Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

Complex pediatric orbital fractures combined with traumatic brain injury: treatment and follow-up.

The treatment of orbital fractures aims at the restoration of orbital anatomy and prevention of posttraumatic sequels. The treatment of facial fractures in patients with traumatic brain injury may necessitate a postponement of fracture surgery to allow for brain recovery. However, such delay of reconstruction in complex orbital fractures may lead to inferior results. Fourteen pediatric patients with complex orbital fractures were retrospectively reviewed. Eleven patients (79%) had brain injury, with a mean Glasgow Coma Scale score of 8.6 at initial evaluation. Fracture patterns were highly complex with many bilateral and multiple orbital wall fractures. Six patients (43%) had injuries to the medial canthal tendon, as part of a naso-orbito-ethmoid fracture. Mean follow-up time was 4.7 years (range, 1.2-13.1 years). Eleven patients (79%) had reconstructive surgery early (within 3 weeks), and 3 (29%) patients had the surgery postponed. Four patients had secondary surgeries for enophthalmos and medial canthal dislocation. Eighty-two percent of patients with brain injury had a good overall neurologic outcome (Glasgow Outcome Scale score of 1 or 2). Sixty-seven percent of patients had a good aesthetic outcome without any need for revisional surgery. Medial canthal injury and late surgery both correlated with an inferior aesthetic result. In conclusion, good results with respect to mental outcome and aesthetics can be achieved in highly complex orbital fractures combined with brain injury. Delayed surgery and medial canthal tendon injury predispose for posttraumatic sequels and secondary surgery.