Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNHL) and early onset Retinitis Pigmentosa (RP) that may clinically overlap with Usher syndrome. Genetic testing by clinical exome sequencing identified two variants in PEX1: the missense variant c.274G > C; p.(Val92Leu) that was already reported in a PBD patient, and the variant c.2140_2145dup; p.(Ser714_Gln715dup) which is a novel, non-frameshift variant, absent in control databases. On the basis of the molecular analysis, a thorough clinical examination revealed nail and dental abnormalities, a mild cognitive impairment, learning disabilities and poor feeding, apart from the retinal and audiological features initially identified. The clinical and molecular findings led us to the diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes.
Keywords: ABR, Auditory Brainstem Responses; BCVA, Best Corrected Visual Acuity; CDI, Children’s Depression Inventory; ERG, full-field electroretinogram; Enamel defects; FAF, color fundus and fundus autofluorescence; GVF, Goldmann Visual Field; HS, Heimler syndrome; Mild Zellweger syndrome; OCT, optical coherence tomography; PBD, Peroxisomal biogenesis disorders; PEX genes; PEX, peroxin; PTA, Pure Tone Average; Peroxisomal biogenesis disorders; RP, retinitis pigmentosa; Retinitis pigmentosa; SNHL, sensorineural hearing loss; Sensorineural hearing loss; TEOAE, Transient-Evoked Otoacustic Emission; VLCFA, Very Long Chain Fatty Acid; WISC-IV, Wechsler Intelligence Scale for Children (4th Edition); ZS, Zellweger Syndrome; ZSD, Zellweger spectrum disorder.
© 2020 The Authors.