Objective:

To report a novel heterozygous nonsense variant in PTHLH associated with brachydactyly type E and short stature in a mother-son pair.

Approach:

• Case Presentation: A 7-year-8-month-old boy and his mother were evaluated for brachydactyly type E and short stature. The boy presented with brachydactyly involving both hands and feet, mild global developmental delay, and subtle craniofacial features. His mother exhibited marked adult short stature and brachydactyly, particularly in the third to fifth digits.

Key Findings:

• The identified PTHLH variant is novel and contributes to the mutational spectrum associated with brachydactyly type E.
• Short stature is common but incompletely penetrant in PTHLH-associated brachydactyly type E.
• Loss-of-function variants, particularly early truncating and frameshift variants, are more frequently associated with growth impairment.

Interpretation:

The findings support the role of PTHLH haploinsufficiency in impaired skeletal growth and highlight the variability in clinical presentation.

Limitations:

• The study is descriptive and relies on previously published data, which may lack uniformity in height reporting.
• Inter- and intrafamilial variability in clinical features complicates the prediction of short stature based on variant type.

Conclusion:

The case illustrates the clinical implications of PTHLH mutations in brachydactyly type E and emphasizes the need for molecular testing in similar presentations.