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Laryngo-onycho-cutaneous syndrome(JEB2C)

MedGen UID:
272227
Concept ID:
C1328355
Disease or Syndrome
Synonyms: EPIDERMOLYSIS BULLOSA, JUNCTIONAL 2C, LARYNGOONYCHOCUTANEOUS; JEB2C; Laryngoonychocutaneous syndrome; Logic syndrome
SNOMED CT: Laryngo-onycho-cutaneous syndrome (722675000); LOC syndrome (722675000); LOGIC syndrome (722675000); Laryngoonychocutaneous syndrome (722675000); Shabbir syndrome (722675000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LAMA3 (18q11.2)
 
Monarch Initiative: MONDO:0009513
OMIM®: 245660
Orphanet: ORPHA2407

Definition

Junctional epidermolysis bullosa 2C (JEB2C), also known as laryngoonychocutaneous syndrome (LOCS), is an autosomal recessive disorder characterized by skin erosions, nail dystrophy, dental anomalies, and excessive vascular granulation tissue of the conjunctiva and larynx. Onset is characterized by a hoarse cry soon after birth. Beginning in infancy, chronic skin ulcers and conjunctival lesions appear. Patients may die in childhood secondary to acute or chronic respiratory obstruction. Long-term survivors have visual loss and often require tracheostomy (McLean et al., 2003). For a discussion of genetic heterogeneity of the subtypes of JEB, see JEB1A (226650). Reviews Has et al. (2020) reviewed the clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors, and natural history of epidermolysis bullosa. [from OMIM]

Additional description

From MedlinePlus Genetics
Laryngo-onycho-cutaneous (LOC) syndrome is a disorder that leads to abnormalities of the voicebox (laryngo-), finger- and toenails (onycho-), and skin (cutaneous). Many of the condition's signs and symptoms are related to the abnormal growth of granulation tissue in different parts of the body. This red, bumpy tissue is normally produced during wound healing and is usually replaced by skin cells as healing continues. However, in people with LOC syndrome, this tissue grows even when there is no major injury.

One of the first symptoms in infants with LOC syndrome is a hoarse cry due to ulcers or overgrowth of granulation tissue in the voicebox (the larynx). Excess granulation tissue can also block the airways, leading to life-threatening breathing problems; as a result many affected individuals do not survive past childhood.

In LOC syndrome, granulation tissue also grows in the eyes, specifically the conjunctiva, which are the moist tissues that line the eyelids and the white part of the eyes. Affected individuals often have impairment or complete loss of vision due to the tissue overgrowth.

Another common feature of LOC syndrome is missing patches of skin (cutaneous erosions). The erosions heal slowly and may become infected. People with LOC syndrome can also have malformed nails and small, abnormal teeth. The hard, white material that forms the protective outer layer of each tooth (enamel) is thin, which contributes to frequent cavities.

LOC syndrome is typically considered a subtype of another skin condition called junctional epidermolysis bullosa, which is characterized by fragile skin that blisters easily. While individuals with junctional epidermolysis bullosa can have some of the features of LOC syndrome, they do not usually have overgrowth of granulation tissue in the conjunctiva.  https://medlineplus.gov/genetics/condition/laryngo-onycho-cutaneous-syndrome

Clinical features

From HPO
Amelogenesis imperfecta
MedGen UID:
240
Concept ID:
C0002452
Congenital Abnormality
A developmental dysplasia of the dental enamel.
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding
Hoarse cry
MedGen UID:
394791
Concept ID:
C2678303
Finding
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Symblepharon
MedGen UID:
509041
Concept ID:
C0152454
Pathologic Function
A partial or complete adhesion of the palpebral conjunctiva of the eyelid to the bulbar conjunctiva of the eyeball.
Corneal pterygium
MedGen UID:
1625284
Concept ID:
C4520843
Disease or Syndrome
Corneal pterygium is an ocular surface disease characterized mainly by a wing-shaped growth of limbal and conjunctival tissue over the adjacent cornea.
Skin ulcer
MedGen UID:
52369
Concept ID:
C0037299
Disease or Syndrome
A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Recurrent loss of toenails and fingernails
MedGen UID:
867184
Concept ID:
C4021542
Finding
Repeated loss, or shedding, of the nails of the fingers and toes.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLaryngo-onycho-cutaneous syndrome
Follow this link to review classifications for Laryngo-onycho-cutaneous syndrome in Orphanet.

