus.  Foveal atrophy is present in individuals generally after the 5th decade of life. Full field ERG shows reduced or absent cone responses with variable rod responses with more pronounced changes in older individuals.  Variable pigmentation can be seen in the peripapillary area.

Systemic Features: 

The only systemic abnormality thus far identified is a reduction in sperm count and reduced motility.  The resulting loss of fertility, however, occurs only in male patients with truncating variants in TTLL5 and not in those with missense mutations according to the most recent studies.

Genetics

This autosomal recessive condition results from homozygous or compound heterozygous mutations in the TTLL5 gene (14q24.3).  TTLL5 is localized at the base of the spermatozoal axoneme and at the basal body of the cilia in photoreceptors.  

Interestingly, male mice with mutations in this gene have reductions in sperm motility with evident disruption in the formation of sperm tails.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility

Bedoni N, Haer-Wigman L, Vaclavik V, Tran HV, Farinelli P, Balzano S, Royer-Bertrand B, El-Asrag ME, Bonny O, Ikonomidis C, Litzistorf Y, Nikopoulos K, Yioti G, Stefaniotou M, McKibbin M, Ellingford J, Booth AP, Black G, Toomes C, Inglehearn CF, Hoyng CB, Bax N, Klaver CC, Thiadens AA, Murisier F, Schorderet DF, Ali M, Cremers FP, Andreasson S, Munier FL, Rivolta C. Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility. Hum Mol Genet. 2016 Aug 22. pii: ddw282. [Epub ahead of print].

PubMed ID: 
27554115

Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy

Sergouniotis PI, Chakarova C, Murphy C, Becker M, Lenassi E, Arno G, Lek M, MacArthur DG; UCL-Exomes Consortium, Bhattacharya SS, Moore AT, Holder GE, Robson AG, Wolfrum U, Webster AR, Plagnol V. Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy. Am J Hum Genet. 2014 May 1;94(5):760-9.

PubMed ID: 
244791901

Macular Dystrophy with Central Cone Involvement

Clinical Characteristics
Ocular Features: 

This is primarily a cone dystrophy but there is evidence of some rod damage in older patients.  A mild decrease in central acuity is noted by individuals in the third to sixth decades.  Slight pigmentary changes and color vision abnormalities can be documented with the onset of these symptoms and a bull's eye maculopathy and severe atrophy of the central fovea may be present. An enlarging central scotoma with normal periphery can sometimes be identified.  Other patients have an atrophic appearance to the peripapillary area with a pale optic disc.  ERG responses to full-field testing are normal but multifocal studies reveal severely reduced central responses.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

Compound heterozygosity for a missense mutation and a nonsense mutation in the MFSD8 gene (4q28.2) has been found among members of a Dutch sibship suggesting autosomal recessive inheritance.       

The same mutant gene has been identified in some patients with late infantile or early juvenile onset lysosomal storage disease known as neuronal ceroid lipofuscinoses (610951) in which there may be optic atrophy, attenuated retinal vessels, a pigmentary retinopathy, and severe vision loss.   However, it is of note that no members of the Dutch family with the macular cone dystrophy described here had extraocular manifestations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Retinal Cone Dystrophy 3B

Clinical Characteristics
Ocular Features: 

This is a degenerative disorder in which patients have a progressive deterioration of visual acuity and color vision.  Most patients have significant myopia.  Visual difficulties begin in early childhood with acuity of 20/100 or worse by the second decade of life.  Color vision deficits can be detected in the second decade but nyctalopia occurs later in young adults.  Photophobia is a prominent symptom.  The ERG shows reduced and delayed cone responses.  Rod responses to low intensity flashes are undetectable but increased stimulus intensity leads to an abrupt increase in amplitude, often exceeding the upper limits of normal.

The fundus appears normal in some patients but foveal or parafoveal atrophy, a macular bull’s eye, hyperfluorescence anomalies, and a generalized fine pigmentary retinopathy have been reported.  There may be some temporal pallor in the optic nerves.  Nystagmus and strabismus may be present.

Systemic Features: 

No systemic disease has been reported.

Genetics

This is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the KCNV2 gene (9p24.2).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is available for this dystrophy.  Low vision aids and tinted lenses may be helpful.

References
Article Title: 
Subscribe to RSS - foveal atrophy