Retinopathy and neurodegeneration with brain iron accumulation due to DDHD1 mutations, by Dard et al, Eur J Med Genet 2017

Defects of phospholipids remodelling and synthesis are inborn errors of metabolism responsible for various clinical presentations including spastic paraplegiaretinopathy, optic atrophy, myo- and cardiomyopathies, and osteo-cutaneous manifestations. DDHD1 encodes a phospholipase A1, which is involved in the remodelling of phospholipids. We previously described a relatively pure hereditary spastic paraplegia (HSP) phenotype associated with mutations in DDHD1. Here we report a complex form of HSP associated with retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation (NBIA) on brain MRI, due to a novel homozygous mutation in DDHD1. This observation enlarges the clinical spectrum of DDHD1-associated disorders and sheds light on a new aetiology for syndromes associating retinopathy and NBIA. It also emphasizes the role of complex lipids in the retina.

 

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Figure: Ophthalmic findingsOculus fundi (A) showing optic disc pallor, astrocytichamartoma visible in the inferior part of the right optic disc, narrowed retinalvessels, peripheral mottled appearance of the retinal pigment epithelium. Humphrey visual fields (B) showing defects that involve both peripheral and central vision in both eyes, worse in the right eye. Fundus autofluorescence images (C), showing perifoveal hyperautofluorescent ring surrounded by hypo-autofluorescent retina. SD-OCT (D) section demonstrating the loss of inner and outer photoreceptorsegments in the corresponding area outside the ring. Electroretinogram performed with the ISCEV standard for full-field clinical electroretinography (E: Dark-adapted 0.01 ERG (rod), F: Light-adapted 3.0 ERG (cone), G: Dark-adapted 3.0 (combined rod-cone)) showing generalized retinal dysfunction at the level of photoreceptors (E,F) in keeping with generalized rod-cone dysfunction (blue line: normal response, green line: the patient). Inner retinal level is normal with the absence of electronegative aspect on the Dark-adapted 3.0 (G). VFI: visual field index; MD: mean deviation; PSD: pattern standard deviation; TEMP: temporal; SUP: superior; NAS: nasal; OS: oculus sinister (left eye); OD: oculus dexter (right eye). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)