Neuroferritinopathy

Clinical characteristics: Neuroferritinopathy is an adult-onset progressive movement disorder characterized by chorea or dystonia and speech and swallowing deficits. The movement disorder typically affects one or two limbs and progresses to become more generalized within 20 years of disease onset. When present, asymmetry in the movement abnormalities remains throughout the course of the disorder. Most individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time.

Diagnosis/testing: The diagnosis of neuroferritinopathy is established in a proband with typical clinical findings and/or identification of a heterozygous pathogenic variant in FTL by molecular testing.

Management: Treatment of manifestations: While the movement disorder is particularly resistant to conventional therapy, some response has been recorded with levodopa, tetrabenazine, orphenadrine, benzhexol, sulpiride, diazepam, clonazepam, and deanol in standard doses. Botulinum toxin may be helpful for painful focal dystonia. Physical therapy is recommended to maintain mobility and prevent contractures.

Agents/circumstances to avoid: Iron supplements.

Genetic counseling: Neuroferritinopathy is inherited in an autosomal dominant manner with 100% penetrance. Most individuals diagnosed with neuroferritinopathy have an affected parent; the proportion of individuals with neuroferritinopathy caused by a de novo pathogenic variant is unknown but likely rare. Each child of an individual with neuroferritinopathy has a 50% chance of inheriting the pathogenic variant. Prenatal and preimplantation genetic testing are possible if the FTL pathogenic variant in the family is known.