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Arthrogryposis multiplex congenita-whistling face syndrome

MedGen UID:
349231
•Concept ID:
C1859711
•
Disease or Syndrome
Synonyms: Arthrogryposis multiplex congenita whistling face; ARTHROGRYPOSIS, WHISTLING FACE, AND DEVELOPMENTAL RETARDATION; Illium syndrome; Illum syndrome; Lethal autosomal recessive arthrogryposis multiplex congenita with whistling face and calcifications of the nervous system
SNOMED CT: Arthrogryposis multiplex congenita and whistling face syndrome (720514008); Illum syndrome (720514008)
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).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0008825
OMIM®: 208155
Orphanet: ORPHA1150

Definition

An extremely rare type of arthrogryposis multiplex congenita with the combination of multiple joint contractures with movement limitation and microstomia with a whistling appearance of the mouth that may cause feeding, swallowing and speech difficulties, a distinctive expressionless facies, severe developmental delay, central and autonomous nervous system dysfunction, occasionally Pierre-Robin sequence and lethality generally occurring during the first months of life. [from SNOMEDCT_US]

Clinical features

From HPO
Bradycardia
MedGen UID:
140901
•Concept ID:
C0428977
•
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
See: Feature record | Search on this feature
Abnormality of the nervous system
MedGen UID:
105425
•Concept ID:
C0497552
•
Congenital Abnormality
An abnormality of the nervous system.
See: Feature record | Search on this feature
Calcinosis
MedGen UID:
709
•Concept ID:
C0006663
•
Finding
Formation of calcium deposits in any soft tissue.
See: Feature record | Search on this feature
Arthrogryposis multiplex congenita
MedGen UID:
1830310
•Concept ID:
C5779613
•
Disease or Syndrome
Multiple congenital contractures in different body areas.
See: Feature record | Search on this feature
Apnea
MedGen UID:
2009
•Concept ID:
C0003578
•
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
See: Feature record | Search on this feature
Temperature instability
MedGen UID:
329973
•Concept ID:
C1820737
•
Finding
Disordered thermoregulation characterized by an impaired ability to maintain a balance between heat production and heat loss, with resulting instability of body temperature.
See: Feature record | Search on this feature
Isolated Pierre-Robin syndrome
MedGen UID:
19310
•Concept ID:
C0031900
•
Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulaties during the neonatal period (summary by Tan et al., 2013).
See: Feature record | Search on this feature
Excessive salivation
MedGen UID:
11419
•Concept ID:
C0037036
•
Disease or Syndrome
Excessive production of saliva.
See: Feature record | Search on this feature
Whistling appearance
MedGen UID:
338478
•Concept ID:
C1848473
•
Finding
An abnormality of facial morphology characterized by a small mouth opening and constant contraction of the lips as if the patient were whistling.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVArthrogryposis multiplex congenita-whistling face syndrome
Follow this link to review classifications for Arthrogryposis multiplex congenita-whistling face syndrome in Orphanet.

Recent clinical studies

Etiology

A New Aberration in the VPS33B Gene Leads to Full-Symptom ARCS1.
Adamczyk-Gruszka O, Horecka-Lewitowicz A, Zmelonek-Znamirowska A, Gruszka J, Koziel D, Lewitowicz P
Am J Case Rep 2021 Sep 17;22:e932769. doi: 10.12659/AJCR.932769. PMID: 34531360Free PMC Article
Findings, phenotypes, and outcomes in Freeman-Sheldon and Sheldon-Hall syndromes and distal arthrogryposis types 1 and 3: protocol for systematic review and patient-level data meta-analysis.
Poling MI, Morales Corado JA, Chamberlain RL
Syst Rev 2017 Mar 6;6(1):46. doi: 10.1186/s13643-017-0444-4. PMID: 28264711Free PMC Article
Arthrogryposis multiplex congenita and Pena-Shokeir phenotype: challenge of prenatal diagnosis--report of 21 cases, antenatal findings and review.
Hoellen F, Schröer A, Kelling K, Krapp M, Axt-Fliedner R, Gembruch U, Weichert J
Fetal Diagn Ther 2011;30(4):289-98. Epub 2011 Dec 8 doi: 10.1159/000331401. PMID: 22156407
A novel mutation in TNNT3 associated with Sheldon-Hall syndrome in a Chinese family with vertical talus.
Zhao N, Jiang M, Han W, Bian C, Li X, Huang F, Kong Q, Li J
Eur J Med Genet 2011 May-Jun;54(3):351-3. Epub 2011 Mar 12 doi: 10.1016/j.ejmg.2011.03.002. PMID: 21402185
Cerebro-oculo-facio-skeletal syndrome.
Suzumura H, Arisaka O
Adv Exp Med Biol 2010;685:210-4. doi: 10.1007/978-1-4419-6448-9_19. PMID: 20687508

Diagnosis

A rare association of type 2 Duanes retraction syndrome with arthrogryposis multiplex congenita.
Pawar N, Ravindran M, Chakravarthy S, Ramakrishnan R
Strabismus 2021 Mar;29(1):34-36. Epub 2021 Jan 22 doi: 10.1080/09273972.2020.1871380. PMID: 33480805
Freeman-Burian syndrome.
Poling MI, Dufresne CR, Chamberlain RL
Orphanet J Rare Dis 2019 Jan 10;14(1):14. doi: 10.1186/s13023-018-0984-2. PMID: 30630514Free PMC Article
Microdeletion 3q syndrome.
Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F
J Craniofac Surg 2011 Nov;22(6):2124-8. doi: 10.1097/SCS.0b013e3182323cdf. PMID: 22067867
Freeman-Sheldon syndrome--prenatal and postnatal diagnosis.
Hegde SS, Shetty MS, Rama Murthy BS
Indian J Pediatr 2010 Feb;77(2):196-7. Epub 2009 Dec 11 doi: 10.1007/s12098-009-0227-6. PMID: 20012803
Sheldon-Hall syndrome.
Toydemir RM, Bamshad MJ
Orphanet J Rare Dis 2009 Mar 23;4:11. doi: 10.1186/1750-1172-4-11. PMID: 19309503Free PMC Article

