KSS is a multisystem disorder defined clinically by the triad of PEO and pigmentary retinopathy with onset before the age of 20 years plus at least one of: cardiac conduction block; cerebrospinal fluid (CSF) protein concentration greater than 0.1 g/L; cerebellar ataxia [76–80]. Frequent additional signs include sensorineural hearing loss, renal tubular acidosis, dementia, seizures, short stature and endocrine disturbance (diabetes mellitus, hypoparathyroidism and growth hormone deficiency). A progressive skeletal myopathy is also frequently seen. The most common magnetic resonance imaging (MRI) findings are cerebral and cerebellar atrophy with bilateral, often symmetrical, hyperintense lesions in the subcortical white matter, thalamus, basal ganglia and brainstem [81–83]. Interestingly, there appears to be little correlation between neurological deficits and the severity of the MRI features [84]. KSS is most commonly associated with single large-scale deletions of mtDNA [56]. We recently identified a case of KSS caused by nuclear genomic dysfunction due to mutations in RRM2B in a patient with multiple deletions of the mtDNA [85]. It is, therefore, possible for KSS to follow a Mendelian pattern of inheritance, although the majority of cases are sporadic.
PEO and pigmentary retinopathy
onset
before the age of 20 years
years
cerebrospinal fluid (CSF)
protein concentration
greater than 0.1 g/L
g/L