Overall, we observe some major features shared among the majority of patients with biallelic protein altering variants in PTPN23, namely developmental delay (100%), intellectual disability (100%), brain abnormalities (91%), mostly characterized by brain atrophy with cerebral volume loss, ventriculomegaly, and delayed myelination; tone or movement disorder (82%), language absence or delay (82%), microcephaly (63%), and optic atrophy (54%). Here, PTPN23 is linked to Leber hereditary optic neuropathy.