Lethal congenital contracture syndrome
Encyclopedia
Lethal congenital contracture syndrome 1 (LCCS1), also called Multiple contracture syndrome, Finnish type, is an autosomal
recessive genetic disorder
characterized by total immobility of a fetus, detectable at around the 13th week of pregnancy. LCCS1 invariably leads to prenatal death before the 32nd gestational week. LCCS1 is one of 40 Finnish heritage disease
s. It was first described in 1985 and since then, approximately 70 cases have been diagnosed.
, and is detectable at 13th week of pregnancy
. It is accompanied by oedema, small chin, small lungs, crooked joints and occasional skin webs of the neck and elbows. The fetus has characteristic pattern of malpositions recognizable even in severely macerated fetuses with club feet and hyperextension of the knees but the elbows and wrists showing flexion contractures.
Neuropathological analysis shows lack of anterior horn motoneurons and severe atrophy of the ventral spinal cord. The skeletal muscles are severely hypoplastic.
at chromosome
9q34. In more than 40 families the fetus has been homozygous for A->G substitution (c.432-10A>G) located in intron 3 of GLE1 creating an illegitimate splice acceptor site resulting in nine extra nucleotides in the GLE1 cDNA (GLE1 FinMajor mutation). In one family the fetus has been compound heterozygous for GLE1 FinMajor and R→H substitution in exon 12.
A slightly milder phenotype with survival beyond 32nd gestational week also characterized by foetal akinesia, arthrogryposis and anterior horn cell loss (Lethal arthrogryposis with anterior horn cell disease
, LAAHD) was also shown to be allelic to LCCS1 and result from mutations in GLE1.
LCCS1 is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder (GLE1) is located on an autosome
(chromosome 9), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
characterized by total immobility of a fetus, detectable at around the 13th week of pregnancy. LCCS1 invariably leads to prenatal death before the 32nd gestational week. LCCS1 is one of 40 Finnish heritage disease
Finnish heritage disease
A Finnish heritage disease is a genetic disease or disorder that is part of the Finnish disease heritage. Finnish heritage diseases are significantly more common in people whose ancestors were ethnic Finns, natives of Finland and Sweden. About 40 rare diseases are regarded as Finnish heritage...
s. It was first described in 1985 and since then, approximately 70 cases have been diagnosed.
Characteristics
LCCS1 is characterized by total lack of the movements of the fetusFetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
, and is detectable at 13th week of pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
. It is accompanied by oedema, small chin, small lungs, crooked joints and occasional skin webs of the neck and elbows. The fetus has characteristic pattern of malpositions recognizable even in severely macerated fetuses with club feet and hyperextension of the knees but the elbows and wrists showing flexion contractures.
Neuropathological analysis shows lack of anterior horn motoneurons and severe atrophy of the ventral spinal cord. The skeletal muscles are severely hypoplastic.
Cause
The defective gene associated with LCCS1 is mRNA export mediator GLE1GLE1L
Nucleoporin GLE1 is a protein that in humans is encoded by the GLE1 gene on chromosome 9.- Mutation & Diseases :A genome-wide screening and linkage analysis assigned the disease locus of lethal congenital contracture syndrome, one of 40 Finnish heritage diseases, to a defined region of 9q34, where...
at chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
9q34. In more than 40 families the fetus has been homozygous for A->G substitution (c.432-10A>G) located in intron 3 of GLE1 creating an illegitimate splice acceptor site resulting in nine extra nucleotides in the GLE1 cDNA (GLE1 FinMajor mutation). In one family the fetus has been compound heterozygous for GLE1 FinMajor and R→H substitution in exon 12.
A slightly milder phenotype with survival beyond 32nd gestational week also characterized by foetal akinesia, arthrogryposis and anterior horn cell loss (Lethal arthrogryposis with anterior horn cell disease
Lethal arthrogryposis with anterior horn cell disease
Lethal arthrogryposis with anterior horn cell disease is an autosomal recessive genetic disorder characterized by reduced mobility of the foetus and early death.-Characteristics:...
, LAAHD) was also shown to be allelic to LCCS1 and result from mutations in GLE1.
Genetics
LCCS1 is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder (GLE1) is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
(chromosome 9), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
Genetic carrier
A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.