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Carpenter syndrome

MedGen UID:
226897
Concept ID:
C1275078
Disease or Syndrome
Synonyms: ACPS II; Acrocephalopolysyndactyly Type II; Carpenter Syndrome
SNOMED CT: Acrocephalopolysyndactyly type II (403767009); Carpenter syndrome (403767009); Acrocephalopolysyndactyly type 2 (403767009)
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).
 
Monarch Initiative: MONDO:0019012
OMIM®: 201000; 606144
OMIM® Phenotypic series: PS201000
Orphanet: ORPHA65759

Definition

Carpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems.

Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.

Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.

People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability.

Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism).

The signs and symptoms of Carpenter syndrome are similar to another genetic condition called Greig cephalopolysyndactyly syndrome. The overlapping features, which include craniosynostosis, polydactyly, and heart abnormalities, can cause these two conditions to be misdiagnosed; genetic testing is often required for an accurate diagnosis.

A few people with Carpenter syndrome have organs or tissues within their chest and abdomen that are in mirror-image reversed positions. This abnormal placement may affect several internal organs (situs inversus); just the heart (dextrocardia), placing the heart on the right side of the body instead of on the left; or only the major (great) arteries of the heart, altering blood flow.

The signs and symptoms of this disorder vary considerably, even within the same family. The life expectancy for individuals with Carpenter syndrome is shortened but extremely variable. [from MedlinePlus Genetics]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCarpenter syndrome
Follow this link to review classifications for Carpenter syndrome in Orphanet.

Professional guidelines

PubMed

Rubio EI, Blask A, Bulas DI
Pediatr Radiol 2016 May;46(5):709-18. Epub 2016 Feb 25 doi: 10.1007/s00247-016-3550-x. PMID: 26914936

Recent clinical studies

Etiology

Odegaard KE, Gallegos G, Koul S, Schaal VL, Vellichirammal NN, Guda C, Dutoit AP, Lisco SJ, Yelamanchili SV, Pendyala G
Cells 2022 May 25;11(11) doi: 10.3390/cells11111740. PMID: 35681434Free PMC Article
Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L
Hormones (Athens) 2013 Jan-Mar;12(1):39-45. doi: 10.1007/BF03401285. PMID: 23624130
Jenkins D, Baynam G, De Catte L, Elcioglu N, Gabbett MT, Hudgins L, Hurst JA, Jehee FS, Oley C, Wilkie AO
Hum Mutat 2011 Apr;32(4):E2069-78. Epub 2011 Feb 8 doi: 10.1002/humu.21457. PMID: 21412941Free PMC Article
Hidestrand P, Vasconez H, Cottrill C
J Craniofac Surg 2009 Jan;20(1):254-6. doi: 10.1097/SCS.0b013e318184357a. PMID: 19165041
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article

Diagnosis

Khairat R, Elhossini R, Sobreira N, Wohler E, Otaify G, Mohamed AM, Abdel Raouf ER, Sayed I, Aglan M, Ismail S, Temtamy SA
Eur J Med Genet 2022 Jan;65(1):104377. Epub 2021 Nov 5 doi: 10.1016/j.ejmg.2021.104377. PMID: 34748996
Kadakia S, Helman SN, Healy NJ, Saman M, Wood-Smith D
J Craniofac Surg 2014 Sep;25(5):1653-7. doi: 10.1097/SCS.0000000000001121. PMID: 25162549
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article
Amor DJ, Savarirayan R, Schneider AS, Bankier A
Am J Med Genet 2000 Jun 5;92(4):273-7. doi: 10.1002/(sici)1096-8628(20000605)92:4<273::aid-ajmg10>3.0.co;2-t. PMID: 10842295
Cohen MM Jr
Am J Med Genet Suppl 1988;4:99-148. doi: 10.1002/ajmg.1320310514. PMID: 3144990

Therapy

Mircevsk V, Zogovska E, Chaparoski A, Micunovic M, Filipce V, Mirchevski MM, Kostov M, Мicunovic L
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2017 Mar 1;38(1):35-40. doi: 10.1515/prilozi-2017-0004. PMID: 28593893
Zanzottera C, Milani D, Alfei E, Rizzo A, D'Arrigo S, Esposito S, Pantaleoni C
Am J Med Genet A 2017 May;173(5):1358-1363. Epub 2017 Mar 27 doi: 10.1002/ajmg.a.38155. PMID: 28345801

Prognosis

Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L
Hormones (Athens) 2013 Jan-Mar;12(1):39-45. doi: 10.1007/BF03401285. PMID: 23624130
Ramos JM, Davis GJ, Hunsaker JC 3rd, Balko MG
Forensic Sci Med Pathol 2009 Dec;5(4):313-7. Epub 2009 Nov 19 doi: 10.1007/s12024-009-9128-2. PMID: 19924577
Hidestrand P, Vasconez H, Cottrill C
J Craniofac Surg 2009 Jan;20(1):254-6. doi: 10.1097/SCS.0b013e318184357a. PMID: 19165041
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article
Higurashi M, Oda M, Iijima K, Iijima S, Takeshita T, Watanabe N, Yoneyama K
Brain Dev 1990;12(6):770-3. doi: 10.1016/s0387-7604(12)80004-0. PMID: 2092586

Clinical prediction guides

Chen S, Venkatesan A, Lin YQ, Xie J, Neely G, Banerjee S, Bhat MA
J Neurosci 2022 Sep 14;42(37):7016-7030. Epub 2022 Aug 9 doi: 10.1523/JNEUROSCI.0442-22.2022. PMID: 35944997Free PMC Article
Mircevsk V, Zogovska E, Chaparoski A, Micunovic M, Filipce V, Mirchevski MM, Kostov M, Мicunovic L
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2017 Mar 1;38(1):35-40. doi: 10.1515/prilozi-2017-0004. PMID: 28593893
Haye D, Collet C, Sembely-Taveau C, Haddad G, Denis C, Soulé N, Suc AL, Listrat A, Toutain A
Am J Med Genet A 2014 Nov;164A(11):2926-30. Epub 2014 Aug 28 doi: 10.1002/ajmg.a.36726. PMID: 25168863
Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L
Hormones (Athens) 2013 Jan-Mar;12(1):39-45. doi: 10.1007/BF03401285. PMID: 23624130
Jenkins D, Baynam G, De Catte L, Elcioglu N, Gabbett MT, Hudgins L, Hurst JA, Jehee FS, Oley C, Wilkie AO
Hum Mutat 2011 Apr;32(4):E2069-78. Epub 2011 Feb 8 doi: 10.1002/humu.21457. PMID: 21412941Free PMC Article

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