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

Christine Prodinger; Subhanitthaya Chottianchaiwat; Jemima E. Mellerio; John A. McGrath; Linda Ozoemena; Lu Liu; William Moore; Martin Laimer; Gabriela Petrof; Anna E. Martinez

doi:10.1111/pde.14790

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

Christine Prodinger, Subhanitthaya Chottianchaiwat, Jemima E. Mellerio, John A. McGrath, Linda Ozoemena, Lu Liu, William Moore, Martin Laimer, Gabriela Petrof, Anna E. Martinez^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background/Objectives: 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: 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: 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: 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.

Original language	English
Pages (from-to)	1094-1101
Number of pages	8
Journal	Pediatric Dermatology
Volume	38
Issue number	5
DOIs	https://doi.org/10.1111/pde.14790
Publication status	Published - 1 Sept 2021

Keywords

blistering
epidermolysis bullosa
genetic disease
genodermatoses
hypergranulation

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10.1111/pde.14790

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@article{bd05488b8cc7493db17b300ccda06d5d,

title = "The natural history of laryngo-onycho-cutaneous syndrome: A case series of six pediatric patients and literature review",

abstract = "Background/Objectives: 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: 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: 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: 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.",

keywords = "blistering, epidermolysis bullosa, genetic disease, genodermatoses, hypergranulation",

author = "Christine Prodinger and Subhanitthaya Chottianchaiwat and Mellerio, {Jemima E.} and McGrath, {John A.} and Linda Ozoemena and Lu Liu and William Moore and Martin Laimer and Gabriela Petrof and Martinez, {Anna E.}",

year = "2021",

month = sep,

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doi = "10.1111/pde.14790",

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T1 - The natural history of laryngo-onycho-cutaneous syndrome

T2 - A case series of six pediatric patients and literature review

AU - Prodinger, Christine

AU - Chottianchaiwat, Subhanitthaya

AU - Mellerio, Jemima E.

AU - McGrath, John A.

AU - Ozoemena, Linda

AU - Liu, Lu

AU - Moore, William

AU - Laimer, Martin

AU - Petrof, Gabriela

AU - Martinez, Anna E.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Background/Objectives: 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: 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: 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: 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.

AB - Background/Objectives: 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: 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: 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: 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.

KW - blistering

KW - epidermolysis bullosa

KW - genetic disease

KW - genodermatoses

KW - hypergranulation

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DO - 10.1111/pde.14790

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SN - 0736-8046

VL - 38

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EP - 1101

JO - Pediatric Dermatology

JF - Pediatric Dermatology

IS - 5

ER -

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

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Keywords

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