Prepair 1000+

Gene: GLE1

Green List (high evidence)

Autosomal recessive lethal congenital contracture syndrome (LCCS) is the most severe, neonatally lethal, form of arthrogryposis, characterized by congenital nonprogressive joint contractures which involve the upper or lower limbs and/or the vertebral column. Characterised by total immobility of the fetus, detectable at the 13th week of
pregnancy, accompanied by hydrops, micrognatia, pulmonary hypoplasia, pterygia and multiple joint contractures. It invariably leads to prenatal death before the 32nd gestational week. Neuropathological analysis shows lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and hypoplastic, nearly absent skeletal muscles. The carrier frequency in northeastern Finland, where most of the families with LCCS1 originate, was 2%.
Congenital arthrogryposis with anterior horn cell disease (CAAHD) is an autosomal recessive neuromuscular disorder with highly variable severity. Affected individuals are usually noted to have contractures in utero on prenatal ultrasound studies, and present at birth with generalized contractures manifest as arthrogryposis multiplex congenita. Patients have severe hypotonia with respiratory insufficiency, often resulting in death in infancy or early childhood. Some patients may survive into later childhood with supportive care, but may be unable to walk or sit independently due to a combination of muscle weakness and contractures. Cognition may be normal.
There is controversy as to whether the two phenotypes represent a genotype/phenotype correlation rather than 2 different disease entities. Homozygotes for the FinMajor founder mutation show a more severe phenotype than compound heterozygotes.
Functional evidence from zebrafish model.

Created: 4 Nov 2024, 6:40 a.m. | Last Modified: 4 Nov 2024, 6:40 a.m.

Panel Version: 1.546

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital arthrogryposis with anterior horn cell disease, MIM #611890; Lethal congenital contracture syndrome 1, MIM #253310

Publications

• PMID: 18204449
• 22357925
• 32537934