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Eur J Neurol. 2019 Dec 8. doi: 10.1111/ene.14138. [Epub ahead of print]

Pseudo-anticipation in Creutzfeldt - Jakob disease is Due to a Rhomboid Shaped Artifact.

Author information

1
Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel.
2
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
3
Barzilai Medical Center, Ashkelon, Israel.
4
Departments of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
5
The Department of Neurology, the Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
6
Department of Neurology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
7
Robert and Martha Harden Chair in Mental and Neurological Diseases, Sackler Faculty of Medicine, Tel Aviv University, Israel.

Abstract

BACKGROUND:

Previous studies reported conflicting results regarding possible anticipation in familial E200K Creutzfeldt-Jakob disease (fCJD).

OBJECTIVES:

To use a large database to assess age of disease onset (AODO) in CJD.

METHODS:

The study population included 477 CJD patients (266 with fCJD,145 with sporadic CJD (sCJD) and 66 patients of Libyan origin but negative family history) from the Israeli registry of CJD conducted since 1954. In all patients AODO in relatives and family trees were documented. Comparison of AODO was done using paired t-test and regression using Pearson correlation for birth and year of onset.

RESULTS:

Initial analysis in 52/73 families in which more than one generation was affected revealed an AODO of 63.30 ± 9.44 in the first generation compared to 56.96 ± 8.99 in the second generation (p < 0.001). However, inspection of individual AODO plotted by year of birth showed a clear rhomboid methodological artifact generated by missing data of many young onset CJD patients who died before the database began to function in 1954 and of many late onset CJD patients missing at the present time since they will only develop the disease in the future. The "generation" effect completely disappears if analysis is performed by year of disease onset or for the periods in which complete data is available.

CONCLUSIONS:

In this very large data set we did not detect true anticipation in fCJD patients. It is plausible that previous reports supporting the presence of anticipation are biased by a rhomboid shaped data availability artifact.

KEYWORDS:

Anticipation; Creutzfeldt-Jakob disease; Prion

PMID:
31814268
DOI:
10.1111/ene.14138

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