Therapy

Findings, phenotypes, and outcomes in Freeman-Sheldon and Sheldon-Hall syndromes and distal arthrogryposis types 1 and 3: protocol for systematic review and patient-level data meta-analysis.
Poling MI, Morales Corado JA, Chamberlain RL
Syst Rev 2017 Mar 6;6(1):46. doi: 10.1186/s13643-017-0444-4. PMID: 28264711Free PMC Article
Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage.
Lavi E, Montone KT, Rorke LB, Kliman HJ
Neurology 1991 Sep;41(9):1467-8. doi: 10.1212/wnl.41.9.1467. PMID: 1891100
The thumb in the congenital malformation syndromes.
Poznanski AK, Garn SM, Holt JF
Radiology 1971 Jul;100(1):115-29. doi: 10.1148/100.1.115. PMID: 5147019

Prognosis

A New Aberration in the VPS33B Gene Leads to Full-Symptom ARCS1.
Adamczyk-Gruszka O, Horecka-Lewitowicz A, Zmelonek-Znamirowska A, Gruszka J, Koziel D, Lewitowicz P
Am J Case Rep 2021 Sep 17;22:e932769. doi: 10.12659/AJCR.932769. PMID: 34531360Free PMC Article
Further delineation of MYO18B-related autosomal recessive Klippel-Feil syndrome with myopathy and facial dysmorphism.
Altuame FD, Haldeman-Englert C, Cupler E, Al Muhaizea MA, Al-Zaidan HI, Hashem M, Alkuraya FS
Am J Med Genet A 2021 Feb;185(2):370-376. Epub 2020 Nov 11 doi: 10.1002/ajmg.a.61957. PMID: 33179433
De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.
Chong JX, McMillin MJ, Shively KM, Beck AE, Marvin CT, Armenteros JR, Buckingham KJ, Nkinsi NT, Boyle EA, Berry MN, Bocian M, Foulds N, Uzielli ML, Haldeman-Englert C, Hennekam RC, Kaplan P, Kline AD, Mercer CL, Nowaczyk MJ, Klein Wassink-Ruiter JS, McPherson EW, Moreno RA, Scheuerle AE, Shashi V, Stevens CA, Carey JC, Monteil A, Lory P, Tabor HK, Smith JD, Shendure J, Nickerson DA; University of Washington Center for Mendelian Genomics, Bamshad MJ
Am J Hum Genet 2015 Mar 5;96(3):462-73. Epub 2015 Feb 12 doi: 10.1016/j.ajhg.2015.01.003. PMID: 25683120Free PMC Article
Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis.
Folkmann AW, Dawson TR, Wente SR
Adv Biol Regul 2014 Jan;54:74-91. Epub 2013 Nov 13 doi: 10.1016/j.jbior.2013.10.002. PMID: 24275432Free PMC Article
Microdeletion 3q syndrome.
Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F
J Craniofac Surg 2011 Nov;22(6):2124-8. doi: 10.1097/SCS.0b013e3182323cdf. PMID: 22067867

Clinical prediction guides

Further delineation of MYO18B-related autosomal recessive Klippel-Feil syndrome with myopathy and facial dysmorphism.
Altuame FD, Haldeman-Englert C, Cupler E, Al Muhaizea MA, Al-Zaidan HI, Hashem M, Alkuraya FS
Am J Med Genet A 2021 Feb;185(2):370-376. Epub 2020 Nov 11 doi: 10.1002/ajmg.a.61957. PMID: 33179433
Freeman-Burian syndrome.
Poling MI, Dufresne CR, Chamberlain RL
Orphanet J Rare Dis 2019 Jan 10;14(1):14. doi: 10.1186/s13023-018-0984-2. PMID: 30630514Free PMC Article
De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.
Chong JX, McMillin MJ, Shively KM, Beck AE, Marvin CT, Armenteros JR, Buckingham KJ, Nkinsi NT, Boyle EA, Berry MN, Bocian M, Foulds N, Uzielli ML, Haldeman-Englert C, Hennekam RC, Kaplan P, Kline AD, Mercer CL, Nowaczyk MJ, Klein Wassink-Ruiter JS, McPherson EW, Moreno RA, Scheuerle AE, Shashi V, Stevens CA, Carey JC, Monteil A, Lory P, Tabor HK, Smith JD, Shendure J, Nickerson DA; University of Washington Center for Mendelian Genomics, Bamshad MJ
Am J Hum Genet 2015 Mar 5;96(3):462-73. Epub 2015 Feb 12 doi: 10.1016/j.ajhg.2015.01.003. PMID: 25683120Free PMC Article
Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis.
Folkmann AW, Dawson TR, Wente SR
Adv Biol Regul 2014 Jan;54:74-91. Epub 2013 Nov 13 doi: 10.1016/j.jbior.2013.10.002. PMID: 24275432Free PMC Article
Clinical analysis of a variant of Freeman-Sheldon syndrome (DA2B).
Krakowiak PA, Bohnsack JF, Carey JC, Bamshad M
Am J Med Genet 1998 Feb 26;76(1):93-8. doi: 10.1002/(sici)1096-8628(19980226)76:1<93::aid-ajmg17>3.0.co;2-k. PMID: 9508073

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