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Blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome

MedGen UID:
347880
Concept ID:
C1859432
Disease or Syndrome
Synonym: Blepharophimosis with ptosis, syndactyly, and short stature
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:0008875
OMIM®: 210745
Orphanet: ORPHA2057

Definition

A rare syndrome characterised by the association of blepharophimosis and ptosis, V-esotropia, and weakness of extraocular and frontal muscles with syndactyly of the toes, short stature, prognathism, and hypertrophy and fusion of the eyebrows. [from ORDO]

Clinical features

From HPO
Cutaneous finger syndactyly
MedGen UID:
866898
Concept ID:
C4021254
Congenital Abnormality
A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.
Abnormal foot morphology
MedGen UID:
1762829
Concept ID:
C5399834
Anatomical Abnormality
An abnormality of the skeleton of foot.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Anosmia
MedGen UID:
1950
Concept ID:
C0003126
Finding
An inability to perceive odors. This is a general term describing inability to smell arising in any part of the process of smelling from absorption of odorants into the nasal mucous overlying the olfactory epithelium, diffusion to the cilia, binding to olfactory receptor sites, generation of action potentials in olfactory neurons, and perception of a smell.
Intellectual disability, borderline
MedGen UID:
507499
Concept ID:
C0006009
Finding
Borderline intellectual disability is defined as an intelligence quotient (IQ) in the range of 70-85.
Frontalis muscle weakness
MedGen UID:
347143
Concept ID:
C1859438
Finding
Reduced strength of the frontalis muscle (which is located on the forehead).
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Hypertropia
MedGen UID:
43790
Concept ID:
C0020575
Disease or Syndrome
A type of strabismus characterized by permanent upward deviation of the visual axis of one eye.
Weak extraocular muscles
MedGen UID:
347141
Concept ID:
C1859436
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBlepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome
Follow this link to review classifications for Blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome in Orphanet.

Professional guidelines

PubMed

Gravholt CH, Viuff MH, Brun S, Stochholm K, Andersen NH
Nat Rev Endocrinol 2019 Oct;15(10):601-614. Epub 2019 Jun 18 doi: 10.1038/s41574-019-0224-4. PMID: 31213699
Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, Sas TCJ, Silberbach M, Söderström-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF; International Turner Syndrome Consensus Group
Eur J Endocrinol 2017 Sep;177(3):G1-G70. doi: 10.1530/EJE-17-0430. PMID: 28705803
Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines
Endocr Pract 2016 Jul;22 Suppl 3:1-203. Epub 2016 May 24 doi: 10.4158/EP161365.GL. PMID: 27219496

Recent clinical studies

Etiology

Grunauer M, Jorge AAL
Growth Horm IGF Res 2018 Feb;38:29-33. Epub 2017 Dec 6 doi: 10.1016/j.ghir.2017.12.003. PMID: 29249624
Meazza C, Gertosio C, Giacchero R, Pagani S, Bozzola M
Ital J Pediatr 2017 Aug 3;43(1):66. doi: 10.1186/s13052-017-0385-5. PMID: 28774346Free PMC Article
Geister KA, Camper SA
Annu Rev Genomics Hum Genet 2015;16:199-227. Epub 2015 Apr 22 doi: 10.1146/annurev-genom-090314-045904. PMID: 25939055Free PMC Article
Ashwell M, Gunn P, Gibson S
Obes Rev 2012 Mar;13(3):275-86. Epub 2011 Nov 23 doi: 10.1111/j.1467-789X.2011.00952.x. PMID: 22106927
Verge CF, Mowat D
Arch Dis Child 2010 Jun;95(6):458-63. Epub 2010 Apr 6 doi: 10.1136/adc.2009.157693. PMID: 20371592

Diagnosis

Ranke MB
Front Endocrinol (Lausanne) 2021;12:720419. Epub 2021 Sep 1 doi: 10.3389/fendo.2021.720419. PMID: 34539573Free PMC Article
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Rogol AD, Hayden GF
J Pediatr 2014 May;164(5 Suppl):S1-14.e6. doi: 10.1016/j.jpeds.2014.02.027. PMID: 24731744
Ashwell M, Gunn P, Gibson S
Obes Rev 2012 Mar;13(3):275-86. Epub 2011 Nov 23 doi: 10.1111/j.1467-789X.2011.00952.x. PMID: 22106927
Verge CF, Mowat D
Arch Dis Child 2010 Jun;95(6):458-63. Epub 2010 Apr 6 doi: 10.1136/adc.2009.157693. PMID: 20371592

