A Finnish heritage disease is a genetic disease or disorder that is significantly more common in people whose ancestors were ethnic

Finns Finns or Finnish people ( fi, suomalaiset, ) are a Baltic Finnic ethnic group native to Finland. Finns are traditionally divided into smaller regional groups that span several countries adjacent to Finland, both those who are native to these ...

, natives of

Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...

and

Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...

(

Meänmaa (), or sometimes Torne Valley or Torne River Valley ( fi, Tornionlaakso; sv, Tornedalen) lies at the border of Sweden and Finland. It is named after the Torne River flowing through the valley and into the Gulf of Bothnia. Geographically the t ...

) and

Russia Russia (, , ), or the Russian Federation, is a List of transcontinental countries, transcontinental country spanning Eastern Europe and North Asia, Northern Asia. It is the List of countries and dependencies by area, largest country in the ...

(

Karelia Karelia ( Karelian and fi, Karjala, ; rus, Каре́лия, links=y, r=Karélija, p=kɐˈrʲelʲɪjə, historically ''Korjela''; sv, Karelen), the land of the Karelian people, is an area in Northern Europe of historical significance for ...

and

Ingria Ingria is a historical region in what is now northwestern European Russia. It lies along the southeastern shore of the Gulf of Finland, bordered by Lake Ladoga on the Karelian Isthmus in the north and by the River Narva on the border with Est ...

). There are 36

rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discove ...

s regarded as Finnish heritage diseases. The diseases are not restricted to Finns; they are genetic diseases with far wider distribution in the world, but due to

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 ...

s and genetic isolation they are more common in Finns. Within

these diseases are more common in the east and north, consistent with their higher association with ethnic Finns than with ethnic

Swedes Swedes ( sv, svenskar) are a North Germanic ethnic group native to the Nordic region, primarily their nation state of Sweden, who share a common ancestry, culture, history and language. They mostly inhabit Sweden and the other Nordic countr ...

. The Finnish disease heritage does not extend to other ethnic groups in the region, the

Sámi The Sámi ( ; also spelled Sami or Saami) are a Finno-Ugric-speaking people inhabiting the region of Sápmi (formerly known as Lapland), which today encompasses large northern parts of Norway, Sweden, Finland, and of the Murmansk Oblast, Rus ...

and

Karelians Karelians ( krl, karjalaižet, karjalazet, karjalaiset, Finnish: , sv, kareler, karelare, russian: Карелы) are a Finnic ethnic group who are indigenous to the historical region of Karelia, which is today split between Finland and Russi ...

other than Finnish Karelians. It is attributed to a

population bottleneck A population bottleneck or genetic bottleneck is a sharp reduction in the size of a population due to environmental events such as famines, earthquakes, floods, fires, disease, and droughts; or human activities such as specicide, widespread violen ...

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 An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

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 is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...

of many of these diseases have been determined, enabling

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

prenatal testing Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...

, and counseling. This has raised questions of

bioethics Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, med ...

and

eugenics Eugenics ( ; ) is a fringe set of beliefs and practices that aim to improve the genetic quality of a human population. Historically, eugenicists have attempted to alter human gene pools by excluding people and groups judged to be inferior or ...

Finnish heritage disease types

There are 36 identified Finnish heritage diseases: * Amyloidosis, Finnish type *

Lethal arthrogryposis with anterior horn cell disease Lethal arthrogryposis with anterior horn cell disease (LAAHD) is an autosomal recessive genetic disorder characterized by reduced mobility of the foetus and early death. Presentation LAAHD resembles LCCS1 disease but the phenotype is milder, wit ...

Aspartylglucosaminuria Aspartylglucosaminuria (AGU) is an inherited disease that is characterized by a decline in mental functioning, accompanied by an increase in skin, bone and joint issues. The disease is caused by a defect in an enzyme known as aspartylglucosaminida ...

Autoimmune polyendocrinopathy syndrome, type I Autoimmune polyendocrine syndrome type 1 (APS-1), is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome). It causes the dysfunction of multiple endocrine glands due to autoimmunity. It is a genetic disorder, inherite ...

