Cleft palate morphology, genetic etiology, and risk of mortality in infants with Robin sequence

• Published in: American journal of medical genetics. Part A Vol. 185; no. 12; pp. 3694 - 3700
• Main Authors: Wenger, Tara L., Perkins, Jonathan, Parish‐Morris, Julia, Hing, Anne V., Chen, Maida L., Cielo, Christopher M., Li, Dong, Bhoj, Elizabeth J., Hakonarson, Hakon, Zackai, Elaine, McDonald‐McGinn, Donna M., Taylor, Jesse A., Jackson, Oksana, Sie, Kathleen, Bly, Randall, Dahl, John, Evans, Kelly N.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2021; Wiley Subscription Services, Inc
• Subjects: Arthritis - diagnostic imaging; Arthritis - genetics; Arthritis - mortality; Arthritis - pathology; Birth defects; Child; Child, Preschool; Children; Cleft Lip - diagnostic imaging; Cleft Lip - genetics; Cleft Lip - mortality; Cleft Lip - pathology; Cleft lip/palate; cleft palate; Cleft Palate - diagnostic imaging; Cleft Palate - genetics; Cleft Palate - mortality; Cleft Palate - pathology; Connective Tissue Diseases - diagnostic imaging; Connective Tissue Diseases - genetics; Connective Tissue Diseases - mortality; Connective Tissue Diseases - pathology; Etiology; Female; Hearing Loss, Sensorineural - diagnostic imaging; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - mortality; Hearing Loss, Sensorineural - pathology; Humans; Infant; Male; Morphology; Mortality; Patients; Pierre Robin Syndrome - diagnostic imaging; Pierre Robin Syndrome - genetics; Pierre Robin Syndrome - mortality; Pierre Robin Syndrome - pathology; Retinal Detachment - diagnostic imaging; Retinal Detachment - genetics; Retinal Detachment - mortality; Retinal Detachment - pathology; Retrospective Studies; Robin sequence; Stickler syndrome; mortality; cleft palate; Robin sequence; Stickler syndrome
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62430

Robin sequence (RS) has many genetic and nongenetic causes, including isolated Robin sequence (iRS), Stickler syndrome (SS), and other syndromes (SyndRS). The purpose of this study was to determine if the presence and type of cleft palate varies between etiologic groups. A secondary endpoint was to determine the relationship of etiologic group, cleft type, and mortality. Retrospective chart review of patients with RS at two high‐volume craniofacial centers. 295 patients with RS identified. CP was identified in 97% with iRS, 95% with SS, and 70% of those with SyndRS (p < .0001). U‐shaped CP was seen in 86% of iRS, 82% with SS, but only 27% with SyndRS (p < .0001). At one institution, 12 children (6%) with RS died, all from the SyndRS group (p < .0001). All died due to medical comorbidities related to their syndrome. Only 25% of children who died had a U‐shaped CP. The most common palatal morphology among those who died was an intact palate. U‐shaped CP was most strongly associated with iRS and SS, and with a lower risk of mortality. RS with submucous CP, cleft lip and palate or intact palate was strongly suggestive of an underlying genetic syndrome and higher risk of mortality.