Purpose <p>Temporomandibular joint (TMJ) ankylosis impairs jaw function, limiting mouth opening, speech, and mastication, and rendering airway access high-risk. In patients with syndromic conditions such as Pierre Robin Sequence (PRS) and Klippel-Feil Syndrome (KFS), ankylosis presents additional challenges due to airway compromise, restricted mandibular growth, and complex skeletal abnormalities. In addition, predicting the ability to advance the mandible using a prosthesis may be challenging due to anatomic factors.</p> Methods <p>We report the case of an 18-year-old female with TMJ ankylosis, PRS, and KFS, presenting with severe trismus, retrognathia, and failed prior distraction osteogenesis. Imaging confirmed bilateral bony TMJ ankylosis and high-risk airway anatomy due to cervical spine fusion to the skull base. The patient underwent a staged surgical reconstruction involving ankylosis release and delayed alloplastic joint replacement with mandibular advancement. A later revision using new patient-fitted condylar components retained the fossa components and advanced the mandible an additional amount.</p> Results <p>The prosthetic outcome for mandibular advancement remains excellent six years after final reconstruction. There is no evidence of wound dehiscence, prosthesis loosening, or failure, and overall function remains significantly improved.</p> Conclusion <p>This case highlights the complexities of TMJ ankylosis in a patient with multiple craniofacial syndromes and demonstrates the importance of individualized, multidisciplinary planning and the utility of prosthetic TMJ reconstruction. Revision using a new condylar component to further advance the mandible is a potential means of treatment while maintaining the fossa component to minimize variables at the time of surgery.</p>