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Lethal congenital contracture syndrome 6(LCCS6)

MedGen UID:
864123
•Concept ID:
C4015686
•
Disease or Syndrome
Synonym: LCCS6
 
Gene (location): ZBTB42 (14q32.33)
 
Monarch Initiative: MONDO:0014549
OMIM®: 616248

Definition

Lethal congenital contracture syndrome-6 (LCCS6) is an autosomal recessive disorder characterized by multiple flexion and extension contractures resulting from lack of fetal movements, severe polyhydramnios, and absent stomach (Patel et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of LCCS, see LCCS1 (253310). [from OMIM]

Clinical features

From HPO
Congenital contracture
MedGen UID:
83066
•Concept ID:
C0332878
•
Congenital Abnormality
One or more flexion contractures (a bent joint that cannot be straightened actively or passively) that are present at birth.
See: Feature record | Search on this feature
Macrocephaly
MedGen UID:
745757
•Concept ID:
C2243051
•
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
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
Polyhydramnios
MedGen UID:
6936
•Concept ID:
C0020224
•
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
See: Feature record | Search on this feature
Decreased fetal movement
MedGen UID:
68618
•Concept ID:
C0235659
•
Finding
An abnormal reduction in quantity or strength of fetal movements.
See: Feature record | Search on this feature
Absence of stomach bubble on fetal sonography
MedGen UID:
869203
•Concept ID:
C4023625
•
Finding
By the 14th week of gestation it is nearly always possible to visualized the fluid-filled fetal stomach bubble on prenatal sonography. This term refers to the absence of a normal fetal stomach bubble on fetal ultrasonography performed at around 16 to 20 weeks' gestation.
See: Feature record | Search on this feature
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Recent clinical studies

Etiology

Absence of Axoglial Paranodal Junctions in a Child With CNTNAP1 Mutations, Hypomyelination, and Arthrogryposis.
Conant A, Curiel J, Pizzino A, Sabetrasekh P, Murphy J, Bloom M, Evans SH, Helman G, Taft RJ, Simons C, Whitehead MT, Moore SA, Vanderver A
J Child Neurol 2018 Sep;33(10):642-650. Epub 2018 Jun 8 doi: 10.1177/0883073818776157. PMID: 29882456Free PMC Article
Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway.
Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS
Am J Hum Genet 2007 Sep;81(3):589-95. Epub 2007 Jul 24 doi: 10.1086/520770. PMID: 17701904Free PMC Article
Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.
Pakkasjärvi N, Ritvanen A, Herva R, Peltonen L, Kestilä M, Ignatius J
Am J Med Genet A 2006 Sep 1;140A(17):1834-9. doi: 10.1002/ajmg.a.31381. PMID: 16892327
Lethal arthrogryposis in Finland--a clinico-pathological study of 83 cases during thirteen years.
Vuopala K, Leisti J, Herva R
Neuropediatrics 1994 Dec;25(6):308-15. doi: 10.1055/s-2008-1073045. PMID: 7770128

Diagnosis

Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures.
Turgut GT, Altunoglu U, Gulec C, Sarac Sivrikoz T, Kalaycı T, Toksoy G, Avcı Ş, Yıldırım BT, Sayın GY, Kalelioglu IH, Karaman B, Has R, Başaran S, Yuksel A, Kayserili H, Uyguner ZO
Clin Genet 2024 Jun;105(6):596-610. Epub 2024 Jan 26 doi: 10.1111/cge.14490. PMID: 38278647
Spine deformities in rare congenital syndromes: clinical issues.
Campbell RM Jr
Spine (Phila Pa 1976) 2009 Aug 1;34(17):1815-27. doi: 10.1097/BRS.0b013e3181ab64e9. PMID: 19644333
Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.
Pakkasjärvi N, Ritvanen A, Herva R, Peltonen L, Kestilä M, Ignatius J
Am J Med Genet A 2006 Sep 1;140A(17):1834-9. doi: 10.1002/ajmg.a.31381. PMID: 16892327
Atelencephalic microcephaly: a case report and review of the literature.
Ippel PF, Breslau-Siderius EJ, Hack WW, van der Blij HF, Bouve S, Bijlsma JB
Eur J Pediatr 1998 Jun;157(6):493-7. doi: 10.1007/s004310050861. PMID: 9667407
Lethal arthrogryposis in Finland--a clinico-pathological study of 83 cases during thirteen years.
Vuopala K, Leisti J, Herva R
Neuropediatrics 1994 Dec;25(6):308-15. doi: 10.1055/s-2008-1073045. PMID: 7770128

Prognosis

Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6.
Agolini E, Cherchi C, Bellacchio E, Martinelli D, Cocciadiferro D, Cutrera R, Chiarini Testa MB, Barone C, Bianca S, Novelli A
Clin Genet 2020 Apr;97(4):649-654. Epub 2020 Feb 20 doi: 10.1111/cge.13691. PMID: 31846058
A homozygous I684T in GLE1 as a novel cause of arthrogryposis and motor neuron loss.
Paakkola T, Vuopala K, Kokkonen H, Ignatius J, Valkama M, Moilanen JS, Fahiminiya S, Majewski J, Hinttala R, Uusimaa J
Clin Genet 2018 Jan;93(1):173-177. Epub 2017 Nov 24 doi: 10.1111/cge.13086. PMID: 28657126
NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations.
Bend EG, Si Y, Stevenson DA, Bayrak-Toydemir P, Newcomb TM, Jorgensen EM, Swoboda KJ
Neurology 2016 Sep 13;87(11):1131-9. Epub 2016 Aug 24 doi: 10.1212/WNL.0000000000003095. PMID: 27558372Free PMC Article
Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway.
Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS
Am J Hum Genet 2007 Sep;81(3):589-95. Epub 2007 Jul 24 doi: 10.1086/520770. PMID: 17701904Free PMC Article

Clinical prediction guides

Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures.
Turgut GT, Altunoglu U, Gulec C, Sarac Sivrikoz T, Kalaycı T, Toksoy G, Avcı Ş, Yıldırım BT, Sayın GY, Kalelioglu IH, Karaman B, Has R, Başaran S, Yuksel A, Kayserili H, Uyguner ZO
Clin Genet 2024 Jun;105(6):596-610. Epub 2024 Jan 26 doi: 10.1111/cge.14490. PMID: 38278647
Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6.
Agolini E, Cherchi C, Bellacchio E, Martinelli D, Cocciadiferro D, Cutrera R, Chiarini Testa MB, Barone C, Bianca S, Novelli A
Clin Genet 2020 Apr;97(4):649-654. Epub 2020 Feb 20 doi: 10.1111/cge.13691. PMID: 31846058
Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway.
Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS
Am J Hum Genet 2007 Sep;81(3):589-95. Epub 2007 Jul 24 doi: 10.1086/520770. PMID: 17701904Free PMC Article

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    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
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