Ectodermal dysplasia

Gene: SMOC2

Green List (high evidence)

Comment on list classification: There are multiple probands reported in literature with biallelic SMOC2 variants and dentin dysplasia, with teeth abnormalities including oligodontia and abnormal tooth shape. Hence, this gene can be promoted to Green at the next update.

Created: 5 Oct 2026, 3:42 p.m. | Last Modified: 5 Oct 2026, 3:42 p.m.

Panel Version: 5.11

PMID: 22152679 Bloch-Zupan et al., 2011
Report of a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. 2 affected children were found to carry a homozygous mutation in SMOC2: c.84+1G>T. Unaffected sibs were heterozygous for the variant. Method: Homozygosity mapping, WES, direct sequencing - SMOC2 was poorly covered on exome.
Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype.

PMID: 23317772 Alfawaz et al., 2013
Consanguineous Pakistani family with oligodontia and microdontia. WES detected a homozygous SMOC2 c.681T>A (p.C227X) mutation in 2 affected individuals.

PMID: 32908163 Morkmued et al., 2020
Same group as PMID: 22152679 Bloch-Zupan et al.
Follow up of a 9yo female patient from the 2011 study. Radiographs showed severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and some skeletal dysplasia features: hyperlordotic curved spinal column, platyspondyly, wider iliac wings.
Mouse model: homozygous smoc2 mutant mice had tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss, supportive of disease association.

SMOC2 is associated with AR Dentin dysplasia, type IA, OMIM:125400 in OMIM (accessed 5th Jun 2026).
Sources: Literature

Created: 5 Oct 2026, 3:38 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dentin dysplasia, type IA, OMIM:125400; atypical dentin dysplasia due to SMOC2 deficiency, MONDO:0017819; dentin dysplasia type 1 with microdontia and shape anomalies

Publications

• 22152679
• 23317772
• 32908163