Recent clinical studies

Etiology

Phillips PS, Amonoo-Kuofi K, Hore ID, Atherton DJ, Albert DM
Pediatr Dermatol 2006 Jan-Feb;23(1):75-7. doi: 10.1111/j.1525-1470.2006.00176.x. PMID: 16445419
Phillips RJ, Atherton DJ, Gibbs ML, Strobel S, Lake BD
Arch Dis Child 1994 Apr;70(4):319-26. doi: 10.1136/adc.70.4.319. PMID: 8185366Free PMC Article

Diagnosis

Prodinger C, Chottianchaiwat S, Mellerio JE, McGrath JA, Ozoemena L, Liu L, Moore W, Laimer M, Petrof G, Martinez AE
Pediatr Dermatol 2021 Sep;38(5):1094-1101. Epub 2021 Sep 13 doi: 10.1111/pde.14790. PMID: 34514630
Meel R, Wadhwani M
Nepal J Ophthalmol 2019 Jan;11(21):105-107. doi: 10.3126/nepjoph.v11i1.25446. PMID: 31523077
Barzegar M, Asadi-Kani Z, Mozafari N, Vahidnezhad H, Kariminejad A, Toossi P
Int J Dermatol 2015 Oct;54(10):e416-23. Epub 2015 Jul 28 doi: 10.1111/ijd.12804. PMID: 26220012
Cohn HI, Murrell DF
Dermatol Clin 2010 Jan;28(1):89-92. doi: 10.1016/j.det.2009.10.010. PMID: 19945620
Phillips PS, Amonoo-Kuofi K, Hore ID, Atherton DJ, Albert DM
Pediatr Dermatol 2006 Jan-Feb;23(1):75-7. doi: 10.1111/j.1525-1470.2006.00176.x. PMID: 16445419

Therapy

Meel R, Wadhwani M
Nepal J Ophthalmol 2019 Jan;11(21):105-107. doi: 10.3126/nepjoph.v11i1.25446. PMID: 31523077
Romanos GE, Slots J, Javed F
J Oral Sci 2013;55(4):359-62. doi: 10.2334/josnusd.55.359. PMID: 24351925
Phillips PS, Amonoo-Kuofi K, Hore ID, Atherton DJ, Albert DM
Pediatr Dermatol 2006 Jan-Feb;23(1):75-7. doi: 10.1111/j.1525-1470.2006.00176.x. PMID: 16445419

Prognosis

Prodinger C, Chottianchaiwat S, Mellerio JE, McGrath JA, Ozoemena L, Liu L, Moore W, Laimer M, Petrof G, Martinez AE
Pediatr Dermatol 2021 Sep;38(5):1094-1101. Epub 2021 Sep 13 doi: 10.1111/pde.14790. PMID: 34514630
Cohn HI, Murrell DF
Dermatol Clin 2010 Jan;28(1):89-92. doi: 10.1016/j.det.2009.10.010. PMID: 19945620
Phillips PS, Amonoo-Kuofi K, Hore ID, Atherton DJ, Albert DM
Pediatr Dermatol 2006 Jan-Feb;23(1):75-7. doi: 10.1111/j.1525-1470.2006.00176.x. PMID: 16445419
McLean WH, Irvine AD, Hamill KJ, Whittock NV, Coleman-Campbell CM, Mellerio JE, Ashton GS, Dopping-Hepenstal PJ, Eady RA, Jamil T, Phillips R, Shabbir SG, Haroon TS, Khurshid K, Moore JE, Page B, Darling J, Atherton DJ, Van Steensel MA, Munro CS, Smith FJ, McGrath JA
Hum Mol Genet 2003 Sep 15;12(18):2395-409. Epub 2003 Jul 15 doi: 10.1093/hmg/ddg234. PMID: 12915477

Clinical prediction guides

McLean WH, Irvine AD, Hamill KJ, Whittock NV, Coleman-Campbell CM, Mellerio JE, Ashton GS, Dopping-Hepenstal PJ, Eady RA, Jamil T, Phillips R, Shabbir SG, Haroon TS, Khurshid K, Moore JE, Page B, Darling J, Atherton DJ, Van Steensel MA, Munro CS, Smith FJ, McGrath JA
Hum Mol Genet 2003 Sep 15;12(18):2395-409. Epub 2003 Jul 15 doi: 10.1093/hmg/ddg234. PMID: 12915477

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