Finnish heritage disease

A Finnish heritage disease is a genetic disease or disorder that is significantly more common in people whose ancestors were ethnic Finns, natives of Finland and Sweden (Meänmaa) and Russia (Karelia and Ingria). About 40 rare diseases are regarded as Finnish heritage diseases.^[1] The diseases are not restricted to Finns; they are genetic diseases with far wider distribution in the world, but due to founder effects and genetic isolation they are more common in Finns.

Within Finland these diseases are more common in the east and north, consistent with their higher association with ethnic Finns than with ethnic Swedes.^[2] The Finnish disease heritage does not extend to other ethnic groups in the region, the Sámi and Karelians other than Finnish Karelians. It is attributed to a population bottleneck among ancestors of modern Finns, estimated to have occurred about 4000 years ago, presumably when populations practicing agriculture and animal husbandry arrived in Finland.^[3]

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.^[4] Most of the gene defects are autosomal recessives, 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 of many of these diseases have been determined, enabling genetic testing, prenatal testing, and counseling. This has raised questions of bioethics and eugenics.^[5]

Finnish heritage disease

Finnish heritage diseases include:

• APECED (autoimmune polyendocrinopathy—candidiasis—ectodermal dystrophy)
• Aspartylglucosaminuria, a lysosomal storage disease
• Congenital adrenal hyperplasia^[6]
• Congenital nephrotic syndrome,^[7] a kidney disease of newborn babies
• Congenital chloride diarrhea
• Congenital stromal corneal dystrophy
• GRACILE syndrome
• Lethal arthrogryposis with anterior horn cell disease
• Lethal congenital contracture syndrome 1
• Meretoja syndrome
• Meckel syndrome
• Myotonia congenita
• Nonketotic hyperglycinemia
• Salla disease,^[8] a lysosomal storage disease
• PEHO syndrome
• Rapadilino syndrome
• Retinoschisis
• Usher syndrome

Three rare causes of dwarfism are included in the Finnish heritage: cartilage-hair hypoplasia, diastrophic dysplasia and Mulibrey nanism.

Four genetically distinct subtypes of neuronal ceroid lipofuscinosis are found in the Finnish heritage: CLN1, CLN3, CLN5, and CLN8.^[9] Names for conditions associated with these subtypes include infantile neuronal ceroid lipofuscinosis, Jansky-Bielschowsky disease and northern epilepsy syndrome. As of 2001, CLN5 and CLN8 had been reported almost exclusively in Finland.^[9]

Meckel syndrome type 1 (MKS1^[10]), a lethal condition, is known in 48 Finnish families.^[11]

Other genetic diseases

The European Organization for Rare Diseases (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.^[12] 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 and phenylketonuria. 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.^[13]

Genetic history

Based on molecular data, a population bottleneck among ancestors of modern Finns is estimated to have occurred about 4000 years ago.^[3] This bottleneck resulted in exceptionally low diversity in the Y chromosome, estimated to reflect the survival of just two ancestral male lineages.^[14][15] The distribution of Y chromosome haplotypes within Finland is consistent with two separate founding settlements, in eastern and western Finland.^[16] The population bottleneck is seen only in the Y chromosome. Genetic diversity in autosomal chromosomes and in mitochondrial DNA (maternally inherited) is as high among Finns as among other European ethnic groups.^[16]

The Finnish disease heritage has been attributed to this 4000-year-old bottleneck.^[3] The geographic distribution and family pedigrees associated with some Finnish heritage disease mutations has linked the enrichment in these mutations to multiple local founder effects, some associated with a period of "late settlement" in the 16th century (see History of Finland).^[17]

Etymology

Although the concept is older, the English 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,^[18] soon followed by others.^[3][19]

See also

• Leena Palotie
• Nine diseases
• Population genetics
• BCG disease outbreak in Finland in the 2000s
• Medical genetics of Ashkenazi Jews
• FAIDD (The Finnish Association on Intellectual and Developmental Disabilities)
• Finno-Ugrian suicide hypothesis

References