Aicardi-Goutières syndrome (AGS) is a rare disorder characterized by acquired microcephaly, cerebral calcifications, leukodystrophy, cerebral atrophy, chronic lymphocytosis, and increased interferon-α in cerebrospinal fluid. We report on two children affected by AGS type 2, caused by mutations in RNASEH2B. The first child had the mutation c.529G > A (p.A177T) and presented with an atypical and mild phenotype, with delayed psychomotor development, calcifications of the brain white matter and basal ganglia, and interferon signature positivity. The disease course was stable. The second child presented the mutation c.554T > G (p.V185G) and showed a later onset (15 months) and a more progressive clinical course with functional inability in the upper limbs, steppage gait, and irritability. Despite immunoglobulin therapy, she developed to progressive tetraparesis and severe hypotonia. This case report highlights that RNASEH2B mutation cannot fully predict the phenotype of AGS type 2 when a mutation c.529G > A occurs. Moreover, an earlier symptomatology may be not related to a more severe prognosis or to a partial or absent response to treatment.

Aicardi-Goutières Syndrome Type 2: A Report on Two Cases with Different Phenotypes Caused by RNASEH2B Gene Mutations

Portale A.;Mazzurco M.;Portale L.;Polizzi A.;Pratico A. D.
;
Ruggieri M.
2020-01-01

Abstract

Aicardi-Goutières syndrome (AGS) is a rare disorder characterized by acquired microcephaly, cerebral calcifications, leukodystrophy, cerebral atrophy, chronic lymphocytosis, and increased interferon-α in cerebrospinal fluid. We report on two children affected by AGS type 2, caused by mutations in RNASEH2B. The first child had the mutation c.529G > A (p.A177T) and presented with an atypical and mild phenotype, with delayed psychomotor development, calcifications of the brain white matter and basal ganglia, and interferon signature positivity. The disease course was stable. The second child presented the mutation c.554T > G (p.V185G) and showed a later onset (15 months) and a more progressive clinical course with functional inability in the upper limbs, steppage gait, and irritability. Despite immunoglobulin therapy, she developed to progressive tetraparesis and severe hypotonia. This case report highlights that RNASEH2B mutation cannot fully predict the phenotype of AGS type 2 when a mutation c.529G > A occurs. Moreover, an earlier symptomatology may be not related to a more severe prognosis or to a partial or absent response to treatment.
Aicardi-Goutières syndrome
interferon signature
RNASEH2B
spastic paraparesis
type-I interferon
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/486864
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