The natural history of laryngo-onycho-cutaneous syndrome: A case series of six pediatric patients and literature review.


Journal

Pediatric dermatology
ISSN: 1525-1470
Titre abrégé: Pediatr Dermatol
Pays: United States
ID NLM: 8406799

Informations de publication

Date de publication:
Sep 2021
Historique:
pubmed: 14 9 2021
medline: 11 11 2021
entrez: 13 9 2021
Statut: ppublish

Résumé

Laryngo-onycho-cutaneous syndrome (LOC) is a rare subtype of junctional epidermolysis bullosa (JEB), featuring aberrant granulation tissue formation in the skin, larynx, and eyes. So far, three mutations including the specific (founder) mutation in exon 39 of LAMA3 (c.151dup) have been identified, but sparse data exists regarding the natural history, the genotype-phenotype correlation, and its differentiation from other JEB types. We reviewed our pediatric EB database to identify English children with clinical and genetically diagnosed LOC within the last 15 years. Their demographic, clinical, and laboratory data were examined. We searched three databases for case reports of LOC between January 1986 and November 2020 and extracted clinical and molecular details. We identified 6 LOC patients, all female (mean age 5.4 years). Periungual hypergranulation and skin fragility were the earliest presenting signs (0-3 months), followed by laryngeal stenosis, symblepharon (mean onset 10.7 and 11.8 months, respectively), and dental abnormalities. Five children developed anemia at an average of 19.2 months. We identified 22 published studies in English with 31 cases. This study delineates the disease course of LOC and highlights the overlap with some forms of JEB. Classical signs/symptoms including anemia appear early in life. Genetic analysis revealed three new LOC-associated variants and underscores the finding that interpretation of skin immunolabeling and molecular diagnostics can be challenging. We provide recommendations on management of this complex syndrome.

Sections du résumé

BACKGROUND/OBJECTIVES OBJECTIVE
Laryngo-onycho-cutaneous syndrome (LOC) is a rare subtype of junctional epidermolysis bullosa (JEB), featuring aberrant granulation tissue formation in the skin, larynx, and eyes. So far, three mutations including the specific (founder) mutation in exon 39 of LAMA3 (c.151dup) have been identified, but sparse data exists regarding the natural history, the genotype-phenotype correlation, and its differentiation from other JEB types.
METHODS METHODS
We reviewed our pediatric EB database to identify English children with clinical and genetically diagnosed LOC within the last 15 years. Their demographic, clinical, and laboratory data were examined. We searched three databases for case reports of LOC between January 1986 and November 2020 and extracted clinical and molecular details.
RESULTS RESULTS
We identified 6 LOC patients, all female (mean age 5.4 years). Periungual hypergranulation and skin fragility were the earliest presenting signs (0-3 months), followed by laryngeal stenosis, symblepharon (mean onset 10.7 and 11.8 months, respectively), and dental abnormalities. Five children developed anemia at an average of 19.2 months. We identified 22 published studies in English with 31 cases.
CONCLUSIONS CONCLUSIONS
This study delineates the disease course of LOC and highlights the overlap with some forms of JEB. Classical signs/symptoms including anemia appear early in life. Genetic analysis revealed three new LOC-associated variants and underscores the finding that interpretation of skin immunolabeling and molecular diagnostics can be challenging. We provide recommendations on management of this complex syndrome.

Identifiants

pubmed: 34514630
doi: 10.1111/pde.14790
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1094-1101

Informations de copyright

© 2021 Wiley Periodicals LLC.

Références

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Auteurs

Christine Prodinger (C)

Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Subhanitthaya Chottianchaiwat (S)

Department of Dermatology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.

Jemima E Mellerio (JE)

St. John's Institute of Dermatology, King's College London, Guy's Hospital, London, UK.

John A McGrath (JA)

St. John's Institute of Dermatology, King's College London, Guy's Hospital, London, UK.

Linda Ozoemena (L)

Viapath, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Lu Liu (L)

Viapath, Guy's and St Thomas' NHS Foundation Trust, London, UK.

William Moore (W)

Department of Ophthalmology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.

Martin Laimer (M)

Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Gabriela Petrof (G)

Department of Dermatology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.

Anna E Martinez (AE)

Department of Dermatology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.

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