Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature

TY - JOUR

T1 - Refining the Primrose syndrome phenotype

T2 - A study of five patients with ZBTB20 de novo variants and a review of the literature

AU - Cleaver, Ruth

AU - Berg, Jonathan

AU - Craft, Emily

AU - Foster, Alison

AU - Gibbons, Richard J.

AU - Hobson, Emma

AU - Lachlan, Katherine

AU - Naik, Swati

AU - Sampson, Julian R.

AU - Sharif, Saba

AU - Smithson, Sarah

AU - Deciphering Developmental Disorders (DDD) Study

AU - Parker, Michael J.

AU - Tatton-Brown, Katrina

N1 - © 2019 Wiley Periodicals, Inc.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype-up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.

AB - Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype-up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.

KW - DDD study

KW - exome sequencing

KW - intellectual disability

KW - Primrose syndrome

KW - ZBTB20

UR - https://www.scopus.com/pages/publications/85059940246

U2 - 10.1002/ajmg.a.61024

DO - 10.1002/ajmg.a.61024

M3 - Article

C2 - 30637921

AN - SCOPUS:85059940246

SN - 1552-4825

VL - 179

SP - 344

EP - 349

JO - American Journal of Medical Genetics Part A

JF - American Journal of Medical Genetics Part A

IS - 3

ER -