Clinical Guidance
The phenotypic spectrum of CLCN2-related leukoencephalopathy ranges from childhood onset with mild ataxia, learning disabilities, and headaches to adult onset with mild ataxia and decreased vision . Infertility or involuntary childlessness in adulthood has been observed in four adult males [; Authors, personal observation]. Several individuals with psychiatric concerns (depression or psychosis) and/or auditory abnormalities including mild hearing loss, tinnitus, and vertigo have been observed. Other medical concerns occurring in a few individuals may be rare parts of the phenotype or unrelated findings. The disease course has been reported as stable to slowly progressive; considering that adults were previously normal, extremely slow progression is most likely. All individuals reported to date have remained ambulatory. The oldest known individual with CLCN2-related leukoencephalopathy is age 70 years. No disease-related deaths have been reported to date. To date, 31 individuals have been identified with biallelic pathogenic variants in CLCN2 [; ; ; ; ; ; ; ; ; ; Authors, personal observation]. The following description of the phenotypic features associated with this condition is based on these reports and personal observations. Table 2. CLCN2-related Leukoencephalopathy: Frequency of Select Features
Feature | # of Personswith Feature1 | Comment |
|---|
Mild cerebellar ataxia | 18/30 | — |
Mild spasticity | 2/29 | — |
Mild cognitive impairment | 14/28 | — |
Psychiatric symptoms | 7/29 | Incl depression psychosis/schizophrenia-like symptoms |
Headache | 12/28 | — |
Decreased vision | 8/25 | Incl retinopathy optic atrophy; blindness double vision may occur. |
Auditory abnormalities | 8/29 | Incl (mild) hearing loss, tinnitus, dizziness |
Male fertility problems | 4/4 | Not all affected males have been assessed for infertility. Involuntary childlessness in adult males was included in this category. 1. Motor skills. Initial motor development is normal. |
Source: GeneReviews — "CLCN2-Related Leukoencephalopathy"
