Table 2

Selected conditions/syndromes to be considered in the differential diagnosis of isolated LCA/EOSRD

Condition/syndromeAssessments and features that assist in distinguishing from LCA/EOSRD
AchromatopsiaAchromatopsia 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 blindnessCan be differentiated on the basis of ERG phenotype and natural history.94
Ocular and oculocutaneous albinismClinical examination (skin, hair, eyebrows/eyelashes; iris and retina), retinal imaging (OCT and FAF) and electrophysiological assessment.
Optic nerve hypoplasiaClinical examination and electrophysiological assessment. Of note, absent pupil reflexes suggests severe optic nerve hypoplasia rather than LCA.
Batten diseaseInfantile 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 syndromePatients present with severe visual impairment, ocular motor abnormalities, often have the ‘molar tooth’ sign on MRI and develop nephronophthisis in later childhood.
Peroxisomal diseasesAssociated features include sensorineural deafness, dysmorphic features, developmental delay, hepatomegaly and early death.
Alstrom syndromePresents 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 deficiencyHas 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.