Clinical report: Two patients with atelosteogenesis type I caused by missense mutations affecting the same FLNB residue

We present two patients with Atelosteogenesis Type I (AO type I) caused by two novel Filamin B (FLNB) mutations affecting the same FLNB residue: c.542G>A, predicting p.Gly181Asp and c.542G>C, predicting p.Gly181Arg. Both children had typical manifestations of AO type I, with severe rhizomelic shortening of the extremities, limited elbow and knee extension with mild webbing, pectus excavatum, broad thumbs with brachydactyly that was most marked for digits 3-5, dislocated hips and bilateral talipes equinovarus. Facial features included proptosis, hypertelorism, downslanting palpebral fissures, cleft palate, and retromicrognathia. The clinical course of one child was influenced by airway instability and bronchopulmonary dysplasia that complicated intubation and prevented separation from ventilator support. Respiratory insufficiency with tracheal hypoplasia, laryngeal stenosis, and pulmonary hypoplasia have all been described in patients with AO type I and we conclude that compromised pulmonary function is a major contributor to morbidity and mortality in this condition.