Parental Perception of Quality of Life and Impact of Short Stature in Children with Hypochondroplasia and Other Genetic Causes of Short Stature.

Introduction: Short stature can lead to physical limitations and socioemotional effects limiting a child and parents' quality of life (QoL). This study investigates the impact of hypochondroplasia and other genetic causes (ACAN, NPR2 mutations, and RASopathy) of short stature on QoL.

Methods: Parents of participants in an ongoing phase II clinical trial of vosoritide in children with selected genetic causes of short stature completed the Quality of Life in Short Stature Youth (QoLISSY) survey. Results from the survey domains (Total, Physical, Social, Emotional, Coping, Beliefs, Future, and Effects on parents) were compared to a reference population with idiopathic short stature (ISS) and growth hormone deficiency (GHD).

Results: The cohort had lower mean total QoL scores compared to the reference population (54.0+/- 19.7 vs. 70.0+/- 22.0, p value <0.001), along with lower Physical (44.8+/- 21.2 vs. 71.8+/-23.2, p value <0.001) and Social scores (54.0+/-22.2 vs. 69.4+/-25.2, p value <0.001), and worse Effects on parents (52.3+/- 20.0 vs. 65.68 +/- 24.5, p value <0.0001). Older age and lower baseline height were associated with lower scores. Lower QoL scores were more prominent in males compared to the reference. When comparing genetic diagnoses, patients with NPR2 mutations had the lowest QoL scores.

Conclusion: Patients with hypochondroplasia and other genetic causes of short stature had lower scores in multiple domains of QoL compared to ISS/GHD. Older age, male sex, and shorter stature may exacerbate effects on QoL. Additional studies to further explore these associations can clarify the unique challenges and facilitate appropriate medical and psychosocial support for children and their families.