, with or without reversible metaphyseal dysplasia *

Cartilage–hair hypoplasia Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported by Victor McKusick in 1965 ...

Ceroid lipofuscinosis, neuronal Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These l ...

, 1 * Ceroid lipofuscinosis, neuronal, 3 *

, 5 * Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (Synonyms: Northern epilepsy; Epilepsy, progressive, with intellectual disability) *

Choroideremia Choroideremia (; CHM) is a rare, X-linked recessive form of hereditary retinal degeneration that affects roughly 1 in 50,000 males. The disease causes a gradual loss of vision, starting with childhood night blindness, followed by peripheral vision ...

Cohen syndrome Cohen syndrome (also known as Pepper syndrome or Cervenka syndrome) is a very rare autosomal recessive genetic disorder with varied expression, characterised by obesity, intellectual disability, distinct craniofacial abnormalities and potential ocu ...

Cornea plana 2 Cornea plana 2 (CNA2) is a congenital disorder that causes the cornea to flatten and the angle between the sclera and cornea to shrink. This could result in the early development of arcus lipoides, hazy corneal limbus, and hyperopia. There is evid ...

* Diarrhea 1, secretory chloride, congenital *

Diastrophic dysplasia Diastrophic dysplasia is an autosomal recessive dysplasia which affects cartilage and bone development. ("Diastrophism" is a general word referring to a twisting.) Diastrophic dysplasia is due to mutations in the ''SLC26A2'' gene. Affected indivi ...

* Epilepsy, progressive myoclonic 1A ( Unverricht–Lundborg) *

Glycine encephalopathy Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleava ...

(Nonketotic hyperglycinemia) *

GRACILE syndrome GRACILE syndrome is a very rare lethal autosomal recessive genetic disorder, one of the Finnish heritage diseases. GRACILE syndrome has also been found in the UK and Sweden, but not nearly as much as in Finland. It is caused by a mutation in the '' ...

* Gyrate atrophy of choroid and retina *

Hydrolethalus syndrome Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth. HLS is associated with HYLS1 mutations. The gene encoding HYLS1 is responsible for proper ci ...

1 * Infantile-onset spinocerebellar ataxia (

Mitochondrial DNA depletion syndrome Mitochondrial DNA depletion syndrome (MDS or MDDS), or Alper's disease, is any of a group of autosomal recessive disorders that cause a significant drop in mitochondrial DNA in affected tissues. Symptoms can be any combination of myopathic, hepa ...

7) *

Lactase deficiency Lactose intolerance is a common condition caused by a decreased ability to digest lactose, a sugar found in dairy products. Those affected vary in the amount of lactose they can tolerate before symptoms develop. Symptoms may include abdominal pai ...

, congenital * Lethal congenital contracture syndrome 1 * Lysinuric protein intolerance *

Meckel syndrome Meckel may refer to: People German anatomist/physician family Meckel * Johann Friedrich Meckel, the Younger (1781–1833), German anatomist * Johann Friedrich Meckel, the Elder (1724–1774) German anatomist, grandfather of the Younger * Phi ...

Megaloblastic anemia Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA replication, DNA synthesis during red blood cell production. ...

-1, Finnish and Norwegian type *

Mulibrey nanism Mulibrey nanism ("MUscle-LIver-BRain-EYe nanism") is a rare autosomal recessive congenital disorder. It causes severe growth failure along with abnormalities of the heart, muscle, liver, brain and eye. TRIM37 is responsible for various cellular ...

Muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...

-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 * Nephrotic syndrome, type 1 (Finnish congenital nephrosis) * Ovarian dysgenesis 1 *

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy Nasu–Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease characterised by early-onset dementia and multifocal bone cysts. It is caused by autosomal recessive loss of functio ...

(Nasu–Hakola disease) * Progressive encephalopathy with Edema, Hypsarrhythmia and Optic atrophy *

RAPADILINO syndrome RAPADILINO syndrome is an autosomal recessive disorder characterized by: * RA: radial ray defect * PA: patellar aplasia, arched or cleft palate * DI: diarrhea, dislocated joints * LI: little (short stature), limb malformation * NO: slender no ...

