Phenotypic Expansion of Autosomal Dominant SREBF1-Related Ichthyosis Follicularis, Atrichia, Photophobia: It Is in Fact the Same Condition as Hereditary Mucoepithelial Dysplasia.

Variable expressivity of recurrent SREBF1 c.1579C>T (IFAP and HMD are the same entity)

Four new SREBF1-related IFAP patients all carry the recurrent variant NM_004176.5(SREBF1):c.1579C>T. Three presented gastrointestinal manifestations (GERD, esophageal strictures) not previously described in IFAP but reported in hereditary mucoepithelial dysplasia (HMD). Applying ClinGen Lumping and Splitting criteria demonstrates that IFAP and HMD very likely represent the same entity (variable expressivity of the same variant). The proposed unified name is SREBF1-sEDD.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Unifying two rare syndromic entities under a single nosological framework simplifies diagnostic classifications and genetic counseling. The GI phenotypic expansion is clinically useful: a SREBF1 patient with severe reflux or esophageal stenosis represents an HMD expression of the SREBF1-sEDD spectrum rather than an atypical phenotype.

Clinical impact: 2/3 · Evidence quality: 1/3 · Novelty: 2/2 · Sample size: 0/1 · Journal quality: 0/1 → Total: 5/10