Details of Disease

General Information of Disease (ID: DISXV4YX)

Disease Name Frontonasal dysplasia
Synonyms median cleft syndrome; frontonasal dysplasia 1; FND1; median cleft face syndrome
Definition
A group of rare bone development disorders characterized by an array of abnormalities affecting the eyes, forehead, and nose, and linked to midfacial dysraphia. The clinical picture is highly variable, but the major findings include hypertelorism, a broad nasal root, a large and bifid nasal tip, and widow's peak. Occasionally, abnormalities can include accessory nasal tags, cleft lip, ocular abnormalities (coloboma, cataract, microphthalmia), conductive hearing loss, basal encephalocele and/or agenesis of the corpus callosum. Intellectual deficit is rare and more likely to occur in cases where hypertelorism is severe or where there is extra-cranial involvement.
Disease Hierarchy
DISYKSRF: Genetic disease
DISHPNVX: Dysplasia
DISXV4YX: Frontonasal dysplasia
Disease Identifiers
MONDO ID
MONDO_0016643
MESH ID
C538065
UMLS CUI
C1876203
MedGen ID
406292
Orphanet ID
250
SNOMED CT ID
86610004

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 9 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
ALX3 OTXZ25PZ Limited Genetic Variation [1]
SIX2 OTYOVGSC Limited Genetic Variation [2]
ALX1 OTZVARA5 Strong Genetic Variation [3]
ALX4 OTNS9A29 Strong Genetic Variation [4]
EFNB1 OT7JJW8P Strong Genetic Variation [5]
HSH2D OTOGB2BR Strong Biomarker [6]
INPP5K OTQFLQKA Strong Biomarker [7]
IRX5 OT05J514 Strong Biomarker [8]
SH2D3A OTVJBSRC Strong Genetic Variation [1]
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⏷ Show the Full List of 9 DOT(s)

References

1 Exome sequencing revealed a novel nonsense variant in ALX3 gene underlying frontorhiny.J Hum Genet. 2018 Jan;63(1):97-100. doi: 10.1038/s10038-017-0358-y. Epub 2017 Nov 16.
2 Crucial and Overlapping Roles of Six1 and Six2 in Craniofacial Development.J Dent Res. 2019 May;98(5):572-579. doi: 10.1177/0022034519835204. Epub 2019 Mar 24.
3 Exome sequencing revealed a novel splice site variant in the ALX1 gene underlying frontonasal dysplasia. Clin Genet. 2017 Mar;91(3):494-498. doi: 10.1111/cge.12822. Epub 2016 Jul 12.
4 Identification of a novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type-2.Am J Med Genet A. 2018 May;176(5):1190-1194. doi: 10.1002/ajmg.a.38655.
5 Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes.Hum Mol Genet. 2013 Apr 15;22(8):1654-62. doi: 10.1093/hmg/ddt015. Epub 2013 Jan 17.
6 Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia. Am J Hum Genet. 2010 May 14;86(5):789-96. doi: 10.1016/j.ajhg.2010.04.002. Epub 2010 May 6.
7 Potocki-Shaffer deletion encompassing ALX4 in a patient with frontonasal dysplasia phenotype.Am J Med Genet A. 2014 Feb;164A(2):346-52. doi: 10.1002/ajmg.a.36140. Epub 2013 Dec 13.
8 Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1. Nat Genet. 2012 May 13;44(6):709-13. doi: 10.1038/ng.2259.