Lethal Congenital Contracture Syndrome 1 (LCCS1)

External Ids:

GARD: ¹⁹ Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.

MalaCards based summary: Lethal Congenital Contracture Syndrome 1, also known as multiple contracture syndrome, finnish type, is related to lethal congenital contracture syndrome 3 and lethal congenital contracture syndrome 2. An important gene associated with Lethal Congenital Contracture Syndrome 1 is GLE1 (GLE1 RNA Export Mediator), and among its related pathways/superpathways are Metabolism and Transport of the SLBP independent Mature mRNA. Affiliated tissues include skeletal muscle, spinal cord and bone, and related phenotypes are hypertelorism and short stature

Orphanet: ⁵⁸ Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.

UniProtKB/Swiss-Prot: ⁷³ A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non- progressive joint contractures (arthrogryposis). 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. LCCS1 patients manifest early fetal hydrops and akinesia, micrognathia, pulmonary hypoplasia, pterygia, and multiple joint contractures. It leads to prenatal death.

OMIM®: ⁵⁷ 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). (253310) (Updated 08-Dec-2022)

Disease Ontology: ¹¹ A lethal congenital contracture syndrome that has material basis in homozygous or compound heterozygous mutation in the mRNA export mediator GLE1 on chromosome 9q34.

Clinical features from OMIM®:

Search Clinical Trials, NIH Clinical Center for Lethal Congenital Contracture Syndrome 1