Concurrent mutations in <i>DNAH5</i> and <i>FOXE3</i> genes: a unique occurrence in infancy

A 3-month-old female infant from South India presented with microphthalmia and features suggestive of primary ciliary dyskinesia (PCD). She was born to a third-degree consanguineous couple and showed signs of breathing difficulty at birth, frequent respiratory infections, bilateral microphthalmia, hypertelorism, a flat nasal bridge, rounded lips, crackles in the lungs, and situs inversus. Whole exome sequencing revealed homozygous pathogenic mutations in two genes: a frameshift mutation in Dynein Axonemal Heavy Chain 5 (<i>DNAH5</i>), linked to PCD, and a null mutation in Forkhead Box E3 (<i>FOXE3</i>), associated with eye developmental disorders such as microphthalmia and primary aphakia. <i>FOXE3</i> encodes a forkhead transcription factor critical for lens development, while <i>DNAH5</i> is essential for the function of motile cilia. Both variants were classified as pathogenic per American College of Medical Genetics and Genomics guidelines. The recurrence risk was estimated at 25% in future pregnancies and genetic counselling was provided.