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Crouzon syndrome-acanthosis nigricans syndrome(CAN)

MedGen UID:
394201
Concept ID:
C2677099
Disease or Syndrome
Synonyms: Crouzon syndrome with acanthosis nigricans; CROUZONODERMOSKELETAL SYNDROME
SNOMED CT: Crouzon syndrome with acanthosis nigricans (702361006); Crouzonodermoskeletal syndrome (702361006)
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.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): FGFR3 (4p16.3)
 
Monarch Initiative: MONDO:0012833
OMIM®: 612247
Orphanet: ORPHA93262

Definition

Crouzon syndrome with acanthosis nigricans is considered to be a distinct disorder from classic Crouzon syndrome (123500), which is caused by mutation in the FGFR2 gene (176943). Cohen (1999) argued that this condition is separate from Crouzon syndrome for 2 main reasons: it is caused by a highly specific mutation of the FGFR3 gene, whereas multiple different FGFR2 mutations result in Crouzon syndrome, and the phenotypes are different. [from OMIM]

Additional description

From MedlinePlus Genetics
Crouzon syndrome with acanthosis nigricans is a disorder characterized by the premature joining of certain bones of the skull (craniosynostosis) during development and a skin condition called acanthosis nigricans.

The signs and symptoms of Crouzon syndrome with acanthosis nigricans overlap with those of a similar condition called Crouzon syndrome. Both conditions involve premature fusion of the skull bones, which affects the shape of the head and face. Other common features of both conditions include wide-set, bulging eyes due to shallow eye sockets; eyes that do not point in the same direction (strabismus); a small, beaked nose; and a flat or sunken appearance of the middle of the face (midface hypoplasia). Less common features that can occur in either disorder include an opening in the roof of the mouth (cleft palate), dental problems, or hearing loss. People with Crouzon syndrome or Crouzon syndrome with acanthosis nigricans usually have normal intelligence.

Crouzon syndrome with acanthosis nigricans is distinguished from Crouzon syndrome by several features, including skin abnormalities. Acanthosis nigricans is a skin condition characterized by thick, dark, velvety skin in body folds and creases, including the neck and underarms. People with Crouzon syndrome with acanthosis nigricans may also have other skin abnormalities; for example, scars in the thick, dark areas of skin are flat and pale. These scars are usually from surgical procedures that are commonly needed in affected individuals. Additionally, in some people with the condition, one or both nasal passages are narrowed (choanal stenosis) or completely blocked (choanal atresia), which can cause difficulty breathing. A buildup of fluid in the brain (hydrocephalus) can also occur. Nasal passage abnormalities and hydrocephalus are rare in Crouzon syndrome. Less common features of Crouzon syndrome with acanthosis nigricans include subtle changes in the bones of the spine (vertebrae), abnormalities of the finger bones, and noncancerous growths in the jaw called cementomas.  https://medlineplus.gov/genetics/condition/crouzon-syndrome-with-acanthosis-nigricans

Clinical features

From HPO
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Choanal atresia
MedGen UID:
3395
Concept ID:
C0008297
Congenital Abnormality
Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Melanocytic nevus
MedGen UID:
14364
Concept ID:
C0027962
Neoplastic Process
A oval and round, colored (usually medium-to dark brown, reddish brown, or flesh colored) lesion. Typically, a melanocytic nevus is less than 6 mm in diameter, but may be much smaller or larger.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

Follow this link to review classifications for Crouzon syndrome-acanthosis nigricans syndrome in Orphanet.

Professional guidelines

PubMed

Lam AS, Liu CC, Deutsch GH, Rivera J, Perkins JA, Holmes G, Jabs EW, Cunningham ML, Dahl JP
Laryngoscope 2021 Apr;131(4):E1349-E1356. Epub 2020 Sep 4 doi: 10.1002/lary.29060. PMID: 32886384Free PMC Article

Recent clinical studies

Etiology

Tripathi T, Srivastava D, Bhutiani N, Rai P
J Orthod 2022 Mar;49(1):71-78. Epub 2021 Jun 8 doi: 10.1177/14653125211019412. PMID: 34100307
de Planque CA, Wall SA, Dalton L, Paternoster G, Arnaud É, van Veelen MC, Versnel SL, Johnson D, Jayamohan J, Mathijssen IMJ
J Neurosurg Pediatr 2021 Oct 1;28(4):425-431. Epub 2021 Aug 13 doi: 10.3171/2021.2.PEDS20933. PMID: 34388723
Lam AS, Liu CC, Deutsch GH, Rivera J, Perkins JA, Holmes G, Jabs EW, Cunningham ML, Dahl JP
Laryngoscope 2021 Apr;131(4):E1349-E1356. Epub 2020 Sep 4 doi: 10.1002/lary.29060. PMID: 32886384Free PMC Article
Mulliken JB, Steinberger D, Kunze S, Müller U
Plast Reconstr Surg 1999 Nov;104(6):1603-15. doi: 10.1097/00006534-199911000-00001. PMID: 10541159
Breitbart AS, Eaton C, McCarthy JG
Ann Plast Surg 1989 Apr;22(4):310-5. doi: 10.1097/00000637-198904000-00005. PMID: 2650599

