Publications by authors named "Sabine Dittner-Moormann"

4 Publications

  • Page 1 of 1

Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria.

Cancers (Basel) 2021 Apr 14;13(8). Epub 2021 Apr 14.

Institute of Human Genetics, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.
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April 2021

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

Pediatr Blood Cancer 2021 Jun 15;68(6):e28963. Epub 2021 Mar 15.

The Goldschleger eye institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.

Introduction: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment.

Method: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication.

Results: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy.

Conclusion: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.
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June 2021

13q deletion syndrome resulting from balanced chromosomal rearrangement in father: the significance of parental karyotyping.

Mol Cytogenet 2020 23;13:31. Epub 2020 Jul 23.

Institute of Human Genetics, University Hospital Essen, Essen, Germany.

Background: Retinoblastoma is a malignancy of the eye in children characterized by biallelic inactivation of gene (), located at chromosome 13q14.2. Children with interstitial chromosome 13q deletions that include the gene show a predisposition to develop retinoblastoma and variable other features. Large 13q deletions with severe clinical phenotype are nearly always the result of a de novo mutation, i.e. the pathogenic alteration is not detected in parents. This results in a low risk for siblings to develop 13q deletion syndrome.

Result: Here, we describe a patient with profound muscle hypotonia, severe developmental delay and bilateral retinoblastoma carrying a large deletion in 13q13.3q14 with the size of 16 Mb, involving the gene. Neither parent showed retinoblastoma, muscle hypotonia or developmental delay. Chromosome analysis and Fluorescence in situ hybridization (FISH) showed a balanced complex chromosomal rearrangement (CCR) between chromosome 12 and 13 [ins(12;13)(q21.2;q12.3q14.3)] and an additional balanced translocation of chromosome 7 and 15 [t(7;15)(q31.2;q25.3)] in the healthy father. Malsegregation of the paternal insertional translocation involving chromosome 12 and 13 resulted in a 13q deletion syndrome of the child [46,XY,ins(12;13)(q21.2;q12.3q14.3)].

Conclusion: Balanced translocations in parents are a rare cause of de novo deletions in offspring. This case report emphasizes the need for parental chromosomal analysis and FISH in parents of children diagnosed with 13q deletion syndrome or large gene deletions to precisely determine the recurrence risk in siblings. Guidelines for genetic testing should be revised accordingly.
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July 2020

TRAPγ-CDG shows asymmetric glycosylation and an effect on processing of proteins required in higher organisms.

J Med Genet 2021 03 24;58(3):213-216. Epub 2020 Apr 24.

Department of Pediatrics, Universitätsklinikum Münster, Münster, Germany

Newly synthesised glycoproteins enter the rough endoplasmic reticulum through a translocation pore. The translocon associated protein (TRAP) complex is located close to the pore. In a patient with a homozygous start codon variant in TRAPγ (SSR3), absence of TRAPγ causes disruption of the TRAP complex, impairs protein translocation into the endoplasmic reticulum and affects transport, for example, into the brush-border membrane. Furthermore, we observed an unbalanced non-occupancy of N-glycosylation sites. The major clinical features are intrauterine growth retardation, facial dysmorphism, congenital diarrhoea, failure to thrive, pulmonary disease and severe psychomotor disability.
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March 2021