In a child presenting with hoarseness, stridor, peri‑ungual hyper‑granulation with nail dystrophy, fragile skin erosions, and ocular granulation lesions, what is the likely diagnosis and how should it be managed?

Laryngo-Onycho-Cutaneous (Shabbir) Syndrome

The clinical presentation of hoarseness, stridor, periungual hypergranulation with nail dystrophy, fragile skin erosions, and ocular granulation lesions is diagnostic of Laryngo-Onycho-Cutaneous (LOC) syndrome, also known as Shabbir syndrome, a rare autosomal recessive subtype of junctional epidermolysis bullosa caused by mutations in the LAMA3 gene. 1, 2

Diagnostic Confirmation

Genetic testing for LAMA3 gene mutations is essential for definitive diagnosis, particularly the founder mutation c.151dup (151insG) in exon 39, which is most common in patients of Punjabi Muslim descent. 1, 3

• The mutation causes an N-terminal deletion of laminin alpha3a protein, disrupting keratinocyte-mesenchymal communication and leading to aberrant granulation tissue formation. 1
• Skin biopsy with immunohistological examination may reveal abnormal hemidesmosomes and weak immunoreactivity with antibodies against alpha-6-beta-4 integrin and basement membrane glycoproteins, similar to findings in junctional epidermolysis bullosa. 4
• However, genetic analysis is the gold standard, as skin immunolabeling can be challenging to interpret. 3

Clinical Course and Prognosis

The natural history follows a predictable but progressive pattern, with periungual hypergranulation and skin fragility appearing earliest (0-3 months), followed by laryngeal stenosis and symblepharon (mean onset 10.7 and 11.8 months respectively), dental abnormalities, and anemia (average onset 19.2 months). 3

• Laryngeal granulation tissue causing progressive airway obstruction is the most life-threatening complication, potentially leading to death if untreated. 2, 4
• Conjunctival granulation tissue progresses to symblepharon formation and can result in effective blindness. 4, 5
• All affected tissues demonstrate increased susceptibility to trauma. 4

Management Algorithm

Airway Management (Priority #1)

Immediate otolaryngology consultation is mandatory for any child with stridor or hoarseness, as laryngeal stenosis can be rapidly progressive and fatal. 2, 4

• Laser therapy (CO2 or similar) has been partially successful in alleviating laryngeal manifestations by removing granulation tissue. 4
• Tracheostomy may be required for severe airway obstruction and has been life-saving in reported cases. 2, 5
• Serial laryngoscopy is necessary to monitor for recurrent granulation tissue formation. 3

Ocular Management

Topical corticosteroid drops are effective for treating early ocular surface granulation lesions and should be initiated promptly upon detection. 5

• Regular ophthalmology follow-up is critical to detect and treat frequent granulation tissue outgrowth before severe symblepharon and blindness develop. 5
• Mean onset of symblepharon is 11.8 months, emphasizing the need for early and consistent monitoring. 3

Dermatologic and Nail Care

Meticulous wound care is essential for fragile skin erosions, with focus on preventing secondary infection and minimizing trauma. 3, 4

• Daily topical emollients to cuticles and periungual tissues help maintain nail health despite dystrophy. 6
• Periungual hypergranulation requires gentle debridement and protective measures to prevent further trauma. 3
• Avoid activities that increase skin trauma risk. 4

Systemic Monitoring

Screen for anemia starting in infancy, as it develops in the majority of patients by approximately 19 months of age. 3

• Monitor for dental enamel hypoplasia and provide appropriate dental care. 3, 4
• Nutritional support may be necessary if feeding difficulties develop secondary to oral or laryngeal involvement. 3

Critical Pitfalls to Avoid

Do not delay genetic testing or specialist referrals, as early diagnosis allows for proactive management of life-threatening complications. 2, 3

• Never dismiss stridor or hoarseness as benign, as laryngeal stenosis can progress rapidly to fatal airway obstruction. 2, 4
• Do not confuse LOC syndrome with other forms of junctional epidermolysis bullosa—while there is overlap, the specific pattern of granulation tissue formation distinguishes LOC. 3, 4
• Avoid assuming this is fungal onychomycosis based on nail appearance alone; the constellation of findings (especially laryngeal and ocular involvement) points to LOC syndrome. 7, 1
• Regular follow-up across multiple specialties (ENT, ophthalmology, dermatology, genetics) is non-negotiable to prevent progression to blindness or death. 3, 5

Genetic Counseling

Provide autosomal recessive inheritance counseling to the family, with 25% recurrence risk for future pregnancies. 1, 2

• The condition is particularly prevalent in the Punjabi Muslim population due to a founder mutation. 1, 4
• Prenatal genetic testing is available for at-risk pregnancies once the familial mutation is identified. 1