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

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 Sweden

Sweden

Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....

. About 40 rare disease

Rare disease

A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...

s are regarded as Finnish heritage diseases. None of these diseases are restricted to Finns; rather, they are genetic diseases with far wider distribution in the world, but due to founder effect

Founder effect

In population genetics, the founder effect is the loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger population. It was first fully outlined by Ernst Mayr in 1942, using existing theoretical work by those such as Sewall...

s and genetic isolation

Genetic isolate

A genetic isolate is population of organisms that has little genetic mixing with other organisms within the same species. This may result in speciation, but this is not necessarily the case...

they are more common in Finns.

Within Finland

Finland

these diseases are more common in the east and north, consistent with their higher association with ethnic Finns than with ethnic Swedes. The Finnish disease heritage does not extend to other ethnic groups in the region, the Sámi

Sami people

The Sami people, also spelled Sámi, or Saami, are the arctic indigenous people inhabiting Sápmi, which today encompasses parts of far northern Sweden, Norway, Finland, the Kola Peninsula of Russia, and the border area between south and middle Sweden and Norway. The Sámi are Europe’s northernmost...

and Karelians

Karelians

The Karelians are a Baltic-Finnic ethnic group living mostly in the Republic of Karelia and in other north-western parts of the Russian Federation. The historic homeland of Karelians includes also parts of present-day Eastern Finland and the formerly Finnish territory of Ladoga Karelia...

other than Finnish Karelians. It is attributed to a population bottleneck

Population bottleneck

A population bottleneck is an evolutionary event in which a significant percentage of a population or species is killed or otherwise prevented from reproducing....

among ancestors of modern Finns, estimated to have occurred about 4000 years ago, presumably when populations practicing agriculture and animal husbandry arrived in Finland.

In Finland about one in five persons carries a gene defect associated with at least one Finnish heritage disease, and about one in 500 children born is affected. Most of the gene defects are 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...

s, so that if both the mother and father carry the same defect, the chance that their child will have the associated disease is 1 in 4. The molecular genetics

Molecular genetics

Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...

of many of these diseases have been determined, enabling genetic testing

Genetic testing

Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...

, prenatal testing, and counseling. This in turn has raised questions of bioethics

Bioethics

Bioethics is the study of controversial ethics brought about by advances in biology and medicine. Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, and philosophy....

and eugenics

Eugenics

Eugenics is the "applied science or the bio-social movement which advocates the use of practices aimed at improving the genetic composition of a population", usually referring to human populations. The origins of the concept of eugenics began with certain interpretations of Mendelian inheritance,...

Finnish heritage diseases include:

APECED (autoimmune polyendocrinopathy—candidosis—ectodermal dystrophy)
Aspartylglucosaminuria
Aspartylglucosaminuria
Aspartylglucosaminuria , also called aspartylglycosaminuria, is a rare, autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme N-aspartyl-beta-glucosaminidase . This enzyme normally cleaves long sugar chains known as oligosaccharides in the lysosome...

, a lysosomal storage disease
Lysosomal storage disease
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function...
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
Congenital nephrotic syndrome
Congenital nephrotic syndrome
Congenital nephrotic syndrome is an inherited disorder characterized by protein in the urine and swelling of the body.-Causes:Congenital nephrotic syndrome is a very rare form of nephrotic syndrome. It occurs predominantly in families of Finnish origin and manifests shortly after birth. It is an...

