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Primrose syndrome: Characterization of the phenotype in 42 patients
Author(s) -
Melis Daniela,
Carvalho Daniel,
BarbaroDieber Tina,
Espay Alberto J.,
Gambello Michael J.,
Gener Blanca,
Gerkes Erica,
Hitzert Marrit M.,
Hove Hanne B.,
Jansen Sandra,
Jira Petr E.,
Lachlan Katherine,
Menke Leonie A.,
Narayanan Vinodh,
Ortiz Damara,
Overwater Eline,
Posmyk Renata,
Ramsey Keri,
Rossi Alessandro,
Sandoval Renata Lazari,
Stumpel Constance,
Stuurman Kyra E.,
Cordeddu Viviana,
Turnpenny Peter,
Strisciuglio Pietro,
Tartaglia Marco,
Unger Sheela,
Waters Todd,
Turnbull Clare,
Hennekam Raoul C.
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13749
Subject(s) - macrocephaly , camptodactyly , medicine , wasting , missense mutation , phenotype , pathology , endocrinology , pediatrics , physiology , genetics , anatomy , biology , gene
Abstract Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down‐slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20 . Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha‐fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype‐phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.