Midface toddler excoriation syndrome (Mi TES ) can be caused by autosomal recessive biallelic mutations in a gene for congenital insensitivity to pain, PRDM 12

Summary Background Midface toddler excoriation syndrome (Mi TES ) is a condition recently reported in three unrelated children. Habitual scratching from the first year of life inflicted deep, chronic, scarring wounds around the nose and eyes. One child had a mild neurological deficit but there was no other evidence of insensitivity to pain. Bilateral distribution and localization to the midface distinguish Mi TES from other causes of self‐inflicted skin damage such as trigeminal trophic syndrome. An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to Mi TES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII ( HSAN 8), PRDM 12 . Objectives To study further cases of Mi TES , including analysis of PRDM 12 . Methods We describe five further children, from four families, with facial lesions typical of Mi TES , in whom mutation analysis of PRDM 12 was carried out. Results Homozygous or compound heterozygous pathogenic expansions of the PRDM 12 polyalanine tract were found in four of five affected individuals, in three families. Conclusions Our finding of autosomal recessive mutations in PRDM 12 in four of five patients with Mi TES extends the phenotypic spectrum of PRDM 12 mutations, which usually cause HSAN 8, characterized by mutilating self‐inflicted wounds of the extremities, lips and tongue. By contrast, Mi TES shows severe midfacial lesions with little if any evidence of generalized pain insensitivity. The condition is probably genetically heterogeneous, and other congenital insensitivity to pain and HSAN genes such as SCN 11A may be implicated. This new understanding of the nature of Mi TES , which can masquerade as factitious disease, will facilitate appropriate management.