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Six2-related frontonasal dysplasia

MedGen UID:
1798907
•Concept ID:
C5567484
•
Disease or Syndrome
Synonyms: SIX homeobox 2-related frontonasal dysplasia; SIX2-related FND; SIX2-related frontonasal dysplasia; six2-related frontonasal dysplasia
SNOMED CT: SIX2-related frontonasal dysplasia (1172632008); SIX homeobox 2-related frontonasal dysplasia (1172632008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Monarch Initiative: MONDO:0044628
Orphanet: ORPHA488437

Definition

A rare frontonasal dysplasia with characteristics of a craniofacial phenotype comprising frontal bossing with high anterior hairline, ptosis, hypertelorism, epicanthus inversus, flat nasal bridge and broad nasal tip. Large anterior fontanel, sagittal synostosis, and cranial base anomalies have also been described. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSix2-related frontonasal dysplasia

Professional guidelines

PubMed

Toward clinical and molecular dissection of frontonasal dysplasia with facial skin polyps: From Pai syndrome to differential diagnosis through a series of 27 patients.
Lehalle D, Bruel AL, Vitobello A, Denommé-Pichon AS, Duffourd Y, Assoum M, Amiel J, Baujat G, Bessieres B, Bigoni S, Burglen L, Captier G, Dard R, Edery P, Fortunato F, Geneviève D, Goldenberg A, Guibaud L, Héron D, Holder-Espinasse M, Lederer D, Lopez Grondona F, Grotto S, Marlin S, Nadeau G, Picard A, Rossi M, Roume J, Sanlaville D, Saugier-Veber P, Triau S, Valenzuela Palafoll MI, Vanlerberghe C, Van Maldergem L, Vezain M, Vincent-Delorme C, Zivi E, Thevenon J, Vabres P, Thauvin-Robinet C, Callier P, Faivre L
Am J Med Genet A 2022 Jul;188(7):2036-2047. Epub 2022 Apr 21 doi: 10.1002/ajmg.a.62739. PMID: 35445792
ALX-Related Frontonasal Dysplasias: Clinical Characteristics and Surgical Management.
Vargel I, Canter HI, Kucukguven A, Aydin A, Ozgur F
Cleft Palate Craniofac J 2022 May;59(5):637-643. Epub 2021 Jun 8 doi: 10.1177/10556656211019621. PMID: 34098755
Anaesthetic management in facial bipartition surgery: the experience of one centre.
Mallory S, Yap LH, Jones BM, Bingham R
Anaesthesia 2004 Jan;59(1):44-51. doi: 10.1111/j.1365-2044.2004.03529.x. PMID: 14687098

Recent clinical studies

Etiology

ALX-Related Frontonasal Dysplasias: Clinical Characteristics and Surgical Management.
Vargel I, Canter HI, Kucukguven A, Aydin A, Ozgur F
Cleft Palate Craniofac J 2022 May;59(5):637-643. Epub 2021 Jun 8 doi: 10.1177/10556656211019621. PMID: 34098755
Median cleft of the upper lip: A new classification to guide treatment decisions.
de Boutray M, Beziat JL, Yachouh J, Bigorre M, Gleizal A, Captier G
J Craniomaxillofac Surg 2016 Jun;44(6):664-71. Epub 2016 Mar 2 doi: 10.1016/j.jcms.2016.02.012. PMID: 27075944
A new frontonasal dysplasia syndrome associated with deletion of the SIX2 gene.
Hufnagel RB, Zimmerman SL, Krueger LA, Bender PL, Ahmed ZM, Saal HM
Am J Med Genet A 2016 Feb;170A(2):487-491. Epub 2015 Nov 18 doi: 10.1002/ajmg.a.37441. PMID: 26581443Free PMC Article
Facial clefts and facial dysplasia: revisiting the classification.
Mazzola RF, Mazzola IC
J Craniofac Surg 2014 Jan;25(1):26-34. doi: 10.1097/SCS.0b013e3182a2ea94. PMID: 24406554
Craniofrontonasal dysplasia.
Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Diagnosis

ALX-Related Frontonasal Dysplasias: Clinical Characteristics and Surgical Management.
Vargel I, Canter HI, Kucukguven A, Aydin A, Ozgur F
Cleft Palate Craniofac J 2022 May;59(5):637-643. Epub 2021 Jun 8 doi: 10.1177/10556656211019621. PMID: 34098755
Pai syndrome: a review.
Olivero F, Foiadelli T, Luzzi S, Marseglia GL, Savasta S
Childs Nerv Syst 2020 Nov;36(11):2635-2640. Epub 2020 Jul 10 doi: 10.1007/s00381-020-04788-z. PMID: 32651596Free PMC Article
Facial clefts and facial dysplasia: revisiting the classification.
Mazzola RF, Mazzola IC
J Craniofac Surg 2014 Jan;25(1):26-34. doi: 10.1097/SCS.0b013e3182a2ea94. PMID: 24406554
Frontonasal dysplasia: analysis of 21 cases and literature review.
Guion-Almeida ML, Richieri-Costa A, Saavedra D, Cohen MM Jr
Int J Oral Maxillofac Surg 1996 Apr;25(2):91-7. doi: 10.1016/s0901-5027(96)80048-8. PMID: 8727576
Craniofrontonasal dysplasia.
Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Therapy

