LP is a multisystem disease due to multiple mutations in the ECM1 gene on chromosome 1 at 1q21.2 encoding extracellular matrix protein 1 (ECM1), present in the epidermis. This is a secretory glycoprotein expressed in the dermis and other tissues.⁴,⁸,⁹,¹⁰ More than 50 mutations in the ECM1 gene have been documented including missense, nonsense, frameshift, or splice site mutations with the majority occurring in exons 6 and 7.⁴,¹⁰,¹¹,¹²,¹³ Hamada et al¹⁴ reported that patients with mutations in exon 7 of the ECM1 gene tend to have a milder phenotype as compared with patients having mutations in other parts of the gene.

The ECM1 protein functions in epidermal differentiation, binding of dermal collagen and proteoglycans, and regulation of angiogenesis.¹⁵ Reduced expression of this protein results in aberrant deposition of eosinophilic hyaline-like material in the skin and viscera, leading to the clinical features of this disease.¹⁶,¹⁷

The clinical manifestations of LP involve respiratory, cutaneous, and neurologic tissues, but any organ can be involved. A hoarse cry is usually the first clinical sign, typically present at birth or shortly thereafter due to infiltration of the laryngeal mucosa.¹⁸,¹⁹,²⁰,²¹ Enlargement of the tongue with a thickened frenulum manifests as restricted tongue movements and is another reliable clinical sign of LP. In addition, there are yellow-white submucous infiltrates on other mucosal surfaces such as the pharynx, soft palate, and esophagus. Dental anomalies and dental caries also may be seen.¹⁶,²⁰ Skin lesions are a later finding appearing as blisters and erosions in early childhood and progressing to more distinct yellow waxy and warty papules and nodules, hyperkeratosis, facial and extremity spontaneous or trauma-induced acneiform or pocklike scars, and alopecia.²²,²³

Ocular manifestations can involve any part of the eye and ocular adnexa.²⁴ Moniliform blepharosis is considered a pathognomonic feature of LP and presents as small yellow-white beaded papules on the eyelid margins and skin (Figure 81.1).²⁵ Other less common ophthalmic findings include hyaline deposits on the iris, cornea, and the trabecular meshwork. Chorioretinitis, conjunctival nodules, uveitis, cataract, and lens subluxation are other possible findings.²⁶,²⁷,²⁸,²⁹ Focal degeneration of the macula and drusen formation in Bruch membrane is seen in about 30% to 50% of patients.²⁹ The lacrimal gland can be infiltrated with hyaline material resulting in dry eyes.²⁴ Open-angle glaucoma and retinitis pigmentosa have also been reported.²⁹ Infiltration of meibomian glands and glands of Zeiss and Moll is seen, often associated with madarosis, trichiasis, and sometimes
distichiasis.¹⁶,²⁴ Cystic punctal lesions and nasolacrimal duct obstructions are other rare complications of LP.²⁸,³⁰,³¹,³²,³³ Neurological manifestations usually present as migraines, seizures, mental retardation, anxiety, depression, and panic attacks,⁷ associated with intracranial calcifications within the amygdala or the temporal lobes.³⁴