27 year old gentleman with normal birth and development presented with drowsiness and ataxia following a febrile illness. Followed by patient developed psychiatric manifestations including suicidal tendencies. MRI Brain suggestive symmetrical basal ganglionic T2 hyper-intensities. Family history suggestive of almost similar complaints in both the elder sisters at an early age.
Thirty four year old first sibling with normal birth and delayed development in all domains suddenly worsened since last 2 years developed gait ataxia with psychiatric manifestations, urinary and fecal incontinence. On examination cerebellar ataxia and absent DTR were present. MRI Brain suggestive of diffuse symmetrical cerebellar atrophy with T2 hyperintensities in bilateral cerebral peduncles.
Thirty year old second sibling with normal and initial development, had sudden onset recurrent falls and ataxia at the age of 3 years followed by rapid worsening which led to bed ridden status. Within few years with severe truncal hypotonia. MRI Brain suggestive of symmetrical T2 hyperintensities in putamen and caudate.
Whole genome exome sequencing of the third sibling revealed autosomal dominantly inherited heterozygous mutation in ATAD3A gene on chromosome 1 causing a rare distinct syndrome Harel-yoon Syndrome. The same gene mutation was targeted in family members which was present in father and elder sister. Due to variable penetration of autosomal dominantly disorders, variable age and symptoms presentation had seen .