Severe early-childhood-onset retinal dystrophy (ORPHA:364055)
Severe early childhood onset retinal dystrophy (SECORD) is an inherited retinal dystrophy characterized by a severe congenital night blindness, progressive retinal dystrophy and nystagmus. Best corrected visual acuity can reach 0.3 in the first decade of life and can pertain well into the second decade of life. Blindness is often complete by the age of 30 years.
Epidemiology
The prevalence is hard to predict as many SECORD patients have been previously diagnosed as Leber congenital amaurosis (LCA) patients.
Clinical description
SECORD occurs during childhood and covers patients with severe congenital night blindness, nystagmus, a significantly reduced visual acuity (less or equal than 0.3) along with a progressive panretinal dystrophy of diverse extent and affection of the macula. The first symptoms can be recognized in the first year of life. Color vision is impaired in saturated and desaturated tests. An overlap with Leber congenital amaurosis (LCA) occurs when patients are characterized by their visual acuity and panretinal dystrophy. However, compared to LCA, the visual function in SECORD is much better, despite the progressive loss of visual function early in the disease that can lead to blindness in the second to third decade of life, depending on the underlying gene and mutation.
Etiology
SECORD is genetically heterogeneous, being caused by many genes including those causing LCA (ABCA4 (1p22), ADAMTS18 (16q23), AIPL1 (17p13.1), BEST1 (11q12), CRB1 (1q31.3), CRX (19q13.3), GUCY2D (17p13.1), IMPDH1 (7q31.3-q32), IMPG1 (6q14.2-q15), IMPG2 (3q12.2-q12.3), IQCB1 (3q21.1), KCNJ13 (2q37), LCA5 (6q14), LRAT (4q32.1), MERTK (2q14.1), NMNAT1 (1p36.22), RDH12 (14q24.1), RPE65 (1p31), RPGR (Xp11.4), RPGRIP1 (14q11.2), SPATA7 (14q31.3), TULP1 (6p21.3)). SECORD has however been primarily associated with mutations in RPE65 (2-10% of SECORD patients) and LRAT.
Diagnostic methods
Diagnosis of SECORD includes rod and cone responses below or near threshold in electroretinography. Psychophysical testing predicts cone-rod and rod-cone dystrophies. Patients may show a normal appearing fundus at birth but develop a panretinal dystrophy including the macula later in infancy and early childhood. Corresponding alterations of retinal layers are seen with spectral domain optical coherence tomography. A lack of fundus auto fluorescence is observed from early childhood in a subset of patients with RPE65 or LRAT mutations. Goldmann perimetry reveals severe visual field constriction and central scotomata depending on the type of progression. Bone spicules are usually not detected but pigment accumulations develop with the progress of the disease. Molecular diagnosis is performed by using next generation sequencing panel covering the whole sequence of the known reported genes (90% cases). Identified mutations and segregation analysis in the parents is confirmed by Sanger sequencing.
Differential diagnosis
Differential diagnosis includes LCA, Alström syndrome, autosomal recessive bestrophinopathy, Bardet-Biedl syndrome, achromatopsia, Stargardt disease, Usher syndrome, Senior-Loken syndrome, Saldino-Mainzer syndrome, Joubert syndrome, abetalipoproteinemia, infantile Refsum disease, neonatal adrenoleukodystrophy, Zellweger syndrome and juvenile neuronal ceroid lipofuscinosis.
Genetic counseling
SECORD is usually inherited in an autosomal recessive manner but autosomal dominant (CRX, GUCY2D, IMPDH1, IMPG1, IMPG2) and X-linked inheritance have also been observed.
Management and treatment
SECORD is currently incurable and therapies are being investigated, including gene therapy for RPE65, ABCA4 and MERTK. Retinoid supplementation therapy (9-cis-retinoid) is used for patients with mutations in RPE65 and LRAT. Treatment is supportive and includes correction of refractive error and use of low-vision aids.
Prognosis
The visual performance in bright light permits attendance at regular schools during the elementary years. Due to the genetic heterogeneity, a broad spectrum of progression exists that does not correlate with specific mutations. Useful visual function is frequently preserved beyond the second decade of life and a number of patients retain residual islands of peripheral vision, albeit considerably compromised, in the third decade of life.

                            Last update: 
                            December 2017


                            - Expert reviewer(s): 
                            Pr Birgit LORENZ  - Dr Markus PREISING