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Genetic Disorders Associated With Ashkenazi Jewish Ancestry. ARUP Consult®. Retrieved October 10, 2026, https://arupconsult.com/content/ashkenazi-jewish-genetic-diseases

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Genetic Disorders Associated With Ashkenazi Jewish Ancestry

Last Literature Review: June 2026 Last Update:

Medical Experts

Contributor
Contributor
Contributor

Mao

Rong Mao, MD, FACMG
Rong Mao, MD, FACMG
Professor and Co-Director of Laboratory Genetics and Genomics Fellowship, University of Utah
Medical Director, Molecular Genetics and Genomics, ARUP Laboratories

Certain autosomal recessive genetic disorders have a higher prevalence in individuals of Ashkenazi Jewish descent. These disorders include cystic fibrosis, Canavan disease, familial dysautonomia, Tay-Sachs disease, Fanconi anemia, Niemann-Pick disease, Bloom syndrome, mucolipidosis IV, and Gaucher disease, among others. , ,  Due to the increased incidence of these disorders in this population, routine preconception or prenatal expanded carrier screening is recommended. ,  Laboratory testing may entail a gene panel for multiple disorders, single-disorder genetic testing, or other testing (e.g., hexosaminidase enzyme [HexA] assays for Tay-Sachs disease), depending on the needs of the patient. , ,  Genetic carrier testing may involve ethnic-specific, pan-ethnic, or expanded carrier screening.

Quick Answers for Clinicians

For which genetic disorders is a patient of Ashkenazi Jewish descent commonly screened during pregnancy or if planning a pregnancy?

Individuals of Ashkenazi Jewish descent may carry pathogenic variants for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, familial hyperinsulinism, Fanconi anemia C, Gaucher disease, glycogen storage disease type 1a, Joubert syndrome type 2, maple syrup urine disease type 1B, mucolipidosis IV, Niemann-Pick disease type A, and Tay-Sachs disease, among other disorders.  Guidelines from the American College of Obstetricians and Gynecologists (ACOG) recommend offering expanded carrier testing for disorders with a carrier frequency of 1 in 100 or greater that have a significant negative impact on quality of life (among other criteria) to individuals of Ashkenazi Jewish descent who are pregnant or plan to become pregnant. , 

Are there other individuals who should be tested for diseases commonly associated with Ashkenazi Jewish ancestry?

Individuals of French-Canadian and Louisiana Cajun ancestry are at increased risk for Tay-Sachs disease. Testing for hexosaminidase A (HexA) is recommended in these individuals. ,  Individuals of Japanese, Saudi, and certain Mennonite populations are at increased risk for Fanconi anemia, group C.  Founder variants have been identified for various ethnic groups for which carrier screening may be available.  The American College of Medical Genetics and Genomics (ACMG) now recommends offering tiered carrier screening universally for a large panel of genes, including those commonly implicated in genetic disorders common in the Ashkenazi Jewish population, to all individuals in the preconception or prenatal period. 

Which laboratory tests are recommended for Tay-Sachs disease?

Ethnicity-based carrier screening for individuals of Ashkenazi Jewish descent is widely available. Genetic testing for Tay-Sachs disease is appropriate as part of an expanded carrier screening panel for individuals of Ashkenazi Jewish descent, or if either member of a couple is of Ashkenazi Jewish descent.  Hexosaminidase A (HexA) testing (serum or leukocyte) may be used for screening in individuals of Ashkenazi Jewish background. ,  False-positive results may occur in serum enzyme testing in pregnant individuals or those taking oral contraceptives; in these patient populations, leukocyte testing must be performed. 

Indications for Testing

Laboratory testing for genetic disorders associated with Ashkenazi Jewish ancestry is used for expanded carrier screening in individuals of Ashkenazi Jewish descent who are planning a pregnancy or are currently pregnant ,  and for disorder-specific testing in the following circumstances:

  • Screening in relatives of individuals with an identified pathogenic variant included on the panel , , 
  • Diagnosis in individuals of Ashkenazi Jewish descent with suggestive symptoms , 
  • Targeted genetic sequencing in individuals of non-Ashkenazi Jewish descent who are reproductive partners of individuals with an identified pathogenic variant , , 

