Two siblings with Chudley-McCullough Syndrome were born to healthy consanguineous parents of Libyan descent. They presented with hydrocephalus identified during the neonatal period and bilateral profound hearing loss by one year of age. Genetic testing identified a homozygous, novel GPSM2 nonsense variant, c.1420C>T ( p.474Arg*).  We review findings from the literature on patient's with Chudley-McCullough Syndrome, their genetic mutations, and provide suggestions for screening young children presenting with severe-profound sensorineural hearing loss with structural brain abnormalities.