Therapy

Tamburrino F, Scarano E, Schiavariello C, Perri A, Pession A, Mazzanti L
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):471-477. Epub 2022 Nov 19 doi: 10.1002/ajmg.c.32013. PMID: 36401574
Ranke MB
Front Endocrinol (Lausanne) 2021;12:720419. Epub 2021 Sep 1 doi: 10.3389/fendo.2021.720419. PMID: 34539573Free PMC Article
Şıklar Z, Berberoğlu M
J Clin Res Pediatr Endocrinol 2014;6(1):1-8. doi: 10.4274/Jcrpe.1149. PMID: 24637303Free PMC Article
Bajpai A, Menon PS
Indian J Pediatr 2005 Feb;72(2):139-44. doi: 10.1007/BF02760699. PMID: 15758537
Wit JM
Best Pract Res Clin Endocrinol Metab 2002 Sep;16(3):483-503. doi: 10.1053/beem.2002.0206. PMID: 12464230

Prognosis

Lanvin PL, Goronflot T, Isidor B, Nizon M, Durand B, El Chehadeh S, Geneviève D, Ruault V, Fradin M, Pasquier L, Thévenon J, Delobel B, Burglen L, Afenjar A, Faivre L, Francannet C, Guerrot AM, Goldenberg A, Mercier S, Héron D, Lehalle D, Mignot C, Marey I, Charles P, Moutton S, Bézieau S, Bayat A, Piton A, Willems M, Vincent M
Am J Med Genet A 2024 Jan;194(1):9-16. Epub 2023 Sep 22 doi: 10.1002/ajmg.a.63412. PMID: 37740550
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Al Shaikh A, Daftardar H, Alghamdi AA, Jamjoom M, Awidah S, Ahmed ME, Soliman AT
Acta Biomed 2020 Mar 19;91(1):29-40. doi: 10.23750/abm.v91i1.9182. PMID: 32191651Free PMC Article
Marshall JD, Beck S, Maffei P, Naggert JK
Eur J Hum Genet 2007 Dec;15(12):1193-202. Epub 2007 Oct 17 doi: 10.1038/sj.ejhg.5201933. PMID: 17940554
Ambler G
Best Pract Res Clin Endocrinol Metab 2002 Sep;16(3):519-46. doi: 10.1053/beem.2002.0207. PMID: 12464232

Clinical prediction guides

Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
De Sanctis V, Soliman AT, Di Maio S, Soliman N, Elsedfy H
Acta Biomed 2019 Sep 6;90(3):345-359. doi: 10.23750/abm.v90i3.8736. PMID: 31580327Free PMC Article
Meazza C, Gertosio C, Giacchero R, Pagani S, Bozzola M
Ital J Pediatr 2017 Aug 3;43(1):66. doi: 10.1186/s13052-017-0385-5. PMID: 28774346Free PMC Article
Geister KA, Camper SA
Annu Rev Genomics Hum Genet 2015;16:199-227. Epub 2015 Apr 22 doi: 10.1146/annurev-genom-090314-045904. PMID: 25939055Free PMC Article
Wit JM
Best Pract Res Clin Endocrinol Metab 2002 Sep;16(3):483-503. doi: 10.1053/beem.2002.0206. PMID: 12464230

Recent systematic reviews

Shaki D, Hershkovitz E, Tamam S, Bollotin A, David O, Yalovitsky G, Loewenthal N, Carmon L, Walker D, Nowak R, Haim A
Front Endocrinol (Lausanne) 2023;14:1135768. Epub 2023 Apr 21 doi: 10.3389/fendo.2023.1135768. PMID: 37152958Free PMC Article
Rossboth S, Lechleitner M, Oberaigner W
Endocrinol Diabetes Metab 2021 Jan;4(1):e00175. Epub 2020 Aug 17 doi: 10.1002/edm2.175. PMID: 33532615Free PMC Article
Neal BS, Lack SD, Lankhorst NE, Raye A, Morrissey D, van Middelkoop M
Br J Sports Med 2019 Mar;53(5):270-281. Epub 2018 Sep 21 doi: 10.1136/bjsports-2017-098890. PMID: 30242107
Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, Sas TCJ, Silberbach M, Söderström-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF; International Turner Syndrome Consensus Group
Eur J Endocrinol 2017 Sep;177(3):G1-G70. doi: 10.1530/EJE-17-0430. PMID: 28705803
Ashwell M, Gunn P, Gibson S
Obes Rev 2012 Mar;13(3):275-86. Epub 2011 Nov 23 doi: 10.1111/j.1467-789X.2011.00952.x. PMID: 22106927

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