Laboratory Testing

Screening

Carrier Screening

For individuals of Ashkenazi Jewish ancestry, the American College of Obstetricians and Gynecologists (ACOG) recommends testing for nine disorders and considering testing for five additional diseases that have increased frequency in individuals of Ashkenazi Jewish descent.  The American College of Medical Genetics and Genomics (ACMG) now recommends offering tiered carrier screening, regardless of ancestry, for a large panel of genes (including those implicated in genetic disorders common in the Ashkenazi Jewish population) to all individuals in the preconception or prenatal period.  A central tenet of this update is the increased genetic admixture among populations today, and the resulting recommendation is that carrier screening should be available to diverse populations, regardless of ethnic background.  In addition, molecular testing methodologies have drastically improved throughput and cost of testing.  Testing before pregnancy is recommended to enable individuals to make fully informed reproductive decisions. , 

Conditions for Which Screening Is Recommended in Those of Ashkenazi Jewish Ancestry
Diseases Recommended for Carrier Screening by ACOG and ACMGa
Disease (Gene)Carrier Frequency Among Ashkenazi Jewish Individuals in the U.S.Symptoms and Characteristics
Bloom syndrome (BLM)1/100Pre- and postnatal growth deficiency; skin lesions that appear at 1-2 yrs of age; benign and malignant tumors in childhood; telangiectatic hypo- and hyperpigmented skin lesions; male infertility; decreased life expectancy due to malignancy
Canavan disease (ASPA)1/40-1/82Macrocephaly; loss of motor control beginning at 3-5 mos of age; failure to sit, stand, or ambulate; survival usually until childhood or teenage yrs
Cystic fibrosis (CFTR) Refer to the ARUP Consult Cystic Fibrosis topic
Familial dysautonomia (IKBKAP)1/36Delayed motor milestones in infants and progressive deterioration of gait throughout life; gastrointestinal dysfunction with emesis; altered sensitivity to pain and temperature; cardiovascular instability; decreased life expectancy
Fanconi anemia group C (FANCC)1/93Progressive bone marrow failure during first decade of life; increased risk of malignancy above that of the general population; developmental delays; physical malformations that may include short stature, abnormal skin pigmentation, or malformations of the eyes, ears, heart, forearms, thumbs, kidneys; survival varies
Gaucher disease (GBA1)1/18

Type 1 (most prevalent type among individuals of Ashkenazi Jewish descent): bone disease; hepatosplenomegaly; anemia, thrombocytopenia; lung disease; no primary CNS disease

Type 2: CNS degeneration by 2 yrs of age with a rapidly progressive course; survival until 4 yrs of age

Type 3: slowly progressive CNS degeneration; survival until 20s or 30s

Mucolipidosis IV (MCOLN1)1/100-1/127Severe psychomotor delay; progressive visual impairment due to retinal degeneration and corneal clouding; progressive neurodegeneration is typical; variable life expectancy (most individuals live into adulthood)
Niemann-Pick disease type A (SMPD1)1/80-1/100Hepatosplenomegaly by 3 mos of age; developmental delay and severe neurodegeneration; progressive hypotonia and rigidity; cherry-red spot on the macula of the retina; survival until 3-5 yrs of age
Tay-Sachs disease (HEXA)1/27

Classic phenotype: progressive loss of motor skills beginning at 3-6 mos of age; progressive neurodegeneration resulting in blindness, seizures, and eventually, total incapacitation; survival until 4-6 yrs of age

Subacute juvenile: symptom onset after 2 yrs of age; abnormal gait, dysarthria, cognitive decline, developmental regression; survival until second decade

Late onset: symptom onset in teen/young adult yrs; slower disease progression; variable neurologic findings, including progressive dystonia, spinocerebellar degeneration, motor neuron disease, and psychiatric symptoms

Diseases Recommended for Consideration for Carrier Screening by ACOG
ABCC8-related hyperinsulinism (ABCC8)1/52Neonatal onset; hypoglycemia that varies from mild to severe; normal lifespan with proper management
Glycogen storage disease type 1a (G6PC1)1/71Hepatomegaly; growth delay/short stature; hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia; additional long-term complications include osteoporosis, delayed puberty, renal disease, systemic hypertension, hepatic adenomas with potential for malignant transformation; survival into adulthood with treatment
Joubert syndrome type 2 (TMEM216)1/92-1/100“Molar tooth sign” cerebellar and brain stem malformation; hypotonia; developmental delay/intellectual disability; normal lifespan (typically), but minority may have shortened lifespan depending on severity
Maple syrup urine disease type 1B (BCKDHB)1/113Maple syrup odor in urine; classically, presentation within first few days of life with irritability, poor feeding and lethargy, intermittent apnea; progression to coma and death within 7-10 days if untreated
Usher syndrome type 1F (PCDH15)1/27-1/238Profound congenital bilateral sensorineural hearing loss; adolescent-onset retinitis pigmentosa; loss of vestibular function
Usher syndrome type 3A (CLRN1)1/120Postlingual, progressive hearing loss; late-onset progressive loss of vision due to retinitis pigmentosa; variable loss of vestibular function
Additional Diseases Common in Individuals of Ashkenazi Jewish Descent
Dihydrolipoamide dehydrogenase deficiency (DLD)1/94-1/110

