General description

Urbach-Wiethe syndrome, also known as lipoid proteinosis or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder caused by mutations in the extracellular matrix protein 1 (ECM1) gene. This mutation leads to the deposition of collagenous material in the skin, mucosa, and other soft tissues, resulting in a wide range of clinical manifestations typically appearing in infancy or early childhood.

The skin is one of the most affected areas, with early symptoms including increased susceptibility to trauma and recurrent bullous impetigo. Over time, skin thickening occurs, especially on the face and in folds, resulting in waxy papules and plaques. A hallmark feature is moniliform blepharosis, characterized by multiple papules along the eyelid margins and inner canthus. Hyperkeratotic plaques may develop on frequently traumatized areas such as the elbows, and alopecia, dry or wrinkled skin, and poor wound healing are also common.

In the head and neck region, the disease often presents in infancy with a hoarse cry due to vocal cord stiffening. As it progresses, collagen deposition leads to thickened oral mucosa, macroglossia, and cobblestone-like lips, along with complications such as ankyloglossia, gum hypertrophy, dental hypoplasia, and recurrent infections of the parotid and submandibular glands. These changes may predispose patients to respiratory distress during upper respiratory infections.

Neurological involvement, including bilateral basal ganglia calcifications, may predispose to seizures, subtle cognitive impairments, and in rare cases, spontaneous intracerebral hemorrhage. Temporal lobe involvement can result in epilepsy, memory deficits, and psychiatric symptoms such as fearlessness, hallucinations, and delusions.

Despite the variety of symptoms, most patients maintain a normal lifespan. Anecdotal evidence suggests that skin manifestations may improve with acitretin, though its teratogenic risks necessitate cautious use in women of childbearing age.