In Axenfeld‑Rieger syndrome, how should atlantoaxial instability be screened and managed?

Screening and Management of Atlantoaxial Instability in Axenfeld-Rieger Syndrome

Based on available evidence, perform a one-time screening cervical spine radiograph with flexion-extension views and atlas-dens measurements around age 4 years in children with Axenfeld-Rieger syndrome, following the same protocol recommended for other neurocristopathies with cervical spine anomalies.

Rationale for Screening

Axenfeld-Rieger syndrome (ARS) is a neurocristopathy—a disorder of neural crest cell migration and differentiation 1. The neural crest cells contribute to multiple structures including the anterior eye segment, craniofacial bones, cardiac outflow tract, and importantly, cervical spine structures 2. While the literature on ARS specifically mentions craniofacial and orthopaedic abnormalities requiring surveillance 1, there is no direct evidence establishing the prevalence of atlantoaxial instability in this population.

However, the pathophysiologic similarity to 22q11.2 deletion syndrome (another neurocristopathy) provides the most relevant guidance. In 22q11.2 deletion syndrome, cervical/occipital anomalies are found in almost all children, and a one-time screening for cervical spinal anomalies and instability with radiography including atlas-dens measurements in flexion and extension is recommended around age 4 years 3.

Screening Protocol

Perform the following at approximately 4 years of age:

• Lateral cervical spine radiographs in controlled flexion and extension positions 4
• Measure anterior atlanto-dens interval (AADI) - the distance from the posterior aspect of the anterior arch of C1 to the anterior aspect of the dens
• Measure posterior atlanto-dens interval (PADI) - the space available for the spinal cord
• Assess for os odontoideum (separate ossicle at the dens tip)

Key Radiographic Red Flags

Based on evidence from other syndromic conditions with atlantoaxial instability 5:

• Change in AADI ≥5 mm between flexion and extension
• Change in PADI ≥5 mm between flexion and extension
• Presence of os odontoideum

Clinical Surveillance

Perform annual neurological examinations looking specifically for:

• Hyperreflexia (most significant physical finding predicting need for intervention) 5
• Upper motor neuron signs in lower extremities
• Gait abnormalities
• Bowel or bladder dysfunction
• Neck pain or torticollis
• Muscle weakness or abnormal tone

When to Obtain MRI

Order cervical spine MRI with flexion-extension sequences if any of the following are present:

• Abnormal neurological examination findings
• Radiographic evidence of instability (criteria above)
• Persistent neck symptoms
• Change in neurological status

MRI Red Flags Indicating Surgical Consideration 5:

• Myelomalacia (spinal cord signal changes)
• C1-C2 stenosis ≥80%
• Change in space available for cord (SAC) ≥1.5 mm on flexion-extension

Surgical Indications

Consider posterior cervical fusion (Goel-Harms C1-C2 technique) if ≥4 of the following criteria are present 4, 5:

1. Hyperreflexia on examination
2. Os odontoideum on radiograph
3. AADI change ≥5 mm on flexion-extension
4. PADI change ≥5 mm on flexion-extension
5. Myelomalacia on MRI
6. C1-C2 stenosis ≥80%
7. SAC change ≥1.5 mm on flexion-extension MRI

Patients with 0-1 criteria can typically be managed conservatively with continued surveillance 5. Those with ≥4 criteria have an 80% likelihood of requiring surgical stabilization 5.

Sports Participation

• Unrestricted sports if no atlantoaxial instability is demonstrated 4
• If instability is present but patient is asymptomatic without spinal cord compression, restrict from contact sports and activities with high cervical spine loading
• Any neurological symptoms or documented instability are contraindications to contact sports until surgically stabilized

Important Caveats

The evidence for atlantoaxial instability screening in ARS specifically is extrapolated from other neurocristopathies, particularly 22q11.2 deletion syndrome 3. While cervical anomalies in 22q11.2DS are "rarely consequential" and surgical intervention is uncommon 3, the screening is still recommended given the potential for devastating neurological consequences if instability progresses undetected 4. The same precautionary approach is warranted in ARS given the shared neural crest pathophysiology.