Epigenetics and Surgical Timing Inform Safety and Outcomes of Tongue Reduction for Patients with Beckwith-Wiedemann Syndrome
Year: 2023
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Macroglossia is a cardinal feature of Beckwith-Wiedemann syndrome (BWS). Optimal timing of tongue reduction is debated due to the spectrum of phenotypic severity across and within epigenetic subtypes. Operative timing is of critical importance due to its impacts on obstructive sleep apnea, speech progression, craniofacial growth, and dental development. This study leverages a large cohort of molecularly characterized patients with BWS to correlate epigenetic diagnosis with phenotype and treatment outcome. METHODS: Patients with BWS seen in consultation for macroglossia from 2009-2022 were reviewed for phenotype, molecular diagnosis, tongue reduction status, timing of surgery (early = under 12 months, late = after 12 months), length of hospital stay, perioperative complications, and repeated tongue reductions. The surgical technique used at our institution is an anterior resection with a modified-W shaped pattern. The frequency of tongue reduction was compared across epigenetic subtypes. Phenotypic features including hemihypertrophy, omphalocele, hyperinsulinism, embryonal tumors, macrosomia at birth, facial nevus flammeus, ear creases/pits, organomegaly, and umbilical hernia/diastasis were compared across patients who did and did not undergo tongue reduction. Complications were compared between patients undergoing early and late tongue reduction. RESULTS: Two hundred thirty-seven patients were included, 95 (40%) of whom underwent tongue reduction (47 early, 48 late). Imprinting control region 2 loss of methylation (IC2 LOM) was the most common epigenotype (61%). Paternal uniparental isodisomy for chromosome 11 (pUPD11) comprised a larger proportion of patients undergoing tongue reduction (18%) than those not undergoing surgery (8%, p=0.024) and was associated with need for repeat surgery (OR 4.49, 95% CI 1.06-18.98, p=0.041). Certain phenotypic features including omphalocele (OR 4.20, 95% CI 2.11-8.35, p<0.001), hyperinsulinism (OR 4.39, 95% CI 2.14-9.03, p<0.001), and organomegaly (OR 3.68, 95% CI 1.98-6.86, p<0.001) were more frequently observed in patients undergoing tongue reduction. Length of hospitalization among patients admitted for early tongue reduction was 9.5 days (IQR 6.8-12.5) compared to 3.0 days (IQR 2.0-5.0) in the late surgery cohort (p<0.001). Duration of postoperative intubation was significantly longer in the early surgery group (5.0 days, IQR 2.8-7.0) compared to the late surgery group (0 days, IQR 0.0-1.0, p<0.001). Complications including wound dehiscence, ventilator associated pneumonia, and unplanned extubation were more common in patients undergoing early surgery (20%) than late surgery (4%, OR 5.70, 95% CI 1.14-28.55, p=0.034). CONCLUSIONS: The results support correlations between severity of features such as omphalocele, hyperinsulinism, and organomegaly and severe macroglossia necessitating tongue reduction. Certain genetic subtypes, namely pUPD11, are associated with more frequent tongue reduction and repeated surgery, perhaps due to tongue regrowth. While early operation is indicated for relief of obstructive sleep apnea, this must be weighed against longer hospitalization and intubation as well as increased risk of perioperative complications, most of which are non-surgical. This study highlights how molecular diagnosis advances clinical care in BWS by risk stratifying clinical outcomes in a multidisciplinary care center.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,195
OpenAlex ID: W4387739007