Longitudinal Insights Into Polydactyly-Macrocephaly Syndrome: A Case Report of an Adult With a Recurrent MAX Variant

As genetic sequencing technologies-particularly whole-exome sequencing-have become readily accessible, their role has progressively shifted from identifying candidate genes for old or new syndromes to elucidating the etiology of ultra-rare disorders, where the population of affected individuals is frequently scarce and challenging to study. A newly described syndromic disorder, Polydactyly-Macrocephaly Syndrome (PMS), caused by a recurrent de novo variant in the MAX gene, has been reported in three individuals aged between 0 and 7 years. Here, we report a 19-year-old male with clinical follow-ups in our genetics unit since birth who carries the same recurrent MAX gene variant, along with glucose-6-phosphate dehydrogenase (G6PD) deficiency as a concurrent condition. Our findings provide valuable longitudinal insights into PMS variable expressivity and natural history and reinforce the recurrence of the c.179G>A (p.Arg60Gln) variant in all cases reported so far.