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Cleft lip/palate-intestinal malrotation-cardiopathy syndrome

MedGen UID:
444135
Concept ID:
C2931750
Disease or Syndrome
Synonyms: Cleft lip, cleft palate, characteristic facies, intestinal malrotation, and lethal congenital heart disease; Cleft lip/palate with characteristic facies, intestinal malrotation, and lethal congenital heart disease; McPherson Clemens syndrome
SNOMED CT: McPherson Clemens syndrome (719456001); Cleft lip and cleft palate with intestinal malrotation and cardiopathy syndrome (719456001)
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:0011008
OMIM®: 601165
Orphanet: ORPHA2001

Definition

A multiple congenital anomaly syndrome described in 5 patients to date. Characteristics include flat face, hypertelorism, flat occiput, upward slanting palpebral fissures, cleft palate, micrognathia, short neck, and severe congenital heart defects, which were lethal in 3 of the 5 patients. Malrotation of the intestine, bilateral clinodactyly, bilobed tongue, short fourth metatarsals and bifid thumbs were reported in individual cases. There have been no further descriptions in the literature since 1997. [from SNOMEDCT_US]

Clinical features

From HPO
Broad palm
MedGen UID:
75535
Concept ID:
C0264142
Congenital Abnormality
For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length.
Short palm
MedGen UID:
334684
Concept ID:
C1843108
Finding
Short palm.
Abnormal hand morphology
MedGen UID:
870655
Concept ID:
C4025109
Anatomical Abnormality
Any structural anomaly of the hand.
Partial duplication of thumb phalanx
MedGen UID:
909031
Concept ID:
C4082168
Anatomical Abnormality
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the thumb. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
Abnormality of cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Congenital Abnormality
Any structural anomaly of the heart and great vessels.
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
Visceromegaly
MedGen UID:
22659
Concept ID:
C0042782
Pathologic Function
Abnormal increased size of the viscera of the abdomen.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Pancreatic islet-cell hyperplasia
MedGen UID:
108598
Concept ID:
C0597167
Finding
Hyperplasia of the islets of Langerhans, i.e., of the regions of the pancreas that contain its endocrine cells.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Cleft upper lip
MedGen UID:
40327
Concept ID:
C0008924
Congenital Abnormality
A gap in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Abnormality of the tongue
MedGen UID:
451075
Concept ID:
C0878638
Finding
Any abnormality of the tongue.
Bilateral cleft lip and palate
MedGen UID:
853256
Concept ID:
C1398522
Congenital Abnormality
Cleft lip and cleft palate affecting both sides of the face.
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
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

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCleft lip/palate-intestinal malrotation-cardiopathy syndrome
Follow this link to review classifications for Cleft lip/palate-intestinal malrotation-cardiopathy syndrome in Orphanet.

Professional guidelines

PubMed

Batista KB, Thiruvenkatachari B, Harrison JE, O'Brien KD
Cochrane Database Syst Rev 2018 Mar 13;3(3):CD003452. doi: 10.1002/14651858.CD003452.pub4. PMID: 29534303Free PMC Article
Stamou MI, Georgopoulos NA
Metabolism 2018 Sep;86:124-134. Epub 2017 Nov 3 doi: 10.1016/j.metabol.2017.10.012. PMID: 29108899Free PMC Article
Lee AS, Gibbon FE
Cochrane Database Syst Rev 2015 Mar 25;2015(3):CD009383. doi: 10.1002/14651858.CD009383.pub2. PMID: 25805060Free PMC Article

Recent clinical studies

Etiology

Dardani C, Howe LJ, Mukhopadhyay N, Stergiakouli E, Wren Y, Humphries K, Davies A, Ho K, Weinberg SM, Marazita ML, Mangold E, Ludwig KU, Relton CL, Davey Smith G, Lewis SJ, Sandy J, Davies NM, Sharp GC
Int J Epidemiol 2020 Aug 1;49(4):1282-1293. doi: 10.1093/ije/dyaa047. PMID: 32373937Free PMC Article
Johnson MM
Radiol Technol 2019 Jul;90(6):581-596. PMID: 31270258
Gatti GL, Freda N, Giacomina A, Montemagni M, Sisti A
J Craniofac Surg 2017 Nov;28(8):1918-1924. doi: 10.1097/SCS.0000000000003820. PMID: 29088690
Setó-Salvia N, Stanier P
Eur J Med Genet 2014 Aug;57(8):381-93. Epub 2014 Apr 21 doi: 10.1016/j.ejmg.2014.04.003. PMID: 24768816
Dixon MJ, Marazita ML, Beaty TH, Murray JC
Nat Rev Genet 2011 Mar;12(3):167-78. doi: 10.1038/nrg2933. PMID: 21331089Free PMC Article

Diagnosis

Pach J, Regulski PA, Tomczyk J, Strużycka I
Adv Clin Exp Med 2022 Dec;31(12):1385-1389. doi: 10.17219/acem/152120. PMID: 36000881
Johnson MM
Radiol Technol 2019 Jul;90(6):581-596. PMID: 31270258
Gatti GL, Freda N, Giacomina A, Montemagni M, Sisti A
J Craniofac Surg 2017 Nov;28(8):1918-1924. doi: 10.1097/SCS.0000000000003820. PMID: 29088690
Lewis CW, Jacob LS, Lehmann CU; SECTION ON ORAL HEALTH
Pediatrics 2017 May;139(5) doi: 10.1542/peds.2017-0628. PMID: 28557774
Digilio MC, Dallapiccola B
Orphanet J Rare Dis 2010 Sep 29;5:25. doi: 10.1186/1750-1172-5-25. PMID: 20920258Free PMC Article

