Lipoid Proteinosis with Homozygous ECM1 c.507del Variant and Functionally Significant Eyelid Involvement: A Case...

Lipoid proteinosis (LP), or Urbach-Wiethe disease, is a rare autosomal recessive disorder caused by pathogenic variants in ECM1. Early-onset hoarseness and moniliform blepharosis are characteristic, but diagnosis may be delayed when early airway findings are nonspecific or the mucocutaneous features are not considered together.

A 13-year-old male presented with hoarseness since infancy and a 2-year history of progressive bilateral upper-eyelid margin papules. Flexible nasopharyngolaryngoscopy at ages 1 and 2 years had been interpreted as congenital laryngomalacia. Repeat examination at age 10 was interpreted as chronic pharyngolaryngitis; vocal-cord mobility and closure were good and no neoplasm was identified. Examination at age 13 showed confluent waxy yellow-white papules along the upper eyelid margins, consistent with moniliform blepharosis, with partial eyelash loss, foreign-body sensation, and mild mechanical ptosis, together with oral mucosal thickening. Hematoxylin and eosin and periodic acid-Schiff staining demonstrated hyaline deposits in the papillary dermis. Whole-exome sequencing identified the homozygous ECM1 variant NM_004425.4:c.507del, p.(Arg171Glyfs*7), a previously reported recurrent pathogenic frameshift variant. Clinical, histopathological, and genetic findings jointly supported the diagnosis. Limited internal partial excision of the eyelid lesions improved ocular comfort. At follow-up on July 9, 2025, approximately 8 months after surgery, wound healing and eyelid contour were satisfactory.

Serial laryngoscopy with nonspecific findings does not exclude LP. Persistent childhood hoarseness accompanied by eyelid-margin papules should prompt clinicopathological correlation, with molecular testing used for etiological confirmation and genetic counseling. Functionally significant eyelid lesions may be managed with focused surgery when appropriate.