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Frontonasal dysplasia(FND)

MedGen UID:
406292
Concept ID:
C1876203
Congenital Abnormality
Synonyms: FND; Frontonasal dysplasia sequence; Median facial cleft syndrome
SNOMED CT: Frontonasal dysplasia sequence (86610004); Median cleft face syndrome (86610004)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Monarch Initiative: MONDO:0016643
OMIM® Phenotypic series: PS136760
Orphanet: ORPHA250

Definition

The term frontonasal dysplasia was coined by Sedano et al. (1970) to describe a constellation of findings limited to the face and head. The disorder is defined as 2 or more of the following: (1) true ocular hypertelorism; (2) broadening of the nasal root; (3) median facial cleft affecting the nose and/or upper lip and palate; (4) unilateral or bilateral clefting of the alae nasi; (5) lack of formation of the nasal tip; (6) anterior cranium bifidum occultum (see 168500); and (7) a V-shaped or widow's peak frontal hairline (Sedano and Gorlin, 1988). Most reported cases are sporadic, but a few familial cases have been reported. Twigg et al. (2009) characterized frontonasal malformation (FNM) as a 'very heterogeneous group of disorders' and summarized clinical features. Also see acromelic frontonasal dysplasia (AFND; 603671), frontofacionasal dysplasia (FFND; 229400), oculoauriculofrontonasal syndrome (OAFNS; 601452), the acrofrontofacionasal dysostosis syndromes (201180, 239710), and craniofrontonasal syndrome (304110). Genetic Heterogeneity of Frontonasal Dysplasia Frontonasal dysplasia-2 (FND2; 613451) is caused by mutation in the ALX4 gene (605420) on chromosome 11p11. Frontonasal dysplasia-3 (FND3; 613456) is caused by mutation in the ALX1 gene (601527) on chromosome 12q21. [from OMIM]

Additional description

From MedlinePlus Genetics
Frontonasal dysplasia is a condition that results from abnormal development of the head and face before birth. People with frontonasal dysplasia have at least two of the following features: widely spaced eyes (ocular hypertelorism); a broad nose; a slit (cleft) in one or both sides of the nose; no nasal tip; a central cleft involving the nose, upper lip, or roof of the mouth (palate); incomplete formation of the front of the skull with skin covering the head where bone should be (anterior cranium bifidum occultum); or a widow's peak hairline.

Other features of frontonasal dysplasia can include additional facial malformations, absence or malformation of the tissue that connects the left and right halves of the brain (the corpus callosum), and intellectual disability.

There are at least three types of frontonasal dysplasia that are distinguished by their genetic causes and their signs and symptoms. In addition to the features previously described, each type of frontonasal dysplasia is associated with other distinctive features. Individuals with frontonasal dysplasia type 1 typically have abnormalities of the nose, a long area between the nose and upper lip (philtrum), and droopy upper eyelids (ptosis). Individuals with frontonasal dysplasia type 2 can have hair loss (alopecia) and an enlarged opening in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). Males with this form of the condition often have genital abnormalities. Features of frontonasal dysplasia type 3 include eyes that are missing (anophthalmia) or very small (microphthalmia) and low-set ears that are rotated backward. Frontonasal dysplasia type 3 is typically associated with the most severe facial abnormalities, but the severity of the condition varies widely, even among individuals with the same type.

Life expectancy of affected individuals depends on the severity of the malformations and whether or not surgical intervention can improve associated health problems, such as breathing and feeding problems caused by the facial clefts.  https://medlineplus.gov/genetics/condition/frontonasal-dysplasia

Professional guidelines

PubMed

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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
Mallory S, Yap LH, Jones BM, Bingham R
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Recent clinical studies

Etiology

Kim YB, Nam SM, Park ES, Choi CY, Cha HG, Kim JH
Cleft Palate Craniofac J 2022 Oct;59(10):1306-1313. Epub 2021 Aug 17 doi: 10.1177/10556656211036614. PMID: 34402319
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
Mazzola RF, Mazzola IC
J Craniofac Surg 2014 Jan;25(1):26-34. doi: 10.1097/SCS.0b013e3182a2ea94. PMID: 24406554
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Diagnosis

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
Olivero F, Foiadelli T, Luzzi S, Marseglia GL, Savasta S
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Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Therapy

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
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Prognosis

Peled A, Sarig O, Mohamad J, Eskin-Schwartz M, Vodo D, Bochner R, Malchin N, Isakov O, Shomron N, Fainberg G, Bertolini M, Paus R, Sprecher E
Am J Med Genet A 2023 Dec;191(12):2806-2812. Epub 2023 Sep 19 doi: 10.1002/ajmg.a.63408. PMID: 37724761
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de Boutray M, Beziat JL, Yachouh J, Bigorre M, Gleizal A, Captier G
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Chen CP
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Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Clinical prediction guides

Peled A, Sarig O, Mohamad J, Eskin-Schwartz M, Vodo D, Bochner R, Malchin N, Isakov O, Shomron N, Fainberg G, Bertolini M, Paus R, Sprecher E
Am J Med Genet A 2023 Dec;191(12):2806-2812. Epub 2023 Sep 19 doi: 10.1002/ajmg.a.63408. PMID: 37724761
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
Mazzola RF, Mazzola IC
J Craniofac Surg 2014 Jan;25(1):26-34. doi: 10.1097/SCS.0b013e3182a2ea94. PMID: 24406554
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
Kapusta L, Brunner HG, Hamel BC
Eur J Pediatr 1992 Nov;151(11):837-41. doi: 10.1007/BF01957936. PMID: 1468459

Recent systematic reviews

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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