Diagnosis

Olshinka A, Tal D, Gillman L, Ad-El D, Kalish E, Kropach N, Yaacobi DS, Kornreich L, Staffenberg DA
J Craniofac Surg 2021 Jan-Feb 01;32(1):310-312. doi: 10.1097/SCS.0000000000007095. PMID: 33156176
Sargar KM, Singh AK, Kao SC
Radiographics 2017 Oct;37(6):1813-1830. doi: 10.1148/rg.2017170017. PMID: 29019756
Agochukwu NB, Solomon BD, Muenke M
Int J Pediatr Otorhinolaryngol 2014 Dec;78(12):2037-47. Epub 2014 Sep 28 doi: 10.1016/j.ijporl.2014.09.019. PMID: 25441602
Jeftha A, Stephen L, Morkel JA, Beighton P
J Clin Pediatr Dent 2004 Winter;28(2):173-6. doi: 10.17796/jcpd.28.2.72m01l5g50448548. PMID: 14969379
Mulliken JB, Steinberger D, Kunze S, Müller U
Plast Reconstr Surg 1999 Nov;104(6):1603-15. doi: 10.1097/00006534-199911000-00001. PMID: 10541159

Therapy

Alatzoglou KS, Hindmarsh PC, Brain C, Torpiano J, Dattani MT
J Clin Endocrinol Metab 2009 Oct;94(10):3959-63. Epub 2009 Jul 21 doi: 10.1210/jc.2009-0322. PMID: 19622626

Prognosis

Tripathi T, Srivastava D, Bhutiani N, Rai P
J Orthod 2022 Mar;49(1):71-78. Epub 2021 Jun 8 doi: 10.1177/14653125211019412. PMID: 34100307
de Planque CA, Wall SA, Dalton L, Paternoster G, Arnaud É, van Veelen MC, Versnel SL, Johnson D, Jayamohan J, Mathijssen IMJ
J Neurosurg Pediatr 2021 Oct 1;28(4):425-431. Epub 2021 Aug 13 doi: 10.3171/2021.2.PEDS20933. PMID: 34388723
Wenger TL, Bhoj EJ, Wetmore RF, Mennuti MT, Bartlett SP, Mollen TJ, McDonald-McGinn DM, Zackai EH
Am J Med Genet A 2015 Apr;167A(4):852-7. Epub 2015 Feb 23 doi: 10.1002/ajmg.a.36985. PMID: 25706251
Barroso E, Pérez-Carrizosa V, García-Recuero I, Glucksman MJ, Wilkie AO, García-Minaur S, Heath KE
Am J Med Genet A 2011 Dec;155A(12):3050-3. Epub 2011 Oct 28 doi: 10.1002/ajmg.a.34199. PMID: 22038757
Chen LI, Webster MK, Meyer AN, Donoghue DJ
J Cell Biol 1997 May 5;137(3):619-31. doi: 10.1083/jcb.137.3.619. PMID: 9151669Free PMC Article

Clinical prediction guides

Lam AS, Liu CC, Deutsch GH, Rivera J, Perkins JA, Holmes G, Jabs EW, Cunningham ML, Dahl JP
Laryngoscope 2021 Apr;131(4):E1349-E1356. Epub 2020 Sep 4 doi: 10.1002/lary.29060. PMID: 32886384Free PMC Article
Mir A, Wu T, Orlow SJ
JAMA Dermatol 2013 Jun;149(6):737-41. doi: 10.1001/jamadermatol.2013.3019. PMID: 23571469
Jeftha A, Stephen L, Morkel JA, Beighton P
J Clin Pediatr Dent 2004 Winter;28(2):173-6. doi: 10.17796/jcpd.28.2.72m01l5g50448548. PMID: 14969379
Vajo Z, Francomano CA, Wilkin DJ
Endocr Rev 2000 Feb;21(1):23-39. doi: 10.1210/edrv.21.1.0387. PMID: 10696568
Mulliken JB, Steinberger D, Kunze S, Müller U
Plast Reconstr Surg 1999 Nov;104(6):1603-15. doi: 10.1097/00006534-199911000-00001. PMID: 10541159

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