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Review
. 2020 Aug;28(8):1044-1055.
doi: 10.1038/s41431-020-0582-3. Epub 2020 Feb 18.

Primrose syndrome: a phenotypic comparison of patients with a ZBTB20 missense variant versus a 3q13.31 microdeletion including ZBTB20

Aurélien Juven  1 , Sophie Nambot  1   2   3   4 , Amélie Piton  5 , Nolwenn Jean-Marçais  1   3 , Alice Masurel  1   3 , Patrick Callier  2   3   4 , Nathalie Marle  2 , Anne-Laure Mosca-Boidron  2   4 , Paul Kuentz  2   4 , Christophe Philippe  2   4 , Martin Chevarin  2   4 , Yannis Duffourd  2   4 , Elodie Gautier  1 , Arnold Munnich  6   7 , Marlène Rio  6   7 , Sophie Rondeau  8 , Salima El Chehadeh  9 , Élise Schaefer  9 , Bénédicte Gérard  5 , Sonia Bouquillon  10 , Catherine Vincent Delorme  11 , Christine Francannet  12 , Fanny Laffargue  12 , Laetitia Gouas  13 , Bertrand Isidor  14 , Marie Vincent  14 , Sophie Blesson  15 , Fabienne Giuliano  16 , Olivier Pichon  17 , Cédric Le Caignec  17 , Hubert Journel  18 , Laurence Perrin-Sabourin  19 , Jennifer Fabre-Teste  19 , Dominique Martin  20 , Gaelle Vieville  21 , Klaus Dieterich  22 , Didier Lacombe  23 , Anne-Sophie Denommé-Pichon  1   2   3   4 , Christel Thauvin-Robinet  1   2   3   4 , Laurence Faivre  24   25   26
Affiliations
Review

Primrose syndrome: a phenotypic comparison of patients with a ZBTB20 missense variant versus a 3q13.31 microdeletion including ZBTB20

Aurélien Juven et al. Eur J Hum Genet. 2020 Aug.

Abstract

Primrose syndrome is characterized by variable intellectual deficiency, behavior disorders, facial features with macrocephaly, and a progressive phenotype with hearing loss and ectopic calcifications, distal muscle wasting, and contractures. In 2014, ZBTB20 variants were identified as responsible for this syndrome. Indeed, ZBTB20 plays an important role in cognition, memory, learning processes, and has a transcription repressive effect on numerous genes. A more severe phenotype was discussed in patients with missense single nucleotide variants than in those with large deletions. Here, we report on the clinical and molecular results of 14 patients: 6 carrying ZBTB20 missense SNVs, 1 carrying an early truncating indel, and 7 carrying 3q13.31 deletions, recruited through the AnDDI-Rares network. We compared their phenotypes and reviewed the data of the literature, in order to establish more powerful phenotype-genotype correlations. All 57 patients presented mild-to-severe ID and/or a psychomotor delay. Facial features were similar with macrocephaly, prominent forehead, downslanting palpebral fissures, ptosis, and large ears. Hearing loss was far more frequent in patients with missense SNVs (p = 0.002), ectopic calcification, progressive muscular wasting, and contractures were observed only in patients with missense SNVs (p nonsignificant). Corpus callosum dysgenesis (p = 0.00004), hypothyroidism (p = 0.047), and diabetes were also more frequent in this group. However, the median age was 9.4 years in patients with deletions and truncating variant compared with 15.1 years in those with missense SNVs. Longer follow-up will be necessary to determine whether the phenotype of patients with deletions is also progressive.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Pictures of the patients with ZBTB20 missense variants.
a Patient 1. b Patient 2. c Patient 3. d Patient 5.
Fig. 2
Fig. 2. Pictures of the patients with ZBTB20 microdeletions.
a Patient 7. b Patient 8. c Patient 9. d Patient 11.
Fig. 3
Fig. 3
Position of the ZBTB20 intragenic SNVs and indel of the patients 1–6 and 14.
Fig. 4
Fig. 4
ZBTB20 deletions of patients 7–13 showed in UCSC Genome Browser.
See this image and copyright information in PMC

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Supplementary concepts