Retinoschisis Retinoschisis is an eye disease characterized by the abnormal splitting of the retina's neurosensory layers, usually in the outer plexiform layer. Retinoschisis can be divided into degenerative forms which are very common and almost exclusively i ...

1, X-linked, juvenile * Sialuria, Finnish type (Salla disease) * Tibial muscular dystrophy, tardive *

Usher syndrome Usher syndrome, also known as Hallgren syndrome, Usher–Hallgren syndrome, retinitis pigmentosa–dysacusis syndrome or dystrophia retinae dysacusis syndrome, is a rare genetic disorder caused by a mutation in any one of at least 11 genes result ...

, type 3A Out of these, three are rare causes of

dwarfism Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...

cartilage–hair hypoplasia Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported by Victor McKusick in 1965 ...

diastrophic dysplasia Diastrophic dysplasia is an autosomal recessive dysplasia which affects cartilage and bone development. ("Diastrophism" is a general word referring to a twisting.) Diastrophic dysplasia is due to mutations in the ''SLC26A2'' gene. Affected indivi ...

and

. Four genetically distinct subtypes of

neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These l ...

are found in the Finnish heritage: CLN1,

CLN3 G1/S-specific cyclin Cln3 is a protein that is encoded by the ''CLN3'' gene. The Cln3 protein is a budding yeast G1 cyclin that controls the timing of ''Start'', the point of commitment to a mitotic cell cycle. It is an upstream regulator of t ...

CLN5 Ceroid-lipofuscinosis neuronal protein 5 is a protein that in humans is encoded by the ''CLN5'' gene. The neuronal ceroid lipofuscinoses (CLN or NCL) are a group of autosomal recessive, progressive encephalopathies in children. They are charact ...

, and

CLN8 Protein CLN8 is a protein that in humans is encoded by the ''CLN8'' gene. Molecular biology This gene encodes a transmembrane protein that localizes to the endoplasmic reticulum (ER) and recycles between the ER and the Golgi apparatus via COPII- ...

. page 125 Names for conditions associated with these subtypes include infantile neuronal ceroid lipofuscinosis,

Jansky–Bielschowsky disease Jansky–Bielschowsky disease is an extremely rare autosomal recessive genetic disorder that is part of the neuronal ceroid lipofuscinosis (NCL) family of neurodegenerative disorders. It is caused by the accumulation of lipopigments in the body ...

and

northern epilepsy syndrome Northern epilepsy syndrome (NE), or progressive epilepsy with mental retardation (EPMR), 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 s ...

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

type 1 ( MKS1), a lethal condition, is known in 48 Finnish families.

Other genetic diseases

The

European Organization for Rare Diseases The European Organisation for Rare Diseases (EURORDIS) 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 o ...

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

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

. 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 (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

and

phenylketonuria Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also resu ...

. 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

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 The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...

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

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...

s within Finland is consistent with two separate founding settlements, in eastern and western Finland. The Finnish disease heritage has been attributed to this 4000-year-old bottleneck. The geographic distribution and family pedigrees associated with some Finnish heritage disease mutations has linked the enrichment in these mutations to multiple local

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

History of Finland The history of Finland begins around 9,000 BC during the end of the last glacial period. Stone Age cultures were Kunda, Comb Ceramic, Corded Ware, Kiukainen, and . The Finnish Bronze Age started in approximately 1,500 BC and the Iron Age star ...

Etymology

Although the concept is older, the

English English usually refers to: * English language * English people English may also refer to: Peoples, culture, and language * ''English'', an adjective for something of, from, or related to England ** English national ide ...

term "Finnish disease heritage" first 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.

References

{{DEFAULTSORT:Finnish Heritage Disease Rare diseases Autosomal recessive disorders Health in Finland

Finnish heritage disease types

Other genetic diseases

Genetic history

Etymology

See also

References