Lethal arthrogryposis with anterior horn cell disease (LAAHD) is an autosomal recessive

Recessive

In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...

 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 reduced mobility of the foetus and early death.

Characteristics

LAAHD resembles LCCS1

Lethal congenital contracture syndrome

Lethal congenital contracture syndrome 1 , 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...

 disease but the phenotype

Phenotype

A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

 is milder, with survival beyond 32nd gestational week. However, the foetuses are often stillborn

Stillbirth

A stillbirth occurs when a fetus has died in the uterus. The Australian definition specifies that fetal death is termed a stillbirth after 20 weeks gestation or the fetus weighs more than . Once the fetus has died the mother still has contractions and remains undelivered. The term is often used in...

 or survive only few minutes. The movements of the foetus during pregnancy are scanty and stiff, often only in upper limbs. The malpositions are distal. The inwards spiral and especially the elbow contractures are less severe than in LCCS1 disease. Some patients have intrauterine long bone fractures. Skeletal muscles are affected and show neurogenic atrophy

Atrophy

Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...

. The size and shape of spinal cord at different levels are normal but anterior horn motoneurons are diminished in number and degenerated.

Population genetics

LAAHD is one of approximately 40 Finnish heritage diseases

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...

. Families affected by these diseases come from different parts of Finland

Finland

Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...

, and birthplaces of the ancestors of affected individuals do not show geographic clustering.

Molecular genetics

LAAHD disease results from compound heterozygosity of GLE1FinMajor and a missense point mutation in exon 13 (6 cases in 3 families) or a missense mutation in exon 16 ( seven cases in 3 families). One of the latter cases survived 12 weeks, mostly under artificial respiration.