Mutations in CRTAP lead to an extremely rare form of recessive osteogenesis imperfecta (OI). CRTAP deficient mice have a brachycephalic skull, fusion of facial bones, midface retrusion and class III dental malocclusion, but in humans, the craniofacial and dental phenotype has not been reported in detail. Here, we describe craniofacial and dental findings in two 11-year-old girls with biallelic CRTAP mutations.

Patient 1 has a homozygous c.472-1021C>G variant in CRTAP intron 1 and a moderately severe OI phenotype. The variant is known to create a cryptic splice site, leading to a frameshift and nonsense-mediated RNA decay. Patient 1 started intravenous bisphosphonate treatment at 2 years of age. At age 11 years, height Z-score was +0.6. She had a short and wide face, concave profile and class III malocclusion, with a prognathic mandible and an antero-posterior crossbite. A panoramic radiograph showed a poor angulation of the second upper right premolar, and no dentinogenesis imperfecta or dental agenesis. Cone-beam computed tomography confirmed these findings and did not reveal any other abnormalities.

Patient 2 has a homozygous CRTAP deletion of two amino acids (c.804_809del, p.Glu269_Val270del) and a severe OI phenotype. As previously established, the variant leads to instability of CRTAP protein. Intravenous bisphosphonate treatment was started at the age of 15 months. At 11 years of age her height Z-score was −9.7. She had a long and narrow face and convex profile, maxillary retrusion leading to a class III malocclusion, an edge-to-edge overjet and lateral open bite. Panoramic radiographs showed no dental abnormalities. Cone-beam computed tomography showed occipital bossing, platybasia and wormian bones.

In these two girls with CRTAP mutations, the severity of the skeletal phenotype was mirrored in the severity of the craniofacial phenotype. Class III malocclusion and antero-posterior crossbite were a common trait, while dental agenesis or dentinogenesis imperfecta were not detected.