Intra-Familial Phenotypic Variability in Lipoid Proteinosis: A Case Series of Three Siblings.

Abstract

Lipoid proteinosis (LP), or Urbach-Wiethe disease, is an ultra-rare autosomal-recessive disorder caused by loss-of-function variants in the ECM1 gene. It is characterized by the progressive deposition of hyaline-like material in the skin, mucosae, and central nervous system. This series describes three siblings (aged 16, 24, and 25) from Gujranwala, Pakistan, born to non-consanguineous parents. All patients presented with infant-onset hoarseness of voice and recurrent vesiculobullous eruptions that evolved into waxy papules and hyperkeratotic plaques. Physical examination revealed the pathognomonic "beaded" eyelid papules (moniliform blepharosis), pock-like facial scarring, and a thickened lingual frenulum restricting tongue protrusion. Despite shared genetics, intrafamilial variability was observed, with the male sibling exhibiting a more severe "leonine-like" facies. Neuropsychiatric symptoms, including aggression and insomnia, were noted across the series. Due to resource constraints, the diagnosis was established clinically. Management focused on symptomatic control using oral acitretin (0.5 mg/kg/day), antihistamines, and intensive topical emollients. At 12-week follow-up, patients showed significant reduction in pruritus and stabilization of skin lesions, though hoarseness and established scarring remained unchanged. This series underscores the importance of recognizing cardinal clinical triads-moniliform blepharosis, mucosal tethering, and early hoarseness-to diagnose LP in resource-limited settings where genetic or histological confirmation is unavailable.