Abstract
INTRODUCTION: TUBGCP6-related disorder is a known cause of autosomal recessive microcephaly and chorioretinopathy, which was originally recognized as a new syndrome based on unique ocular findings on a phenotypic overlap of microcephalic primordial short stature. Since the elucidation of its molecular mechanism, limited families have been published in literature and the disorder remains rare worldwide. CASE PRESENTATION: We present the first Indian family with an affected child and sibling fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain imaging in both and short stature, intellectual disability, and visual impairment in proband. As for many patients with long diagnostic odysseys, this child also underwent multiple genomic tests. Genome sequencing through the Indian Undiagnosed Disease Program (I-UDP) confirmed the diagnosis in both proband and sibling fetus. Compound heterozygous variants were identified in TUBGCP6 including an eleven base pair deletion (inherited from father) and 405 base pair large deletion (inherited from mother). Reverse phenotyping to confirm the ocular phenotype in proband confirmed TUBGCP6-related microcephaly and chorioretinopathy. We report third trimester microcephaly with ventriculomegaly and abnormal sulcation as part of the antenatal presentation for this condition. CONCLUSION: This case represents an Indian family with a seemingly obvious clinical diagnosis compounded by a long diagnostic odyssey and the first ever structural variant to be identified via whole genome sequencing in TUBGCP6 in trans with an indel variant.