Skeletal dysplasia

Gene: TBX2

Green List (high evidence)

Comment on list classification: There are now 4 unrelated individuals reported with heterozygous TBX2 variants and skeletal malformations - a proband with severe chondrodysplasia punctata, a family with dominant osteochondrodysplasia, a patient with congenital fusions of the thoracic spine and hemivertebrae with scoliosis, and another individual rib fusions and scoliosis. Hence, this gene can now be promoted to Green on Skeletal dysplasia.

Created: 13 May 2026, 3:27 p.m. | Last Modified: 13 May 2026, 3:27 p.m.

Panel Version: 9.9

PMID: 36733940 Rafeeq et al., 2023
Patient (5yo female from Pakistan) with severe chondrodysplasia punctata with developmental delay, deceased at 5yrs. WES detected a de novo heterozygous c.529A>T; p.Lys177* variant in TBX2. MRI and radiographs showed platybasia at the skull base, delayed myelination for the patient’s age, and severe skeletal deformities. No hearing loss.

PMID: 35311234 Makitie et al., 2022
Report of a three-generation Finnish family with an unusual, autosomal dominant form of osteochondrodysplasia and an empty sella. Affected individuals (age range 24-44 years) exhibit codfish-shaped vertebrae, severe early-onset and debilitating osteoarthritis and an empty sella without endocrine abnormalities. Joint pain, obesity, and dysmorphic features were also noted. WES detected heterozygous c.899C>T (p.Thr300Met) variant in TBX2. Proband's father, and grandfather were similarly affected, deceased in their 40s - only proband and unaffected family members were sequenced. Clinical diagnosis of osteochondrodysplasia and osteoarthritis. No hearing loss or impaired cognition.

PMID: 29726930 Liu et al., 2018
Four individuals with an overlapping spectrum of craniofacial dysmorphisms, cardiac anomalies (PDA, double outlet right ventricle), skeletal malformations, immune deficiency, endocrine abnormalities and developmental impairments, reminiscent of DiGeorge syndrome. All 4 are heterozygotes for TBX2 variants: p.R20Q variant is shared by three affected family members - segregated in autosomal dominant manner; the fourth unrelated individual has a de novo p.R305H mutation. Skeletal features: congenital fusions of the thoracic spine and hemivertebrae with scoliosis (P4), rib fusions, scoliosis (P1), campodactyly (P1-3).
Sources: Literature

Created: 13 May 2026, 3:19 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Vertebral anomalies and variable endocrine and T-cell dysfunction, OMIM:618223; vertebral anomalies and variable endocrine and T-cell dysfunction, MONDO:0032607; chondrodysplasia, MONDO:0022723

Publications

• 29726930
• 35311234
• 36733940