Skeletal dysplasia

Gene: ZBTB20

Red List (low evidence)

Comment on list classification: As skeletal dysplasia is a relatively rare feature in Primrose syndrome patients (5 of more than 50 cases reported to have skeletal dysplasia), this gene should remain Red on this panel. R27 Paediatric disorders is a more suitable Clinical Indication for this multisystemic disorder.

Created: 7 Jul 2026, 2:07 p.m. | Last Modified: 7 Jul 2026, 2:09 p.m.

Panel Version: 9.26

PMID: 31321892 Ferreira et al., 2019
P1 - male proband of European ancestry with Primrose syndrome: macrocephaly, hypoplasia of CC, mild kyphosis and multiple wormian bones, GDD. Trio WES detected a de novo ZBTB20 c.1822T>C, p.Cys608Arg variant.
P2 - male patient, Brazilian, with Primrose syndrome: GDD, strabismus, distal muscle wasting, ASD, hearing impairment, brain and ear calcifications seen on CT & MRI, dysmorphic features. Targeted ZBTB20 seq detected a c.1873A>G, p.Met625Val variant - not detected in the mother of siblings, father's DNA unavailable. No skeletal abnormalities apart from lumbar hyperlordosis.

PMID: 32473227 Arora et al., 2020
Report of 5 probands (all male, aged 2-23 yrs at time of report) with Primrose syndrome, one each from India, Japan, Europe, Lebanon and Africa. 4 families were noted to be non-consanguineous and 1 unspecified.
All 5 patients carried de novo heterozygous missense variants in ZBTB20: p.Thr627Ala, p.Cys639Tyr, p.His600Gln, p.Leu621Phe, & p.Cys639Tyr.
Phenotypic spectrum: learning disability (5/5), facial dysmorphism (5/5), macrocephaly (4/5), hearing loss (3/5), corpus callosum abnormality on MRI (2/5). In addition, all 5 probands had skeletal features: Wormian bones (5/5), Epiphyseal abnormalities (5/5), notably slender bones (5/5), spine involvement (3/5).

https://www.ncbi.nlm.nih.gov/books/NBK570205/ - Primrose syndrome GeneReviews entry mentions 52 reported individuals. Skeletal abnormalities are not noted to be the main characteristic features. Some patients present with scoliosis and skull specific abormalities e.g., wormian bones, without wider skeletal involvement. The primary features consistent in most cases are: intellectual disability (100%), hearing loss (83%), dysmorphic facial features (>70%), hypotonia (76%), and autism (70%), with many other less specific features.

ZBTB20 is associated with AD Primrose syndrome, OMIM:259050 (OMIM accessed 7th July 2026).

Sources: Literature

Created: 7 Jul 2026, 1:56 p.m. | Last Modified: 7 Jul 2026, 2:04 p.m.

Panel Version: 9.23

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Primrose syndrome, OMIM:259050; Primrose syndrome, MONDO:0009798; intellectual disability-cataracts-calcified pinnae-myopathy syndrome

Publications

• 31321892
• 32473227