Clinical and genetic characterization of patients with Pierre Robin sequence and spinal disease: review of the literature and novel terminal 10q deletion

Abstract

Introduction The Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS. Methods We explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion. Results Our systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical detethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS. Conclusion Spinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management.

Craniofacial disorders and dysplasias: Molecular, clinical, and management perspectives

“…Pierre Robin sequence (PRS; OMIM 311895 ) is a genetic birth defect manifesting clinically as micrognathia, glossoptosis and airway obstruction that may include cleft palate and feeding difficulties ( Yekula et al, 2020 ; Zhang et al, 2019 ). About half of PRS cases are isolated, while the others are syndromic ( Yekula et al, 2020 ). PRS is a sequence of disorders, with one abnormality resulting in the next.…”

“…PRS is initiated with mandibular hypoplasia, causing posterior positioning of the tongue (glossoptosis) and increased potential for respiratory compromise. Furthermore, trapping of the base of the tongue in the nasopharynx consequently impedes palate formation, leading to palatal cleft ( Hsieh and Woo, 2019 ; Yekula et al, 2020 ). Mechanical, neurological maturation and mandibular compression have all been postulated as causes of the hypoplastic mandible ( Giudice et al, 2018 ).…”