Alternative titles; symbols
SNOMEDCT: 723512008; ORPHA: 3088; DO: 0070026;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 14q12 | Revesz syndrome | 268130 | Autosomal dominant | 3 | TINF2 | 604319 |
A number sign (#) is used with this entry because of evidence that the Revesz syndrome is caused by heterozygous mutation in the TINF2 gene (604319) on chromosome 14q12.
Revesz syndrome is a severe autosomal dominant bone marrow failure and cancer predisposition syndrome that includes the classical dyskeratosis congenita triad of oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, with the additional feature of bilateral exudative retinopathy. Other features of Revesz syndrome include intrauterine growth retardation, intracranial calcification, and cerebellar hypoplasia (summary by Sasa et al., 2012).
For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).
Revesz et al. (1992) reported the case of a Sudanese male infant who was found to have bilateral exudative retinopathy at 6 months of age. A month later, severe aplastic anemia was found, which led to the child's death at the age of 19 months. The features of this syndrome were intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation. Kajtar and Mehes (1994) described similar findings in a 2-year-old Hungarian Gypsy girl who presented with thrombocytopenic purpura. Severe bone marrow hypoplasia was associated with bilateral progressive Coats retinopathy, nail dystrophy, fine hair, and apparent chromosome instability.
Savage et al. (2008) described a patient with Revesz syndrome who had the characteristic bilateral exudative retinopathy, the dyskeratosis congenita triad of nail dystrophy, skin hyperpigmentation, and oral leukoplakia, as well as developmental delay, cerebellar hypoplasia, and very short telomere lengths. Severe aplastic anemia developed at age 1.5 years. The patient died after bone marrow transplant. Savage et al. (2008) considered Revesz syndrome to be part of the DKC disease spectrum.
Sasa et al. (2012) reported a 21-month-old Hispanic boy with Revesz syndrome. He presented with severe aplastic anemia and was noted to have bilateral exudative retinopathy at age 9 months. He also had poor growth, nail dystrophy, oral leukoplakia, and delayed development with wide-based gait, suggesting cerebellar involvement. He underwent cord blood transplantation, but died 92 days later. Telomere lengths were shortened.
The heterozygous mutation in the patient with Revesz syndrome reported by Savage et al. (2008) occurred de novo.
In a patient with Revesz syndrome, Savage et al. (2008) identified a de novo heterozygous mutation in the gene encoding TRF1-interacting nuclear factor-2 (TINF2; 604319.0002), a component of the shelterin telomere protection complex. His unaffected parents and 1 sister had normal telomere lengths and no mutation in TINF2.
In a 21-month-old Hispanic boy with Revesz syndrome, Sasa et al. (2012) identified a heterozygous truncating mutation in exon 6 of the TINF2 gene (604319.0006). A truncated protein was expressed, but at lower levels than wildtype, suggesting decreased stability. The mother did not carry the mutation, but the father was unavailable for study.
Kajtar, P., Mehes, K. Bilateral Coats retinopathy associated with aplastic anaemia and mild dyskeratotic signs. Am. J. Med. Genet. 49: 374-377, 1994. [PubMed: 8160728] [Full Text: https://doi.org/10.1002/ajmg.1320490404]
Revesz, T., Fletcher, S., Al-Gazali, L. I., DeBuse, P. Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome? J. Med. Genet. 29: 673-675, 1992. [PubMed: 1404302] [Full Text: https://doi.org/10.1136/jmg.29.9.673]
Sasa, G. S., Ribes-Zamora, A., Nelson, N. D., Bertuch, A. A. Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood. Clin. Genet. 81: 470-478, 2012. [PubMed: 21477109] [Full Text: https://doi.org/10.1111/j.1399-0004.2011.01658.x]
Savage, S. A., Giri, N., Baerlocher, G. M., Orr, N., Lansdorp, P. M., Alter, B. P. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am. J. Hum. Genet. 82: 501-509, 2008. [PubMed: 18252230] [Full Text: https://doi.org/10.1016/j.ajhg.2007.10.004]