The clinical spectrum and diagnosis of Rubenstein-Taybi syndrome

Abstract

Genomic medicine has enabled molecular diagnosis for a variety of conditions, however the question of who and when to sequence continues to evolve. In this volume of The Journal, Levetan et al. report an international cross-sectional analysis from 311 individual with a diagnosis of Rubenstein-Taybi syndrome (RSTS), a rare genetic disorder typically characterized by short stature, broad thumbs, and distinctive facial features. As the features of RSTS may not be obvious during the neonatal period, the authors investigated when and how a diagnosis was made and assessed associated systemic involvement in the newborn period. Their analysis revealed several important features. First, prenatal ultrasound findings were present in 94 (30%) cases, including non-specific findings such as polyhydramnios and growth restriction, yet only two participants received prenatal molecular diagnoses. This portends the potential utility of a comprehensive prenatal screen for genetic conditions, the results of which could modulate pregnancy and postnatal care. Second, in 59 (22.1%) of cases, concerns were first noted by parents, not healthcare providers. This highlights the importance of a family-centered approach and basic familiarity with the spectrum of rare disorders that can present in the neonatal period. Third, the study revealed that most RSTS in this cohort was diagnosed in the first month of life (85.9%), even though <1% of cases were diagnosed prenatally. This manuscript exemplifies how data aggregation in rare disorders elucidates the spectrum of clinical presentations and provides evidence for the utility of comprehensive genetic assessment, especially in the prenatal period. Article page 106 ▸ Rubinstein-Taybi Syndrome: Presentation in the First Month of LifeThe Journal of PediatricsVol. 249PreviewThis web-based survey of 311 respondents from 25 countries provides additional information about the early presentation of Rubinstein–Taybi syndrome. Most (86%) infants present during the neonatal period, with 69% of these within 24 hours of life. Prolonged hospital stay is common (61%). Full-Text PDF