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Published on: March 24, 2019
Early Phenotypic Features of Beta-Propeller Protein-Associated Neurodegeneration: Insights From a Korean Series
Yun Soo Kim1, Soo-Yeon Kim2, Yun-Jin Lee3
1Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea.
Insights
Beta-propeller protein-associated neurodegeneration (BPAN) is a rare genetic disorder. Early recognition in children is aided by identifying developmental delay and specific MRI findings, even before advanced symptoms appear.
Area of Science:
- Neuroscience
- Genetics
- Pediatrics
Background:
- Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked disorder.
- Pathogenic variants in the WDR45 gene cause BPAN.
- Early diagnosis is difficult due to nonspecific childhood presentations.
Purpose of the Study:
- To identify early clinical features of BPAN in pediatric patients.
- To improve early recognition of BPAN in children.
- To correlate WDR45 variants with clinical and imaging findings.
Main Methods:
- Retrospective analysis of six pediatric BPAN patients.
- Genetic testing for WDR45 variants.
- Clinical assessment including neurodevelopmental evaluation.
- Brain MRI and serum neuron-specific enolase level analysis.
Main Results:
- All six patients were female with early developmental delay and severe language impairment.
- Seizures and motor dysfunction were common; two patients had central precocious puberty.
- Brain MRI showed corpus callosum thinning in all cases.
- Iron accumulation in substantia nigra/globus pallidus was seen in older patients.
Conclusions:
- Early clinical features like developmental delay and language impairment can suggest BPAN.
- Corpus callosum thinning on MRI is an early indicator.
- Identifying these features aids in earlier diagnosis, preceding distinctive MRI changes or degenerative signs.
Abstract:
Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked disorder caused by pathogenic variants in the WDR45 gene. Early diagnosis remains challenging because of nonspecific presentations in childhood. We report six pediatric patients with BPAN identified through genetic testing performed during evaluations of neurodevelopmental disorders. All the participants were female and exhibited early developmental delay, severe language impairment, and varying degrees of motor dysfunction. Seizures occurred in four patients with varying severity. Two patients showed signs of central precocious puberty. Serum neuron-specific enolase levels were elevated in all tested patients. Brain magnetic resonance imaging (MRI) revealed corpus callosum thinning in all the patients. Iron accumulation in the substantia nigra and globus pallidus was observed in only two older patients. WDR45 variants included two nonsense mutations, two splice sites, one in-frame deletion, and one novel frameshift deletion. Our findings highlight early clinical features that may aid in recognizing BPAN prior to the emergence of distinctive MRI abnormalities or degenerative-phase manifestations.
