Cranial Nerve Diseases study with SNP/CNV Genotypes (NGS), WGS data on KFDRC (899 participants)

phs001247 — GMKF: Kids First Pediatric Research Program on Congenital Cranial    Dysinnervation Disorders and Related Birth Defects

The Gabriella Miller Kids First Pediatric Research Program (<a href="https://www.commonfund.nih.gov/KidsFirst">Gabriella Miller Kids First Pediatric Research Program</a>) (Kids First) is a trans-NIH effort initiated in response to the <a href="https://www.govtrack.us/congress/bills/113/hr2019">2014 Gabriella Miller Kids First Research Act</a> and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). Both, childhood cancers and structural birth defects are critical and costly conditions associated with substantial morbidity and mortality. Elucidating the underlying genetic etiology of these diseases has the potential to profoundly improve preventative measures, diagnostics, and therapeutic interventions. Whole Genome Sequence (WGS) and phenotypic data from this study are accessible through dbGaP and <a href="https://kidsfirstdrc.org">kidsfirstdrc.org</a>, where other Kids First datasets can also be accessed. Goals of this ongoing study are to identify novel "congenital cranial dysinnervation disorder" (CCDD) genes and define the role of the wildtype and mutant genes in normal and aberrant development. The umbrella term (CCDD) refers to congenital birth defects with malformation of one or more cranial nerves, typically resulting in limitations of eye and/or face movement. Examples of CCDDs include congenital fibrosis of the extraocular muscles (CFEOM), congenital ptosis, Duane retraction syndrome (DRS), horizontal gaze palsy with progressive scoliosis (HGPPS), congenital 3rd, 4th or 6th nerve palsies, Moebius syndrome (MBS), and hereditary congenital facial paresis (HCFP). In some cases, anosmia, and disorders of hearing, sucking, chewing, swallowing, and breathing may also be classified as CCDDs. CCDDs can be accompanied by additional birth defects such as intellectual and social disabilities, developmental delays, limb anomalies, and cardiac, GI, and GU disorders. The genetic basis of multiple CCDDs has been determined, and the gene mutations typically alter cranial motor neuron identity or function, or perturb axon growth and guidance. Despite these successes, the genetic etiologies of many inherited CCDDs remain unidentified.