Common causes of ISs were excluded by brain magnetic resonance imaging (MRI), metabolic screening, array-comparative genomic hybridization (CGH) and testing for mutations in CDKL5, STXBP1, and for ARX duplications.
ARX is a crucial gene for the development of interneurons in the fetal brain, and a polyalanine expansion mutation of ARX causes mental retardation and seizures, including those of West syndrome, in males.
The striking epileptogenicity of X-linked lissencephaly with abnormal genitalia and West's syndrome associated with ARX mutations i s considered to be caused by a disorder of interneurons involving a tangentialmigration disorder.
Mutations in the Aristaless-related homeobox gene (ARX) lead to a range of X-linked intellectual disability phenotypes, with truncating variants generally resulting in severe X-linked lissencephaly with ambiguous genitalia (XLAG), and polyalanine expansions and missense variants resulting in infantile spasms.
We propose a core pathway of transcription regulators, including Hdac4, involved in chromatin condensation and transcriptional repression, and one of its targets, the transcription factor Twist1, as potential drivers of the ID and infantile spasms in patients with ARX polyalanine expansion mutations.
Aristaless-related homeobox gene (ARX) mutation leads to several neurological disorders including X-linked lissencephaly with abnormal genitalia (XLAG), West syndrome and Partington syndrome, with XLAG being the most severe form.
Polyalanine (polyA)-expansion-encoding mutations of aristaless-related homeobox (ARX) cause a spectrum of X-linked ID (XLID) diseases and chronic epilepsy, including infantile spasms.
Recently, we have shown that the majority of the X-linked families with infantile spasms carry mutations in the aristaless-related homeobox gene (ARX), which maps to the Xp21.3-p22.1 interval, and that the clinical picture in these patients can vary from mild mental retardation to severe ISSX with additional neurological abnormalities.
This combination of early infantile spasms followed by a complex movement disorder contributes further to extent the pleiotropy of the ARX-linked "interneuronopathy" and should lead the clinician to ARX mutation screening.
Autophagy-related X-linked BPAN disease might still be underdiagnosed in female cases of infantile spasms.Skewed X-inactivation will have mainly influenced the uncommon, very early childhood neurodegenerative symptomatology in the present BPAN case.
We report a case of partial biotinidase deficiency (plasma biotinidase levels: 1.30 nm/minute/mL) in a 7-month-old boy who presented with evidence of perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis.
While ACTH represents the first line of treatment for IS, the even higher efficiency of PMX53 (an antagonist of the complement C5a receptor) in restoring the normal transcriptome was not expected.
While ACTH represents the first line of treatment for IS, the even higher efficiency of PMX53 (an antagonist of the complement C5a receptor) in restoring the normal transcriptome was not expected.