Fig. 2: Clinical features of the affected individuals with biallelic AIRIM variants.

a, Summary of global developmental delay and microcephaly in aggregated published individuals to date. b, Brain MRI of the 1-year and 11-month-old proband in family 4 (II:2). Sagittal T2-weighted image (WI), axial T2WI and axial T1WI showing atrophy in the supratentorial compartment of the brain, including a diffusely thin corpus callosum (arrow) and enlargement of the extra-axial spaces. Abnormal T2WI hyperintensity of the deep and superficial white matter with relatively normal myelination appearance along the anterior and posterior limbs of the internal capsules, as well as the optic tracts (arrowheads). Brain MRI of the sibling of the proband in family 5 (II:3) showing severe atrophy in the supratentorial compartment of the brain, including a diffusely thin corpus callosum (arrow) and enlargement of the extra-axial spaces. Abnormal T2WI hyperintensity of the deep and superficial white matter with relatively normal myelination appearance along the anterior and posterior limbs of the internal capsules, as well as the optic tracts (arrowheads). It is also important to note the relatively normal appearance of the overall structures of the posterior fossa with normal volume, morphology and myelination appearance of the cerebellum. Brain MRI of the proband in family 6 (II:1) at 6 months old; sagittal T1WI, axial T2WI and axial T1WI. Severe atrophy in the supratentorial compartment of the brain, including a diffusely thin corpus callosum (arrows) and diffuse enlargement of the extra-axial spaces with bilateral under-opercularization of Sylvian fissures. Abnormal T2WI hyperintensity of the deep and superficial white matter with relatively normal myelination appearance along the anterior and posterior limbs of the internal capsules, as well as the optic tracts (arrowheads). It is also important to note the relatively normal appearance of the overall structures of the posterior fossa with normal volume, morphology and myelination appearance of the cerebellum. Brain MRI of the proband in family 9 (II:3) showing severe atrophy in the supratentorial compartment of the brain, including a diffusely thin corpus callosum (arrow) and enlargement of the extra-axial spaces. Abnormal T2WI hyperintensity of the deep and superficial white matter with relatively normal myelination appearance along the anterior and posterior limbs of the internal capsules, as well as the optic tracts (arrowheads). It is also important to note the relatively normal appearance of the overall structures of the posterior fossa with normal volume, morphology and myelination appearance of the cerebellum. c, Bar graphs summarizing the comparative proportions of various clinical findings in individuals with AIRIM, AFG2B and AFG2A variants. Dys., dysmorphic facial features; GDD/ID, global developmental delay/intellectual disability; GI, gastrointestinal issues; MH/LS/D, muscular hypotonia/limb spasticity/dystonia; MIC, microcephaly.