Revesz syndrome revisited

Abstract

Background Revesz syndrome (RS) is an extremely rare variant of dyskeratosis congenita (DKC) with only anecdotal reports in the literature. Methods To further characterize the typical features and natural course of the disease, we screened the English literature and summarized the clinical and epidemiological features of previously published RS cases. In addition, we herein describe the first recorded patient in central Europe. Results The literature review included 18 children. Clinical features are summarized, indicating a low prevalence of the classical DKC triad. All patients experienced early bone marrow failure, in most cases within the second year of life (median age 1.5 years; 95% CI 1.4–1.6). Retinopathy occurred typically between 6 and 18 months of age (median age 1.1 years; 95% CI 0.7–1.5). The incidence of seizures was low and was present in an estimated 20% of patients. The onset of seizures was exclusively during early childhood. The Kaplan–Meier estimate of survival was dismal (median survival 6.5 years; 95% CI 3.6–9.4), and none of the patients survived beyond the age of 12 years. Stem cell transplantation (SCT) was performed in eight children, and after a median of 22 months from SCT four of these patients were alive at the last follow up visit. Conclusion RS is a severe variant of DKC with early bone marrow failure and retinopathy in all patients. Survival is dismal, but stem cell transplantation may be performed successfully and might improve prognosis in the future.

Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability

“…On the severe side of clinical presentation, the DC/TBD subtypes known as Hoyeraal-Hreidarsson (HHS) and Revesz syndromes (RS) have an early presentation of BMF accompanied by neurological impairment. Specifically, HHS is associated with neurological and immunological abnormalities as well as intrauterine growth restriction (IUGR) ( 119 – 121 ), whereas RS includes retinopathy, neurological anomalies, and IUGR ( 3 , 122 ).…”

“…Most persons with DC/TBD have no significant developmental delay or intellectual disability, but the severe phenotypes HHS and RS do. HHS neurological phenotype is associated with cerebellum hypoplasia, microcephaly, and neurodevelopmental disorder ( 119 – 121 ), whereas RS includes bilateral exudative retinopathy, intracranial calcifications, and neurodevelopmental disorder ( 3 , 122 ).…”

Multisystemic Manifestations in Rare Diseases: The Experience of Dyskeratosis Congenita

“…It is another infrequent variant of DC due to pathogenic variants in the TINF2 gene [ 39 ]. The representing symptoms are the presence of bilateral exudative retinopathy, which is associated in most cases with intracranial calcification, and the classic alterations of DC, such as early bone marrow failure [ 43 ] and mucocutaneous disease. Intrauterine growth retardation, cerebellar hypoplasia and developmental delay may also be present [ 42 ].…”

Functional interaction between compound heterozygous TERT mutations causes severe telomere biology disorder

“…3,4 In addition to those features, severe forms of the disease include Hoyeraal-Hreidarsson syndrome, characterized by growth restriction, microcephaly, cerebellar hypoplasia, immunodeficiency and developmental delay, 16,17 and Revesz syndrome, which is characterized by cerebral calcifications and exudative retinopathy. 18,19 The catalytic subunit of human telomerase, hTERT, is a reverse transcriptase that interacts stably with its template-containing RNA subunit, hTR. 20,21 hTERT catalyzes the addition of nucleotides to the 3 9 end of a single-strand telomeric DNA substrate; when the end of the short template sequence is reached, the RNA molecule translocates relative to the DNA molecule, positioning the substrate for another round of addition.…”