Nonsyndromic craniosynostosis is more commonly encountered than syndromic cases in pediatric craniofacial surgery. Affected children display characteristic phenotypes according to the suture or sutures involved. Restricted normal growth of the skull can lead to increased intracranial pressure and changes in brain morphology, which in turn may contribute to neurocognitive deficiency. Management has primarily focused on surgical correction of fused sutures prior to 12 months of age to optimize correction of the deformity and to ameliorate the effects of increased intracranial pressure. However, emphasis has recently shifted to better understanding the pathogenesis of neurocognitive impairment observed in these children, along with genetic mutations that contribute to premature suture fusion. Such understanding will provide opportunities for earlier and more specific neurocognitive interventions and for the development of targeted genetic therapy to prevent pathologic suture fusion. The authors review the common types of nonsyndromic craniosynostosis and the epidemiological, genetic, and neurodevelopmental details that are currently known from the literature. In addition, they present the rationale for surgical correction, offer suggestions for timing of intervention, and present some nuances of techniques that they find important in producing consistent results.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, life-threatening bullous genodermatosis (1, 2). Genetic mutations in the COL7A1 gene lead to lack of functional type VII collagen (C7), a large triple-helical protein found beneath the lamina densa (2-4). C7 contains 2 noncollagenous domains (NC1 and NC2) and a central collagenous domain, forming anchoring fibrils (AFs) that are critical to dermal-epidermal basement cohesion (2, 4). Mutations in COL7A1 lead to disruptions in keratinocyte adhesion, reducing mucocu-BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy. METHODS. Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 × 7 cm (35 cm 2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years. RESULTS. No participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019). CONCLUSION. C7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patientreported outcomes. TRIAL REGISTRATION. Clinicaltrials.gov identifier: NCT01263379.

The Furlow Z-plasty yielded excellent speech results in our patient population with minimal and acceptable rates of fistula formation, velopharyngeal insufficiency, and the need for additional corrective surgery.

Therapeutic, III.