Childhood-inherited white matter disorders with calcification

Area of Science:

• Neurology
• Genetics
• Radiology

Background:

• Intracranial calcification (ICC) is observed in various acquired and genetic neurological disorders.
• ICC is a significant diagnostic marker in certain inherited white matter diseases.
• Specific patterns of ICC can indicate particular diagnoses within this group.

Purpose of the Study:

• To detail the role of ICC in diagnosing specific inherited white matter disorders.
• To discuss Aicardi-Goutières syndrome (AGS), Coats plus (CP), and leukoencephalopathy with calcifications and cysts (LCC) in relation to ICC.
• To highlight the diagnostic value of ICC patterns in these conditions.

Main Methods:

• Review of clinical and neuroimaging features of AGS, CP, and LCC.
• Discussion of genetic underpinnings of AGS (interferon regulation), LCC (SNORD118), and CP (telomere function - CTC1, POT1, STN).
• Comparison of neuroimaging and neuropathologic findings in LCC and CP.

Main Results:

• AGS is linked to mutations in nine identified genes, affecting interferon regulation.
• LCC results from SNORD118 gene mutations, while CP involves CTC1, POT1, or STN gene mutations.
• LCC and CP exhibit similar neuroimaging and neuropathologic characteristics despite different genetic causes.

Conclusions:

• ICC is a crucial diagnostic clue for inherited white matter disorders.
• AGS, CP, and LCC are highlighted as key examples where ICC patterns are diagnostically informative.
• Understanding the genetic basis and clinical presentation associated with ICC aids in accurate diagnosis.