Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome).
OBJECTIVE
The onset of pantothenate kinase-associated neurodegeneration (PKAN) occurs in the first and second decade of life and a pigmentary retinal degeneration is a feature of the disorder. Since the neuro-ophthalmologic and electroretinographic (ERG) features have never been well delineated, we describe them in 16 patients with PKAN.


METHODS
Observational case series.


METHODS
Sixteen patients with genetic and neuroimaging-confirmed PKAN were examined. Ten underwent neuro-ophthalmologic examination and all had ERGs.


RESULTS
Of the 10 who underwent neuro-ophthalmologic examination, all showed saccadic pursuits and eight showed hypometric or slowed vertical saccades. Seven of eight had inability to suppress the vestibulo-ocular reflex; two patients could not cooperate. Two had square wave jerks and four had poor convergence. Vertical optokinetic responses were abnormal in five, and two patients had blepharospasm. Eight patients had sectoral iris paralysis and partial loss of the pupillary ruff consistent with Adie's pupils in both eyes. Only four of 10 examined patients showed a pigmentary retinopathy, but 11 of 16 had abnormal ERGs ranging from mild cone abnormalities to severe rod-cone dysfunction. No patient had optic atrophy. The PANK2 mutations of all of the patients were heterogeneous.


CONCLUSIONS
Adie's-like pupils, abnormal vertical saccades, and saccadic pursuits were very common. These findings suggest that mid-brain degeneration occurs in PKAN more frequently than previously thought. ERG abnormalities were present in approximately 70% and no patient had optic atrophy. Although genotype-ocular phenotype correlations could not be established, allelic differences probably contributed to the variable clinical expression of retinopathy and other clinical characteristics in these patients.
Egan
Robert A
RA
Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland 97201, USA. eganr@ohsu.edu
Weleber
Richard G
RG
Hogarth
Penelope
P
Gregory
Allison
A
Coryell
Jason
J
Westaway
Shawn K
SK
Gitschier
Jane
J
Das
Soma
S
Hayflick
Susan J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015835:Ocular Motility Disorders / Q000175:diagnosis* / Q000503:physiopathology; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000503:physiopathology; D015845:Tonic Pupil / Q000175:diagnosis* / Q000503:physiopathology
D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase