Selected conditions/syndromes to be considered in the differential diagnosis of isolated LCA/EOSRD.
| Condition/syndrome | Assessments and features that assist in distinguishing from LCA/EOSRD |
| Achromatopsia | Achromatopsia is characterised by absent/markedly reduced cone responses with normal rod ERG responses and a stationary natural history; compared with the flat/markedly reduced full-field ERGs and progressive degeneration seen in LCA/EOSRD. |
| Congenital stationary night blindness | Can be differentiated on the basis of ERG phenotype and natural history.94 |
| Ocular and oculocutaneous albinism | Clinical examination (skin, hair, eyebrows/eyelashes; iris and retina), retinal imaging (OCT and FAF) and electrophysiological assessment. |
| Optic nerve hypoplasia | Clinical examination and electrophysiological assessment. Of note, absent pupil reflexes suggests severe optic nerve hypoplasia rather than LCA. |
| Batten disease | Infantile Neuronal Ceroid Lipofuscinosis (NCL) presents with congenital or early- onset blindness, with onset by age 6 months; whereas patients with Late and Juvenile onset NCL present at 2–4 and 6 years of age or older, respectively. Patients with NCL have neurocognitive decline and can have epilepsy. |
| Joubert syndrome | Patients present with severe visual impairment, ocular motor abnormalities, often have the ‘molar tooth’ sign on MRI and develop nephronophthisis in later childhood. |
| Peroxisomal diseases | Associated features include sensorineural deafness, dysmorphic features, developmental delay, hepatomegaly and early death. |
| Alstrom syndrome | Presents with infantile onset nystagmus, photophobia and a cone–rod dystrophy on electrophysiological assessment. Other systemic features include childhood obesity, hyperinsulinaemia, type 2 diabetes mellitus, hepatic dysfunction, heart failure, sensorineural hearing loss and renal failure. |
| Cobalamin C deficiency | Has a variable phenotype with severely affected individuals showing progressive, infantile onset, metabolic, neurological and ophthalmic manifestations, including infantile nystagmus, bulls-eye maculopathy and reduced responses on ERG. |
EOSRD, early-onset severe retinal dystrophy; FAF, fundus autofluorescence; LCA, Leber congenital amaurosis; OCT, optical coherence tomography.