U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Lethal congenital contracture syndrome 8(LCCS8)

MedGen UID:
896058
•Concept ID:
C4225385
•
Disease or Syndrome
Synonym: LCCS8
 
Gene (location): ADCY6 (12q13.12)
 
Monarch Initiative: MONDO:0014570
OMIM®: 616287

Definition

Lethal congenital contracture syndrome-8 (LCCS8), an axoglial form of arthrogryposis multiplex congenita, is characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period (Laquerriere et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of lethal congenital contracture syndrome, see LCCS1 (253310). [from OMIM]

Clinical features

From HPO
Oral-pharyngeal dysphagia
MedGen UID:
120596
•Concept ID:
C0267071
•
Disease or Syndrome
Difficulty in swallowing due to an abnormality in the mouth or throat.
See: Feature record | Search on this feature
Areflexia
MedGen UID:
115943
•Concept ID:
C0234146
•
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
See: Feature record | Search on this feature
Arthrogryposis multiplex congenita
MedGen UID:
2455
•Concept ID:
C0003886
•
Finding
Multiple congenital contractures in different body areas.
See: Feature record | Search on this feature
Hypotonia
MedGen UID:
10133
•Concept ID:
C0026827
•
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
See: Feature record | Search on this feature
Flexion contracture
MedGen UID:
83069
•Concept ID:
C0333068
•
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
See: Feature record | Search on this feature
Facial diplegia
MedGen UID:
322796
•Concept ID:
C1836003
•
Finding
Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy).
See: Feature record | Search on this feature
Generalized hypotonia
MedGen UID:
346841
•Concept ID:
C1858120
•
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
See: Feature record | Search on this feature
Show allHide all

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 contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway.
Narkis G, Ofir R, Landau D, Manor E, Volokita M, Hershkowitz R, Elbedour K, Birk OS
Am J Hum Genet 2007 Sep;81(3):530-9. Epub 2007 Jul 24 doi: 10.1086/520771. PMID: 17701898Free PMC Article

Diagnosis

Extension of the phenotypic spectrum of GLE1-related disorders to a mild congenital form resembling congenital myopathy.
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
Expanding the MYBPC1 phenotypic spectrum: a novel homozygous mutation causes arthrogryposis multiplex congenita.
Ekhilevitch N, Kurolap A, Oz-Levi D, Mory A, Hershkovitz T, Ast G, Mandel H, Baris HN
Clin Genet 2016 Jul;90(1):84-9. Epub 2016 Jan 20 doi: 10.1111/cge.12707. PMID: 26661508
New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update.
Navarro CL, Esteves-Vieira V, Courrier S, Boyer A, Duong Nguyen T, Huong le TT, Meinke P, Schröder W, Cormier-Daire V, Sznajer Y, Amor DJ, Lagerstedt K, Biervliet M, van den Akker PC, Cau P, Roll P, Lévy N, Badens C, Wehnert M, De Sandre-Giovannoli A
Eur J Hum Genet 2014 Aug;22(8):1002-11. Epub 2013 Oct 30 doi: 10.1038/ejhg.2013.258. PMID: 24169522Free PMC Article

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
Restrictive Dermopathy: Four Case Reports and Structural Skin Changes.
Bidier M, Salz M, Meyburg J, Elbe-Bürger A, Lasitzschka F, Hausser I, Schäkel K
Acta Derm Venereol 2018 Aug 29;98(8):807-808. doi: 10.2340/00015555-2970. PMID: 29774364
New lethal skeletal dysplasia with Dandy-Walker malformation, congenital heart defects, abnormal thumbs, hypoplastic genitalia, and distinctive facies.
Stevens CA, Lachman RS
Am J Med Genet A 2010 Aug;152A(8):1915-8. doi: 10.1002/ajmg.a.33488. PMID: 20602491Free PMC Article

Clinical prediction guides

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
Expanding the MYBPC1 phenotypic spectrum: a novel homozygous mutation causes arthrogryposis multiplex congenita.
Ekhilevitch N, Kurolap A, Oz-Levi D, Mory A, Hershkovitz T, Ast G, Mandel H, Baris HN
Clin Genet 2016 Jul;90(1):84-9. Epub 2016 Jan 20 doi: 10.1111/cge.12707. PMID: 26661508

Supplemental Content

Table of contents

    Clinical resources

    Consumer resources

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...