, a kidney disease of newborn babies
Congenital chloride diarrhea
Congenital chloride diarrhea
Congenital chloride diarrhea is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma , a gene that encodes a membrane protein of intestinal cells. The protein belongs to the solute carrier 26 family of membrane transport proteins...
Congenital stromal corneal dystrophy
Congenital stromal corneal dystrophy
Congenital stromal corneal dystrophy , also called Witschel dystrophy, is an extremely rare, autosomal dominant form of human corneal dystrophy. It is non-progressive and is linked to mutations in DCN gene encoding decorin protein. Only 4 families have been reported to have the disease by 2009...
GRACILE syndrome
GRACILE syndrome
GRACILE syndrome is an autosomal recessive genetic disorder, one of the Finnish heritage diseases. It is caused by mutation in BCS1L gene.GRACILE is an acronym for growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death...
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:...
Lethal congenital contracture syndrome 1
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...
Meretoja syndrome
Meckel syndrome
Meckel syndrome
Meckel syndrome is a rare, lethal, ciliopathic, genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations, polydactyly, hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.Meckel-Gruber syndrome is named for Johann...
Myotonia congenita
Myotonia congenita
Congenital myotonia is a genetic, neuromuscular channelopathy that affects skeletal muscles . It is congenital, meaning that it is present from birth. Amongst other problems, it causes delayed relaxation of the muscles and rigidity...
Nonketotic hyperglycinemia
Salla disease
Salla disease
Salla disease , also called sialic acid storage disease or Finnish type sialuria, is an autosomal recessive lysosomal storage disease characterized by early physical impairment and mental retardation. It was first described in 1979, after Salla, a municipality in Finnish Lapland...

, a lysosomal storage disease
Lysosomal storage disease
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function...
PEHO syndrome
PEHO syndrome
PEHO syndrome is a progressive encephalopathy with edema, hypsarrhythmia and optic atrophy. It is a very rare disease, one of the Finnish heritage diseases, and has been reported also in Dutch and Swiss infants....
Rapadilino syndrome
Rapadilino syndrome
Rapadilino syndrome is an autosomal recessive congenital disorder characterized by radial and patellar aplasia, short stature, arched or cleft palate, limb malformation, and dislocated joints. It is more prevalent in Finland than elsewhere in the world....
Retinoschisis
Retinoschisis
Retinoschisis is an eye disease characterized by the abnormal splitting of the retina's neurosensory layers, usually in the outer plexiform layer, resulting in a loss of vision in the corresponding visual field in some rarer forms...
Usher syndrome
Usher syndrome
Usher syndrome is a relatively rare genetic disorder that is a leading cause of deafblindness and that is associated with a mutation in any one of 10 genes. Other names for Usher syndrome include Hallgren syndrome, Usher-Hallgren syndrome, rp-dysacusis syndrome and dystrophia retinae dysacusis...

Three rare causes of dwarfism

Dwarfism

Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....

are included in the Finnish heritage: cartilage-hair hypoplasia

Cartilage-hair hypoplasia

Cartilage–hair hypoplasia , also known as McKusick type metaphyseal chondrodysplasia, is a rare form of short-limbed dwarfism due to skeletal dysplasia. It was first reported in 1965 by McKusick et al...

, diastrophic dysplasia

Diastrophic dysplasia

Diastrophic dysplasia is an autosomal recessive dysplasia which affects cartilage and bone development....

and Mulibrey nanism

Mulibrey nanism

Mulibrey nanism , also called Perheentupa syndrome and pericardial constriction with growth failure, is a rare autosomal recessive congenital disorder. It causes severe growth failure along with abnormalities of the heart, muscle, liver, brain and eye...

.

Four genetically distinct subtypes of neuronal ceroid lipofuscinosis

Neuronal Ceroid Lipofuscinosis

Neuronal Ceroid Lipofuscinoses is the general name for a family of at least eight genetically separate neurodegenerative disorders that result from excessive accumulation of lipopigments in the body's tissues. These lipopigments are made up of fats and proteins...

are enriched in Finns: CLN1, CLN3

CLN3

Battenin is a protein that in humans is encoded by the CLN3 gene located on chromosome 16.- Function :Battenin is involved in lysosomal function. Many alternatively spliced transcript variants have been found for this gene.-Clinical significance:...

, CLN5

CLN5

Ceroid-lipofuscinosis neuronal protein 5 is a protein that in humans is encoded by the CLN5 gene.-External links:* -Further reading:...

, and CLN8

CLN8

Protein CLN8 is a protein that in humans is encoded by the CLN8 gene.-Molecular biology:-Clinical:Mutations in this gene are associated with progressive epilepsy with mental retardation , a subtype of neuronal ceroid lipofuscinosis...

