Consideration of the thoracic phenotype of cerebro‐costo‐mandibular syndrome

Abstract

Cerebro‐costo‐mandibular syndrome (CCMS) is a congenital condition with skeletal and orofacial abnormalities that often results in respiratory distress in neonates. The three main phenotypes in the thorax are posterior rib gaps, abnormal costovertebral articulation and absent ribs. Although the condition can be lethal, accurate diagnosis, and subsequent management help improve the survival rate. Mutations in the causative gene SNRPB have been identified, however, the mechanism whereby the skeletal phenotypes affect respiratory function is not well‐studied due to the multiple skeletal phenotypes, lack of anatomy‐based studies into the condition and rarity of CCMS cases. This review aims to clarify the extent to which the three main skeletal phenotypes in the thorax contribute to respiratory distress in neonates with CCMS. Despite the posterior rib gaps being unique to this condition and visually striking on radiographic images, anatomical consideration, and meta‐analyses suggested that they might not be the significant factor in causing respiratory distress in neonates. Rather, the increase in chest wall compliance due to the rib gaps and the decrease in compliance at the costovertebral complex was considered to result in an equilibrium, minimizing the impact of these abnormalities. The absence of floating ribs is likely insignificant as seen in the general population; however, a further absence of ribs or vestigial rib formation is associated with respiratory distress and increased lethality. Based on these, we propose to evaluate the number of absent or vestigial ribs as a priority indicator to develop a personalized treatment plan based on the phenotypes exhibited.

Defects of the spliceosomal gene SNRPB affect osteo‐ and chondro‐differentiation

“…Cerebro-costo-mandibular syndrome (CCMS) is a congenital skeletal dysmorphism comprising micrognathia, cleft palate, glossoptosis, rib gaps, scoliosis, a narrow chest and subsequent upper airway obstruction [1][2][3]. The genetic origin of CCMS was identified as mutations within the SNRPB gene, encoding Small Nuclear Ribonucleoprotein Polypeptides B and B 0 (SmB/B 0 ), which lead to reduced expression levels of functional SmB/B 0 proteins [4,5].…”