Novel WDR45 mutation causing beta-propeller protein associated neurodegeneration (BPAN) in two monozygotic twins

Beta‐propeller protein‐associated neurodegeneration: a case report and review of the literature

“…A total of 64 patients were included in the analysis, comprising 55 women (85.9%) and nine men (14.1%) (Tables and ) . Mean age at diagnosis was 27.6 ± 14 years (range 1–52), and mean age at deterioration was 27.2 ± 5.7 (range 13–39).…”

“…Definite data were only available for 16 of 64 patients (25%) of whom 11 (68.8%) were reported to have dysmorphic features. These included microcephaly , abnormal nasal bridge (depressed, high, wide, and flat) , a small mouth , tented upper lip , hypertelorism , epicanthal folds , downslanting palpebral fissures , large ears , bilateral low‐set ears , low hanging columella , short philtrum , high palate , downturned mouth and micrognathia , narrow face , narrow nose , thin upper lip , kyphosis , flat and almost rocker bottom feet , fingers tapered with fifth finger clinodactyly , partial synophrys , and congenital talipes varus . Small cold hands and feet were also reported .…”

WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis

“…Among them, the autophagy gene WDR45 (also known as WIPI4) was critical for the formation of the autophagosome ( Bakula et al, 2017 , 2018 ). Mutations in WDR45 were found to be associated with a human neurodegenerative disorder, namely, β-propeller protein-associated neurodegeneration (BPAN, OMIM 300894), which is an X-linked neurodegenerative disorder characterized by a childhood onset of intellectual impairment followed by a second period of deterioration in adulthood ( Araujo et al, 2017 ). Brain MRI of BPAN patient presents an iron accumulation in the globus pallidus and substantia nigra ( Haack et al, 2012 ).…”

Single-center experience with Beta-propeller protein-associated neurodegeneration (BPAN); expanding the phenotypic spectrum

“…Thinning of the corpus callosum has also been observed [4,5,11,18] and was present in patient #1. Additionally, in many reported cases with BPAN, hyperintense signals on T1-weighed images were observed surrounding regions of iron deposition [3,4,6,[19], [20], [21]]. However, abnormal T1 signals were not observed in any of the five cases described herein.…”

“…The absence of iron accumulation in the globus pallidus and substantia nigra in early childhood brain MRI with its appearance later, either with standard or specialized MRI techniques, as was the case in patients #1 and #2, has been previously observed [[9], [10], [11],[15], [16], [17]]. Iron accumulation in the basal ganglia has been reported as early as 3 years of age using susceptibility-weighted imaging [18] and it has been observed as early as 8 years using standard T2 weighted imaging [19]. Additionally, some patients have had varying degrees of cerebral or cerebellar atrophy on brain MRI [4], as was observed in patients #2 and #5.…”