. Names for conditions associated with these subtypes include infantile neuronal ceroid lipofuscinosis, Jansky-Bielschowsky disease

Jansky-Bielschowsky disease

Jansky-Bielschowsky disease is a late-infantile form of neuronal ceroid lipofuscinosis associated with a deficiency in tripeptidyl peptidase I....

and northern epilepsy syndrome

Northern epilepsy syndrome

The northern epilepsy syndrome or progressive epilepsy with mental retardation is a subtype of neuronal ceroid lipofuscinosis and a rare disease that is regarded as a Finnish heritage disease. Unlike most Finnish heritage diseases, this syndrome has been reported only in Finland....

. As of 2001, CLN5 and CLN8 had been reported almost exclusively in Finland.

Meckel syndrome

Meckel syndrome

Meckel syndrome is a rare, lethal, ciliopathic, genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations, polydactyly, hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.Meckel-Gruber syndrome is named for Johann...

type 1 (MKS1

MKS1

Meckel syndrome, type 1 also known as MKS1 is a protein that in humans is encoded by the MKS1 gene.- Function :The MKS1 protein along with meckelin are part of the flagellar apparatus basal body proteome and are required for cilium formation....

), a lethal condition, is known in 48 Finnish families.

Other genetic diseases

The European Organization for Rare Diseases

European Organization for Rare Diseases

The European Organization for Rare Diseases is a non-governmental patient-driven alliance of patient organizations and individuals active in the field of rare diseases, that promotes research on rare diseases and commercial development of orphan drugs. EURORDIS is a dedicated to improving the...

(EURORDIS) estimates that there exist between 5,000 and 7,000 distinct rare diseases, affecting between 6% and 8% of the population of the European Union

European Union

The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

. The majority of genetic diseases reported in Finland are not part of the Finnish disease heritage and their prevalence is not higher in Finland than worldwide.

Some genetic diseases are disproportionately rare in Finns. These include cystic fibrosis

Cystic fibrosis

Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

and phenylketonuria

Phenylketonuria

Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...

. In Finland, about 1 in 80 persons are carriers of a cystic fibrosis mutation, compared with an average of 1 in 25 elsewhere in Europe.

Genetic history

Based on molecular data, a population bottleneck

Population bottleneck

A population bottleneck is an evolutionary event in which a significant percentage of a population or species is killed or otherwise prevented from reproducing....

among ancestors of modern Finns is estimated to have occurred about 4000 years ago. This bottleneck resulted in exceptionally low diversity in the Y chromosome

Y chromosome

The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...

, estimated to reflect the survival of just two ancestral male lineages. The distribution of Y chromosome haplotype

Haplotype

A haplotype in genetics is a combination of alleles at adjacent locations on the chromosome that are transmitted together...

s within Finland is consistent with two separate founding settlements, in eastern and western Finland. The population bottleneck is seen only in the Y chromosome. Genetic diversity in autosomal chromosomes and in mitochondrial DNA

Mitochondrial DNA

Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...

(maternally inherited) is as high among Finns as among other European ethnic groups.

The Finnish disease heritage has been attributed to this 4000-year-old bottleneck. However, the geographic distribution and family pedigrees associated with some Finnish heritage disease mutations has linked the enrichment in these mutations to multiple local founder effect

Founder effect

s, some associated with a period of "late settlement" in the 16th century (see History of Finland

History of Finland

The land area that now makes up Finland was settled immediately after the Ice Age, beginning from around 8500 BCE. Most of the region was part of the Kingdom of Sweden from the 13th century to 1809, when it was ceded to the Russian Empire, becoming the autonomous Grand Duchy of Finland. The...

Etymology

Although the concept is older, the English

English language

English is a West Germanic language that arose in the Anglo-Saxon kingdoms of England and spread into what was to become south-east Scotland under the influence of the Anglian medieval kingdom of Northumbria...

term "Finnish disease heritage" appears in the medical literature in the 1990s. One of the earliest uses is in the translated title of a 1994 medical article, soon followed by others.