Phenotypic variability in Arboleda-Tham syndrome: a report of a polish patient with a pathogenic KAT6A variant.

backgroundArboleda-Tham syndrome (ARTHS) is caused by heterozygous pathogenic or likely pathogenic variants in the KAT6A gene. The main reported features include developmental delay, dysmorphism, low-set posteriorly rotated ears, a prominent nasal bridge, epicanthal folds, hypotonia, poor speech development, feeding difficulties, and cardiovascular anomalies. CASE: The proband is a 6 year old boy with global developmental delay, who reaches developmental milestones significantly later than expected. He was born to healthy parents, and diagnostic evaluation began at 18 months of age. A pathogenic, de novo, nonsense variant, c.3055C>T (p.Arg1019Ter), was identified in the KAT6A gene. The patient's clinical features were attributed to a diagnosis of ARTHS.

conclusionThis report underscores the value of genomic sequencing in establishing an accurate diagnosis even when the full clinical picture of ARTHS is not present. By providing clinical documentation across several years, our case broadens the recognized phenotypic spectrum of ARTHS and contributes to a deeper understanding of KAT6A-related phenotypic variability and natural history.