Format

Send to:

Choose Destination

Lethal congenital contracture syndrome 1(LCCS1)

MedGen UID:
344338
Concept ID:
C1854664
Disease or Syndrome
Synonyms: LCCS1; Lethal autosomal recessive syndrome of multiple congenital contractures; Multiple contracture syndrome, Finnish type
SNOMED CT: Lethal congenital contracture syndrome type 1 (715418007); Herva disease (715418007); Multiple contracture syndrome Finnish type (715418007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM
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).
 
Gene (location): GLE1 (9q34.11)
 
Monarch Initiative: MONDO:0009670
OMIM®: 253310
Orphanet: ORPHA1486

Definition

Autosomal recessive lethal congenital contracture syndrome (LCCS) is the most severe, neonatally lethal, form of arthrogryposis (see 108120), a disorder characterized by congenital nonprogressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). Genetic Heterogeneity of Lethal Congenital Contracture Syndrome See also lethal congenital contracture syndrome-2 (LCCS2; 607598), caused by mutation in the ERBB3 gene (190151); LCCS3 (611369), caused by mutation in the PIP5K1C gene (606102); LCCS4 (614915), caused by mutation in the MYBPC1 gene (160794); LCCS5 (615368), caused by mutation in the DNM2 gene (602378); LCCS6 (616248), caused by mutation in the ZBTB42 gene (613915); LCCS7 (616286), caused by mutation in the CNTNAP1 gene (602346); LCCS8 (616287), caused by mutation in the ADCY6 gene (600294); LCCS9 (616503), caused by mutation in the ADGRG6 gene (612243); LCCS10 (617022), caused by mutation in the NEK9 gene (609798); and LCCS11 (617194), caused by mutation in the GLDN gene (608603). [from OMIM]

Clinical features

From HPO
Paucity of anterior horn motor neurons
MedGen UID:
392895
Concept ID:
C2673351
Finding
Arthrogryposis multiplex congenita
MedGen UID:
2455
Concept ID:
C0003886
Finding
A group of disorders characterized by congenital limb contractures manifesting as limitation of movement of multiple limb joints at birth that is usually non-progressive and may include muscle weakness and fibrosis. This disorder is always associated with decreased intrauterine fetal movement which leads secondarily to the contractures.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypoplasia of the musculature
MedGen UID:
66010
Concept ID:
C0240414
Finding
Underdevelopment of the musculature.
Skeletal muscle atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Widening of cervical spinal canal
MedGen UID:
813921
Concept ID:
C3807591
Finding
Abnormal thorax morphology
MedGen UID:
867424
Concept ID:
C4021797
Anatomical Abnormality
Any abnormality of the thorax (the region of the body formed by the sternum, the thoracic vertebrae and the ribs).
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Abnormality of the amniotic fluid
MedGen UID:
488828
Concept ID:
C0266781
Finding
Abnormality of the amniotic fluid, which is the fluid contained in the amniotic sac surrounding the developing fetus.

Recent clinical studies

Diagnosis

Cerino M, Di Meglio C, Albertini F, Audic F, Riccardi F, Boulay C, Philip N, Bartoli M, Lévy N, Krahn M, Chabrol B
Mol Genet Genomic Med 2020 Aug;8(8):e1277. Epub 2020 Jun 14 doi: 10.1002/mgg3.1277. PMID: 32537934Free PMC Article
Smith C, Parboosingh JS, Boycott KM, Bönnemann CG, Mah JK; Care4Rare Canada Consortium., Lamont RE, Micheil Innes A, Bernier FP
Clin Genet 2017 Mar;91(3):426-430. Epub 2017 Jan 30 doi: 10.1111/cge.12876. PMID: 27684565

Prognosis

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
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
Said E, Chong JX, Hempel M, Denecke J, Soler P, Strom T, Nickerson DA, Kubisch C; University of Washington Center for Mendelian Genomics., Bamshad MJ, Lessel D
Am J Med Genet A 2017 Nov;173(11):3098-3103. Epub 2017 Sep 8 doi: 10.1002/ajmg.a.38406. PMID: 28884921Free PMC Article
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 prediction guides

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
Said E, Chong JX, Hempel M, Denecke J, Soler P, Strom T, Nickerson DA, Kubisch C; University of Washington Center for Mendelian Genomics., Bamshad MJ, Lessel D
Am J Med Genet A 2017 Nov;173(11):3098-3103. Epub 2017 Sep 8 doi: 10.1002/ajmg.a.38406. PMID: 28884921Free PMC Article
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
Jao LE, Appel B, Wente SR
Development 2012 Apr;139(7):1316-26. Epub 2012 Feb 22 doi: 10.1242/dev.074344. PMID: 22357925Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center