The aim of this study was to describe directional and fluctuating mandibular asymmetry over time in children with Crouzon or Apert syndrome. Mandibular asymmetry of children between 7.5 and 14 years of age with Crouzon syndrome (n = 35) and Apert syndrome (n = 24) were compared with controls (n = 327). From panoramic radiographs, mandibular directional and fluctuating asymmetry was determined for the three groups. Multilevel statistical techniques were used to describe mandibular asymmetry changes over time. Patients with Crouzon and Apert syndromes showed statistically significant more fluctuating asymmetry for mandibular measures than did controls. Between the Crouzon and Apert syndromes groups, no statistical differences were found in directional and fluctuating asymmetry. The control group showed statistically significantly more directional asymmetry than did patients with Crouzon or Apert syndrome. The controls showed no change over time for the directional asymmetry of condylar-ramal height; however, the directional asymmetry of the gonial angle increased. Patients with Crouzon syndrome showed side dominance for only condylar-ramal height; whereas, patients with Apert syndrome did not show dominance for any of the measurements. Apert and Crouzon syndromes showed developmental instability, in contrast to the controls. No statistically significant longitudinal differences were found for either the directional or the fluctuating asymmetry between Crouzon and Apert syndromes. Findings for fluctuating and directional asymmetry for both syndromes may indicate an inability to cope with genetic and environmental stress during development and treatment, compared with untreated nonsyndromic individuals.