Microdeletion of 17q22q23.2 encompassing TBX2 and TBX4 in a patient with congenital microcephaly, thyroid duct cyst, sensorineural hearing loss, and pulmonary hypertension.

Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation.