OBJECTIVE: We describe the 10-year follow-up in a cohort of 16 patients with 
genetically confirmed congenital cataracts, facial dysmorphism, and neuropathy 
(CCFDN) syndrome, providing new insights in the clinical course of the disease.
METHODS: We performed a detailed clinical and paraclinical characterization and 
10-year follow-up study in 16 patients with molecularly defined CCFDN syndrome, 
illustrating that CCFDN is a severe disabling disorder.
RESULTS: All patients initially presented with congenital cataracts along with 
strabismus, facial dysmorphism, short stature, and demyelinating neuropathy. In 
all patients, paresis of small hand muscles and foot extensors worsened with 
disease progression, while ataxia scores remained stable or improved. Nerve 
conduction velocity was normal in early infancy up to 18 months, decreased to 
approximately 20 m/s around age 10 years, and then remained stable; distal motor 
latency was prolonged. Sensory nerve conduction velocities were slowed, and 
initially of normal amplitude. With disease progression, both sensory and motor 
nerves showed reduction of amplitudes indicating axonal loss. In 6 patients, 
acute severe proximal weakness and myalgia after febrile infections, along with 
rhabdomyolysis, myoglobinuria, and hyperCKemia, led to a less favorable outcome 
and permanent loss of ambulation in 3 patients.
CONCLUSIONS: CCFDN should be classified as a recessive demyelinating 
sensory-motor neuropathy, and axonal loss is a major determinant of long-term 
outcomes and disability. Patients benefit from early and ongoing physiotherapy, 
and should be thoroughly counseled regarding virus-triggered rhabdomyolysis and 
the risk of malignant hyperthermia. Whether supplementation with liposoluble 
vitamins results in a therapeutic benefit should be evaluated in further 
studies.