Vertebral Anomalies And Variable Endocrine And T-Cell Dysfunction

A number sign (#) is used with this entry because of evidence that vertebral anomalies and variable endocrine and T-cell dysfunction (VETD) is caused by heterozygous mutation in the TBX2 gene (600747) on chromosome 17q23.

Description

Vertebral anomalies and variable endocrine and T-cell dysfunction is a syndrome characterized by an overlapping spectrum of features. Skeletal malformations primarily involve the vertebrae, and endocrine abnormalities involving parathyroid hormone (PTH; 168450), growth hormone (GH1; 139250), and the thyroid gland have been reported. T-cell abnormalities have been observed, with some patients showing thymus gland aplasia or hypoplasia. Patients have mild craniofacial dysmorphism, and some show developmental delay or behavioral problems. Cardiac defects may be present (Liu et al., 2018).

Clinical Features

Liu et al. (2018) reported 4 affected individuals from 2 unrelated families with congenital cardiac defects, skeletal abnormalities, facial dysmorphisms, variable developmental delay, and endocrine system disorders. In the first family, a mother, son, and daughter were affected. The son and daughter had thymus aplasia or hypoplasia, with absent or low T cell numbers, whereas their mother had low naive T cells. All 3 exhibited hypertelorism, epicanthal folds, ear deformities, cleft palate, Sprengel deformity, Klippel-Feil anomaly, and camptodactyly of the third and fourth fingers. The son also had atrial septal defect and the daughter had patent ductus arteriosus, both reported as closed at the time of assessment. Endocrine anomalies in this family included autoimmune hypothyroidism in the son, hypoparathyroidism in the daughter, and low-normal PTH in the mother. The son showed average intelligence with attention-deficit/hyperactivity disorder and autistic behaviors, whereas the daughter showed mild developmental delay; their mother had normal intelligence. The authors also studied an unrelated boy with short stature due to growth hormone deficiency, high-arched narrow palate, double-outlet right ventricle and pulmonary stenosis, congenital fusions of the thoracic spine and hemivertebrae, mild facial dysmorphism, and developmental delay. He had no immune-related symptoms, but did not undergo immune function testing.

Molecular Genetics

By whole-genome sequencing in a family with vertebral anomalies and variable endocrine and T-cell dysfunction, Liu et al. (2018) identified heterozygosity for a missense mutation in the TBX2 gene (R20Q; 600747.0001) in the affected mother and 2 children, but not in the unaffected father. In an unrelated boy with VETD, they identified heterozygosity for a de novo missense mutation in TBX2 (R305H; 600747.0002).