Surgical Correction of a Bifid Nose Deformity with a Split M-Shaped Flap.
Wang Y, Yu B, Dai C, Wei J
Facial Plast Surg Aesthet Med 2023 May-Jun;25(3):238-243. Epub 2022 Jul 19 doi: 10.1089/fpsam.2022.0077. PMID: 35856821
Exome sequencing revealed a novel nonsense variant in ALX3 gene underlying frontorhiny.
Ullah A, Umair M, E-Kalsoom U, Shahzad S, Basit S, Ahmad W
J Hum Genet 2018 Jan;63(1):97-100. Epub 2017 Nov 16 doi: 10.1038/s10038-017-0358-y. PMID: 29215096
Ocular Morbidity in the Correction of Orbital Hypertelorism and Dystopia: A 15-Year Experience.
Glass GE, Hon KAV, Schweibert K, Bowman R, Jones BM, Dunaway DJ, Britto JA
Plast Reconstr Surg 2017 Apr;139(4):967-975. doi: 10.1097/PRS.0000000000003178. PMID: 28350678
A long-term evaluation of 150 costochondral nasal grafts.
Chummun S, McLean NR, Anderson PJ, David DJ
J Plast Reconstr Aesthet Surg 2013 Nov;66(11):1477-81. Epub 2013 Jul 30 doi: 10.1016/j.bjps.2013.07.004. PMID: 23910911
Salvage of calvarial bone graft using acellular dermal matrix in nasal reconstruction and secondary rhinoplasty for frontonasal dysplasia.
Lenyoun EH, Lampert JA, Xipoleas GD, Taub PJ
J Craniofac Surg 2011 Jul;22(4):1378-82. doi: 10.1097/SCS.0b013e31821cc26d. PMID: 21772175

Prognosis

Surgical Strategies for Soft Tissue Management in Hypertelorbitism.
Raposo-Amaral CE, Denadai R, Ghizoni E, Raposo-Amaral CA
Ann Plast Surg 2017 Apr;78(4):421-427. doi: 10.1097/SAP.0000000000000915. PMID: 27740959
Median cleft of the upper lip: A new classification to guide treatment decisions.
de Boutray M, Beziat JL, Yachouh J, Bigorre M, Gleizal A, Captier G
J Craniomaxillofac Surg 2016 Jun;44(6):664-71. Epub 2016 Mar 2 doi: 10.1016/j.jcms.2016.02.012. PMID: 27075944
Salvage of calvarial bone graft using acellular dermal matrix in nasal reconstruction and secondary rhinoplasty for frontonasal dysplasia.
Lenyoun EH, Lampert JA, Xipoleas GD, Taub PJ
J Craniofac Surg 2011 Jul;22(4):1378-82. doi: 10.1097/SCS.0b013e31821cc26d. PMID: 21772175
Syndromes, disorders and maternal risk factors associated with neural tube defects (V).
Chen CP
Taiwan J Obstet Gynecol 2008 Sep;47(3):259-66. doi: 10.1016/S1028-4559(08)60122-9. PMID: 18935987
Craniofrontonasal dysplasia.
Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Clinical prediction guides

Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients.
Lehalle D, Altunoglu U, Bruel AL, Arnaud E, Blanchet P, Choi JW, Désir J, Kiliç E, Lederer D, Pinson L, Thauvin-Robinet C, Singer A, Thevenon J, Callier P, Kayserili H, Faivre L
Am J Med Genet A 2017 Dec;173(12):3136-3142. doi: 10.1002/ajmg.a.38490. PMID: 29136349
Tooth Abnormalities and Occlusal Disorders in Individuals With Frontonasal Dysplasia.
Dainezi VB, Neves LTD, da Silva Dalben G, Gomide MR
Cleft Palate Craniofac J 2017 May;54(3):304-308. Epub 2016 Feb 16 doi: 10.1597/15-286. PMID: 26882026
Facial clefts and facial dysplasia: revisiting the classification.
Mazzola RF, Mazzola IC
J Craniofac Surg 2014 Jan;25(1):26-34. doi: 10.1097/SCS.0b013e3182a2ea94. PMID: 24406554
Frontonasal dysplasia: clinical evaluation on audiological and brainstem electrophysiological profiles.
Antoneli MZ, Giacheti CM, Genaro KF, Zorzetto NL, Richieri-Costa A
Braz J Otorhinolaryngol 2011 Sep-Oct;77(5):611-5. doi: 10.1590/s1808-86942011000500013. PMID: 22030970Free PMC Article
Craniofrontonasal dysplasia.
Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Recent systematic reviews

Median cleft of the upper lip: A new classification to guide treatment decisions.
de Boutray M, Beziat JL, Yachouh J, Bigorre M, Gleizal A, Captier G
J Craniomaxillofac Surg 2016 Jun;44(6):664-71. Epub 2016 Mar 2 doi: 10.1016/j.jcms.2016.02.012. PMID: 27075944

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