Therapy

Dardani C, Howe LJ, Mukhopadhyay N, Stergiakouli E, Wren Y, Humphries K, Davies A, Ho K, Weinberg SM, Marazita ML, Mangold E, Ludwig KU, Relton CL, Davey Smith G, Lewis SJ, Sandy J, Davies NM, Sharp GC
Int J Epidemiol 2020 Aug 1;49(4):1282-1293. doi: 10.1093/ije/dyaa047. PMID: 32373937Free PMC Article
Kloukos D, Fudalej P, Sequeira-Byron P, Katsaros C
Cochrane Database Syst Rev 2018 Aug 10;8(8):CD010403. doi: 10.1002/14651858.CD010403.pub3. PMID: 30095853Free PMC Article
Batista KB, Thiruvenkatachari B, Harrison JE, O'Brien KD
Cochrane Database Syst Rev 2018 Mar 13;3(3):CD003452. doi: 10.1002/14651858.CD003452.pub4. PMID: 29534303Free PMC Article
Gatti GL, Freda N, Giacomina A, Montemagni M, Sisti A
J Craniofac Surg 2017 Nov;28(8):1918-1924. doi: 10.1097/SCS.0000000000003820. PMID: 29088690
Lee AS, Gibbon FE
Cochrane Database Syst Rev 2015 Mar 25;2015(3):CD009383. doi: 10.1002/14651858.CD009383.pub2. PMID: 25805060Free PMC Article

Prognosis

Pach J, Regulski PA, Tomczyk J, Strużycka I
Adv Clin Exp Med 2022 Dec;31(12):1385-1389. doi: 10.17219/acem/152120. PMID: 36000881
Kylat RI
Acta Paediatr 2022 May;111(5):948-951. Epub 2022 Jan 31 doi: 10.1111/apa.16260. PMID: 35044009
Siddique AW, Ahmed Z, Haider A, Khalid H, Karim T
J Ayub Med Coll Abbottabad 2019 Apr-Jun;31(2):290-292. PMID: 31094135
Batista KB, Thiruvenkatachari B, Harrison JE, O'Brien KD
Cochrane Database Syst Rev 2018 Mar 13;3(3):CD003452. doi: 10.1002/14651858.CD003452.pub4. PMID: 29534303Free PMC Article
Digilio MC, Dallapiccola B
Orphanet J Rare Dis 2010 Sep 29;5:25. doi: 10.1186/1750-1172-5-25. PMID: 20920258Free PMC Article

Clinical prediction guides

Novelli F, Ganini C, Melino G, Nucci C, Han Y, Shi Y, Wang Y, Candi E
Biochem Biophys Res Commun 2022 Jun 25;610:15-22. Epub 2022 Apr 9 doi: 10.1016/j.bbrc.2022.04.022. PMID: 35430447
Marzouk T, Alves IL, Wong CL, DeLucia L, McKinney CM, Pendleton C, Howe BJ, Marazita ML, Peter TK, Kopycka-Kedzierawski DT, Morrison CS, Malmstrom H, Wang H, Shope ET
JDR Clin Trans Res 2021 Oct;6(4):368-381. Epub 2020 Oct 8 doi: 10.1177/2380084420964795. PMID: 33030085Free PMC Article
Dardani C, Howe LJ, Mukhopadhyay N, Stergiakouli E, Wren Y, Humphries K, Davies A, Ho K, Weinberg SM, Marazita ML, Mangold E, Ludwig KU, Relton CL, Davey Smith G, Lewis SJ, Sandy J, Davies NM, Sharp GC
Int J Epidemiol 2020 Aug 1;49(4):1282-1293. doi: 10.1093/ije/dyaa047. PMID: 32373937Free PMC Article
Gatti GL, Freda N, Giacomina A, Montemagni M, Sisti A
J Craniofac Surg 2017 Nov;28(8):1918-1924. doi: 10.1097/SCS.0000000000003820. PMID: 29088690
Stevens CA, Wilroy RS Jr
J Med Genet 1988 Aug;25(8):536-42. doi: 10.1136/jmg.25.8.536. PMID: 3050099Free PMC Article

Recent systematic reviews

Marzouk T, Alves IL, Wong CL, DeLucia L, McKinney CM, Pendleton C, Howe BJ, Marazita ML, Peter TK, Kopycka-Kedzierawski DT, Morrison CS, Malmstrom H, Wang H, Shope ET
JDR Clin Trans Res 2021 Oct;6(4):368-381. Epub 2020 Oct 8 doi: 10.1177/2380084420964795. PMID: 33030085Free PMC Article
Kloukos D, Fudalej P, Sequeira-Byron P, Katsaros C
Cochrane Database Syst Rev 2018 Aug 10;8(8):CD010403. doi: 10.1002/14651858.CD010403.pub3. PMID: 30095853Free PMC Article
Batista KB, Thiruvenkatachari B, Harrison JE, O'Brien KD
Cochrane Database Syst Rev 2018 Mar 13;3(3):CD003452. doi: 10.1002/14651858.CD003452.pub4. PMID: 29534303Free PMC Article
Duarte GA, Ramos RB, Cardoso MC
Braz J Otorhinolaryngol 2016 Sep-Oct;82(5):602-9. Epub 2016 Mar 2 doi: 10.1016/j.bjorl.2015.10.020. PMID: 26997574Free PMC Article
Lee AS, Gibbon FE
Cochrane Database Syst Rev 2015 Mar 25;2015(3):CD009383. doi: 10.1002/14651858.CD009383.pub2. PMID: 25805060Free PMC Article

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