Introduction: During a two-stage free gracilis muscle transfer (FGMT) to restore smile to patients with facial paralysis, some surgeons assess nerve regeneration through the cross-face nerve graft (CFNG) with the Tinel sign and a nerve biopsy. Objective: To test whether ultimate smile reanimation outcomes are correlated with (1) the Tinel sign or (2) myelinated axons of the biopsied CFNG at the time of FGMT. Methods: Retrospective case series was performed at a tertiary care facial nerve center. Dynamic smile outcomes were quantified with Emotrics analysis of pre- and postoperative photographs. Results: Of the 113 FGMT surgeries by CFNG performed since 2002, 92 patients had pre- and postoperative photo-documentation. Most patients (89%, N = 82) had a positive Tinel sign at the time of FGMT; however, 14 patients with positive Tinel signs were deemed failures. Interestingly, 4 patients with a negative Tinel sign went on to have successful dynamic outcomes and 16 patients lacking myelinated axons in their CFNG biopsy ultimately achieved successful smile outcomes. Conclusion: Although the majority of patients had a positive Tinel sign and myelinated axons in the CFNG at the time of FGMT, the presence or absence of either factor did not predict ultimate smile outcome in this series.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.