Macular Dystrophy with Bilateral Macular Telangiectasia Related to the CYP2U1 Pathogenic Variant Assessed with Multimodal Imaging Including OCT-Angiography

Abstract

Purpose: We report the case of a neurologically asymptomatic young boy presenting with an unusual phenotype of CYP2U1 related macular dystrophy associating bilateral macular telangiectasia (MacTel) and fibrotic choroidal neovascularization (CNV), assessed with complete multimodal imaging including optical coherence tomography angiography (OCT-A). Case presentation: A twelve-year-old boy from a non-consanguineous family complained of bilateral progressive visual loss and photophobia. The best-corrected visual acuity was 2/10 on the right eye and 3/10 on the left eye. Fundus examination showed central pigmented fibrotic macular scar and yellowish punctuate deposits in both eyes. En face OCT-A detected typical macular telangiectasia (MacTel) in both eyes with dilated telangiectatic capillaries in the deep capillary plexus associated with vascular anomalies in the superficial and deep capillary plexus. Typical hypo-reflective cavities were observed within the inner foveal layers on structural OCT. En face OCT-A also confirmed the presence of bilateral inactive CNV within the fibrotic scars, showing high-flow vascular network at the level of the subretinal hyperreflective lesions. Whole exome sequencing identified a known homozygous pathogenic variant in CYP2U1 gene (c.1168C > T, p.Arg390*), which is a disease-causing mutation in autosomal recessive spastic paraplegia type 56 (SPG56). The neurological examination was normal, and electromyography and brain magnetic resonance imaging were unremarkable as well. Conclusion: Macular dystrophy can be the first manifestation in SPG56. A particular phenotype with MacTel was observed, and neovascular complications are possible. CYP2U1 should be included in the panels of genes tested for macular dystrophies, especially in the presence of MacTel and/or neurological manifestations.

Hereditary spastic paraplegia type 56: what a mouse can tell - a narrative review

“…In a French family included in our cohort, [12] the same CYP2U1 pathogenic mutation was observed leading to an extremely severe disability affecting both lower and upper limbs, starting before the first year of age, and accompanied by intellectual disability. In contrast with the other cases reported, carrier members belonging to a Tunisian family recently reported by El Matri et al [13] did not present any symptoms at neurological examination (age at examination: 12 years of age) but manifested visual deficits, similar to those observed in the Italian patients.…”

“…Interestingly, CYP2U1 mutations have also recently been implicated in a neurocutaneous syndrome, [15] and it has also been suggested that they could affect the retina, leading to macular dystrophy. [13,[15][16][17] As often observed in HSPs, a huge intra-and inter-familial variability characterize the severity of symptoms presented by SPG56-HSP patients, even among those sharing the same causative mutation. A clear example of this phenomenon is provided by three families sharing a stop mutation (p.Arg390X) leading to the premature termination of CYP2U1 translation.…”

“…SPG56-HSP is one of the least frequent HSP subtypes (prevalence <1/1,000,000), estimated affecting 1.5% of HSP patients. [10] So far mutations in CYP2U1 have been detected in 54 carrier patients, [10,[12][13][14] with an equal repartition between men (28/54, 52%) and women (25/54, 46%) (Fig. 1A).…”

“…[12] Finally, as in other HSP mice models, [8] Cyp2u1 -/mice did not display any significant locomotor impairment in the used behavioral tests. [16] El Matri et al, [13] and Pujol et al [12] ♀=woman, ♂=man, HSP=hereditary spastic paraplegia, LL=lower limbs, UL=upper limbs, yr=years old.…”

“…1C). Interestingly, CYP2U1 mutations have also recently been implicated in a neurocutaneous syndrome, [15] and it has also been suggested that they could affect the retina, leading to macular dystrophy [13,15–17] …”