Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which was maternally inherited, c.844_851dupCCATGCA, predicting p.Glu284fsX128 and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally inherited. The duplication predicted a frameshift mutation that led to a premature stop codon and premature chain termination, whereas the missense mutation was not functional based on its in vitro expression in mammalian cells. The FFDD skin lesions arise along the sites of fusion of the maxillary and mandibular prominences early in facial development, and Cyp26c1 was expressed exactly along the fusion line for these facial prominences in the first branchial arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and eight Type II or III TWIST2-negative FFDD patients revealed that three of the Type IV patients were homozygous for the duplication, whereas none of the Type II or III patients had CYP26C1 mutations. The seven base pairs duplication was present in 0.3% of healthy controls and 0.3% of patients with other birth defects. These findings suggest that the phenotypic manifestations of FFDD Type IV can be non-penetrant or underascertained. Thus, FFDD Type IV results from the loss of function mutations in CYP26C1.

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.

Ileoscopy with mucosal biopsy is fundamental in the management and surveillance of inflammatory bowel disease patients and intestinal transplant recipients. There is a paucity of data describing the risks of ileoscopy in the presence of a prolapsed stoma. Parastomal hernias are frequently associated with prolapsed stomas. We report the first case of perforation during ileoscopy in the setting of a prolapsed stoma and unrecognized parastomal hernia. Recognition of parastomal hernia associated with stoma prolapse is of paramount importance in patients undergoing ileoscopy as it may increase the risk of perforation.