Two siblings presented with spastic paraplegia and psychomotor retardation with or without seizures with HACE1 variants: A case report and literature review.
Jiong Deng, Yuheng Gao
✦ AI-curated · Sources linked
Case in brief
Two siblings from a nonconsanguineous Chinese family had infantile-onset hypotonia, global developmental and motor delay, gait impairment, language delay, and dysarthria; the older sister also had recurrent febrile seizures, while her brother had none. Whole-exome sequencing, confirmed by Sanger sequencing, found the same compound heterozygous HACE1 variants in both: a paternal c.1303C > T (p.Gln435Ter) variant and a maternal c.2158_2159insG (p.Glu720GlyfsTer17) variant. With symptomatic rehabilitation and follow-up, both achieved independent walking but remained unable to run, with persistent dysarthria and substantial cognitive impairment.
What made this case unusual
The siblings shared the same HACE1 variants but differed in seizure history. Their long-term course included independent walking and some communication with short phrases, despite persistent motor and cognitive limitations.
Diagnostic / clinical pearl
In a child with early hypotonia, developmental delay, and gait impairment, biallelic HACE1 variants can establish SPPRS; seizure history may differ even between affected siblings.
Why it matters
Molecular diagnosis can support individualized rehabilitation and inform genetic counseling and prenatal diagnostic planning.