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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 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)

Gene (location): Gene(s) directly associated with this condition or phenotype.	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

See: Feature record | Search on this feature

Micrognathia

MedGen UID:: 44428
•Concept ID:: C0025990
•: Congenital Abnormality

Developmental hypoplasia of the mandible.

See: Feature record | Search on this feature

Hypoplasia of the musculature

MedGen UID:: 66010
•Concept ID:: C0240414
•: Finding

Underdevelopment of the musculature.

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Muscular atrophy

MedGen UID:: 892680
•Concept ID:: C0541794
•: Pathologic Function

The presence of skeletal muscular atrophy (which is also known as amyotrophy).

See: Feature record | Search on this feature

Widening of cervical spinal canal

MedGen UID:: 813921
•Concept ID:: C3807591
•: Finding

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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).

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Arthrogryposis multiplex congenita

MedGen UID:: 1830310
•Concept ID:: C5779613
•: Disease or Syndrome

Multiple congenital contractures in different body areas.

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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.

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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.

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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.

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Abnormality of metabolism/homeostasis
- Edema
Abnormality of prenatal development or birth
- Abnormality of the amniotic fluid
Abnormality of the musculoskeletal system
Abnormality of the nervous system
- Paucity of anterior horn motor neurons
Abnormality of the respiratory system
- Pulmonary hypoplasia

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVLethal congenital contracture syndrome 1

Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability
- Lethal congenital contracture syndrome 1

Follow this link to review classifications for Lethal congenital contracture syndrome 1 in Orphanet.

Recent clinical studies

Etiology

Falling through the cracks: Failing to identify compromised Miranda abilities for defendants with limited cognitive capacities.

Tazi KY, Rogers R
Behav Sci Law 2023 Sep-Oct;41(5):326-342. Epub 2023 Mar 2 doi: 10.1002/bsl.2610. PMID: 36866414

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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: 32537934 Free PMC Article

Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum.

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

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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

Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1.

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: 28884921 Free 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: 24275432 Free PMC Article

See all (4)