Abstract:
Background COL4A1/COL4A2 variants can cause a series of diseases such as porencephalia and cerebrovascular diseases, but there are few studies reporting that COL4A1/COL4A2 variants can be manifested as infantile spasms (IS).
Objective To summarize the clinical characteristics and prognosis of children with COL4A1/COL4A2 gene variants related IS, so as to furtherly improve clinicians' understanding to this disease.
Methods Clinical data and genetic test results of 6 children with COL4A1/COL4A2 gene variants who visited the pediatrics department of the First Medical Center of Chinese PLA General Hospital from May 2019 to August 2020 were analyzed retrospectively.
Results Among the 6 cases, there were 2 males and 4 females. The median age of onset was 6 months (range, 3-9 months). All the cases showed spastic seizures and the electroencephalography showed hypsarrhythmia, which were clearly diagnosed as IS. All the 6 cases were accompanied with different degrees of psychomotor developmental delay. Microcephaly were found in 5 cases, congenital cataract in 1 case, microphthalmia in 2 cases, elevated creatine kinase in 1 case, hemiplegia in 3 cases, and dyskinesia in 3 cases. All the 6 cases had abnormal findings on brain magnetic resonance imaging (MRI), manifested as ventriculomegaly, periventricular leukomalacia or volume reduction of cerebral white matter, and ventriculomegaly on brain MRI was found in fetus period of three cases. Five cases with COL4A1 variants were heterozygous de novo variants, including 2 cases of shear variants, c.3406 + 1 G＞T, c.280-1 G＞A, 3 cases of missense variants, c.4088G＞A, p. Gly1363Asp, c.2441G＞T p. Gly814Val, c.3968G＞A p. Gly1323Asp (NM_001845). One case was COL4A2 variant, c.1148C＞T p. Pro383Leu (NM_001846), a heterozygous de novo variant, and the variant type was missense variant. All the 6 cases had received the first-line treatment (adrenocorticotropic hormone, vigabatrin or oral cortisol) of IS, among which the onset of 1 case was controlled for more than 1 year after vigabatrin treatment, while the remaining 5 cases were not controlled. At the last follow-up, all the 6 cases had psychomotor developmental delay, among which 3 cases with COL4A1 variants had the worst motor and cognitive performance.
Conclusion COL4A1/COL4A2 gene is mainly de novo variants, which can be manifested as IS. For COL4A1/COL4A2 gene related IS, the brain MRI mainly presents as ventriculomegaly, periventricular leukomalacia or volume reduction of cerebral white matter, and some patients may develop brain MRI abnormalities in fetus period. In addition, patients may be accompanied by developmental delay, microcephaly, hemiplegia, dyspraxia and other system abnormalities, with poor prognosis.
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