Early-onset disease: presentation in infancy with hypotonia and lactic acidosis with progressive encephalopathy; survival usually until 1-2 yrs of age, typically with neurologic deficits

Primarily hepatic disease: variable onset from infancy to 4th decade of life; liver injury/failure, usually preceded by nausea/vomiting; typically, normal intellect with no neurologic findings; variable lifespan depending on severity of condition

Myopathic presentation: rare

NEB-related nemaline myopathy (NEB)1/108Presentation in first year of life with static or slowly progressive muscle weakness of the face, neck, arms, and legs; hypotonia; feeding difficulties; typically, normal lifespan and active independent life

CNS, central nervous system

aThese disorders show significantly higher frequency in the Ashkenazi Jewish population than in the general population.

Sources: ACOG, 2017 ; Gregg, 2021 ; Mehta, 2026 ; GeneReviews , , , , , , , , , , , , 

Disorder-Specific Screening

Tay-Sachs Disease

Tay-Sachs testing is recommended for individuals of Ashkenazi Jewish, French-Canadian, or Cajun descent, as well as reproductive partners of an individual with an identified Tay-Sachs pathogenic variant and individuals with a family history of Tay-Sachs disease. ,  Identification of the familial variant is recommended before testing to ensure it is detectable by the testing selected. For women who are pregnant or taking oral contraceptives, HexA enzyme testing must be performed in leukocytes, given that false-positive results may occur when using a serum test for these patients.  Molecular testing of the HEXA gene can be considered to identify pathogenic variants when HexA enzyme activity is abnormal.

Cystic Fibrosis

Individuals of Ashkenazi Jewish descent are at increased risk for cystic fibrosis. Cystic fibrosis carrier screening should be offered to women of all ethnicities who are pregnant or planning to become pregnant. , ,  Refer to the ARUP Consult Cystic Fibrosis topic for more information about appropriate laboratory testing.

Other Ashkenazi Jewish Genetic Disorders

Carrier screening is recommended for non-Ashkenazi Jewish individuals whose reproductive partner is a carrier of one or more disorders or in individuals with a family history of a particular disorder when the familial pathogenic variant is unknown. ,  Disorder-specific testing may be ordered in these circumstances; however, the detection rate of the Ashkenazi Jewish common variant panels varies by disorder, and the detection rate is largely unknown for other populations. 

Diagnosis

The selection of appropriate testing for genetic diseases associated with Ashkenazi Jewish ancestry depends on the specific disease that is suspected (refer to the Conditions for Which Screening Is Recommended in Those of Ashkenazi Jewish Ancestry table).

Tay-Sachs Disease

HexA enzymatic testing is the initial test to confirm a diagnosis of Tay-Sachs disease in a symptomatic individual. Molecular testing of the HEXA gene can be used to identify pathogenic variants when HexA enzyme activity is abnormal. Molecular genetic testing is also necessary to distinguish pseudodeficiency alleles from pathogenic variants.

Cystic Fibrosis

Diagnostic testing for cystic fibrosis includes sweat chloride and genetic testing (refer to the ARUP Consult Cystic Fibrosis topic for additional information).

Other Ashkenazi Jewish Genetic Diseases

Genetic testing for diagnostic purposes for many Ashkenazi Jewish disorders typically includes full sequencing of the associated gene. Alternatively, an Ashkenazi Jewish common variant panel can be used in individuals of Ashkenazi Jewish descent or with a family history of a pathogenic variant that is present on the panel. Additionally, if both expectant parents are identified as carriers of a specific disorder, fetal targeted sequencing for the familial pathogenic variants can be used as follow-up testing. Targeted sequencing can also be used for postnatal diagnosis of a specific disorder.

ARUP Laboratory Tests

Panel Test

Disorder-Specific Tests

Tests for Tay-Sachs Disease
Test for Cystic Fibrosis
Tests for Other Ashkenazi Jewish Genetic Diseases
Targeted Tests for Familial Pathogenic Variants

References