Pantothenate Kinase-Associated Neurodegeneration

Clinical characteristics: Pantothenate kinase-associated neurodegeneration (PKAN) is a type of neurodegeneration with brain iron accumulation (NBIA). The phenotypic spectrum of PKAN includes classic PKAN and atypical PKAN. Classic PKAN is characterized by early-childhood onset of progressive dystonia, dysarthria, rigidity, and choreoathetosis. Pigmentary retinal degeneration is common. Atypical PKAN is characterized by later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease.

Diagnosis/testing: The diagnosis of PKAN is established in a proband with the characteristic clinical features and the "eye of the tiger" sign identified on brain MRI (a central region of hyperintensity surrounded by a rim of hypointensity on coronal or transverse T₂-weighted images of the globus pallidus). Identification of biallelic PANK2 pathogenic variants on molecular genetic testing confirms the diagnosis.

Management: Treatment of manifestations: Intramuscular botulinum toxin, ablative pallidotomy or thalmotomy, intrathecal or oral baclofen, oral trihexyphenidyl, deep brain stimulation, physical therapy and occupational therapy to maintain joint mobility, referral for adaptive aids (walker, wheelchair) for gait abnormalities, speech therapy and/or assistive communication devices, treatment for retinopathy by ophthalmology, referral to community resources: financial services, services for the blind, and educational programs.

Prevention of secondary complications: Full-mouth dental extraction when severe orobuccolingual dystonia results in recurrent tongue biting; gastrostomy tube feeding as needed.

Surveillance: Evaluation for treatable causes of pain during episodes of extreme distress; monitoring of height and weight; routine ophthalmologic assessment; oral assessment for trauma, assessment of ambulation and speech abilities, feeding and nutrition assessment.

Genetic counseling: PKAN is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for a pregnancy at risk, and preimplantation genetic testing are possible if both pathogenic variants have been identified in an affected family member.