Clinical characteristics: Lipoid proteinosis (LP) is characterized by deposition of hyaline-like material in various tissues resulting in a hoarse voice from early infancy, vesicles and hemorrhagic crusts in the mouth and on the face and extremities, verrucous and keratotic cutaneous lesions on extensor surfaces (especially the elbows), and moniliform blepharosis (multiple beaded papules along the eyelid margins and inner canthus). Extracutaneous manifestations may include epilepsy, neuropsychiatric disorders, spontaneous CNS hemorrhage, and asymptomatic multiple yellowish nodules throughout the gastrointestinal tract. Generally, the disease course is chronic and fluctuating. Males and females are affected equally. Affected individuals have a normal life span unless they experience laryngeal obstruction.
Diagnosis/testing: The diagnosis of lipoid proteinosis is established in a proband with characteristic clinical findings and either biallelic ECM1 pathogenic variants identified on molecular genetic testing or characteristic histologic and/or immunolabeling findings on skin biopsy.
Management: Treatment of manifestations: There is no curative therapy for LP. Microlaryngoscopic excision of laryngeal deposits can improve airway access and voice quality. Significant airway obstruction may require tracheostomy to ensure a safe airway. Oral dimethylsulfoxide, D-penicillamine, and oral retinoid may be used for skin softening and amelioration of mucosal lesions and hoarseness. Seizures should be assessed and managed by a neurologist with anti-seizure medications.
Surveillance: Assessment of the airway and vocal cords by an otolaryngologist and dermatologic examinations every six months; yearly neurologic and neuropsychiatric evaluations for seizures and emotional and cognitive development.
Genetic counseling: LP is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an ECM1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants and being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the ECM1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
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