Biallelic Variants in TRAPPC11 Cause a Neurodevelopmental Disorder with Achalasia and Alacrima

Background/Purpose: Triple A syndrome (achalasia-addisonianism-alacrima syndrome) is primarily associated with pathogenic variants in the AAAS gene. However, some patients presenting with typical clinical features test negative for AAAS variants and remain without a molecular diagnosis. Pathogenic variants in TRAPPC11 have previously been described in limb-girdle muscular dystrophy type 18 (LGMDR18). A recent study identified a novel homozygous TRAPPC11 splice variant in four affected individuals suffering from achalasia, alacrima, as well as neurological and muscular symptoms. Clinical features were reminiscent of triple A syndrome but without affection of the adrenal gland. To describe a novel case of a TRAPPC11-related disorder with features of a "duo-A syndrome" (achalasia and alacrimia without addisonianism), caused by novel compound heterozygous variants, and to compare its clinical and genetic characteristics with previously reported cases.