Expanded hexanucleotide repeats in C9ORF72 cause ALS and/or FTD inherited in an autosomal dominant pattern with incomplete penetrance. In families with both ALS and FTD the C9ORF72 repeat is the most common cause. There has been one case reported of a patient with FTD secondary to homozygous C9ORF72 repeat expansions from a consanguineous family whose parents had dementia. We present a case of a patient presenting with FTD at an early age who is heterozygous for two different hexanucleotide repeat expansions of the C9ORF72 gene.

A 46-year-old female presented to our behavioral neurology clinic for evaluation of cognitive deficits. During the clinic encounter she had minimal speech output and provided only short answers to questions.  Neurological exam was consistent with diffuse cerebral dysfunction with severe deficits in attention, cognitive processing speed, executive functioning and multiple aspects of language. Over one year she deteriorated to become mute and fully dependent in a facility.

Her family history is remarkable for both her father and mother dying of ALS. Genetic testing was positive for two different expanded C9ORF72 hexanucleotide repeat alleles. There is no evidence of consanguinity within this patients family. MRI brain showed diffuse parenchymal volume loss with prominence of frontal lobe sulci and preserved occipital lobes.

There has been one report of a patient who developed FTD inheriting an expanded repeat C9ORF72 allele from both parents who were affected with dementia. Both cases presented earlier than the mean age of onset of FTD but within the age range reported in C9ORF72 FTD cases and otherwise had consistent clinical features and disease course.