Hereditary Blood Cancers

What You Should Know About ANKRD26-Related Thrombocytopenia

Individuals with an inherited pathogenic/likely pathogenic (P/LP) variant in the ANKRD26 gene are at increased risk of having low platelet levels (thrombocytopenia) and blood cancers such as leukemia or myelodysplastic syndrome (MDS).

Risks Associated with ANKRD26-Related Thrombocytopenia

Thrombocytopenia can cause bleeding tendencies such as easy bruising and slow blood clotting. Around 5-8% of individuals with the ANKRD26 gene develop blood cancers, such as acute myeloid leukemia (AML), MDS, or chronic myeloid leukemia (CML).

Managing the Risks

UT Southwestern’s Cancer Genetics and Blood Cancers programs help people receive appropriate cancer surveillance and management based on their genetic test results. For more information about our clinics or to request an appointment, please call us at 214-645-2563.

Bleeding Tendencies & Blood Cancers

• Our hematology-oncologists work with patients to determine appropriate surveillance and management.
• These specialists can discuss measuring platelet counts for thrombocytopenia and appropriate recommendations for follow-up based on counts and personal bleeding tendencies.
• Specialists can also discuss appropriate recommendations for monitoring blood and bone marrow for blood cancers, as needed.

Risk to Family Members

P/LP variants in the ANKRD26 gene are inherited in an autosomal dominant manner. This means that children, brothers, sisters, and parents of individuals with an ANKRD26 P/LP variant have a 1 in 2 (50%) chance of having the P/LP variant. Both males and females can inherit a familial ANKRD26 P/LP variant and pass it on to their children.

What You Should Know About DDX41-Associated Familial MDS and AML

Individuals with an inherited pathogenic/likely pathogenic (P/LP) variant in the DDX41 gene are at increased risk of developing certain adult-onset hematologic malignancies

Risks Associated with DDX41-Associated Familial MDS and AML

Individuals with a DDX41 P/LP variant have a 20-30% lifetime risk of developing blood cancers such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The average age of onset of MDS for individuals with a DDX41 P/LP variant is 65 years old.

Managing the Risks

UT Southwestern’s Cancer Genetics and Blood Cancers programs help people receive appropriate cancer surveillance and management based on their genetic test results. For more information about the clinic or to request an appointment, please call us at 214-645-2563.

Blood Cancers & Other Features

• Our hematology-oncologists work with patients to determine appropriate surveillance and management.
• These specialists can discuss appropriate recommendations for monitoring blood and bone marrow for blood cancers, as needed.

Risk to Family Members

P/LP variants in the DDX41 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a DDX41 P/LP variant have a 1 in 2 (50%) chance of having the P/LP variant. Both males and females can inherit a familial DDX41 P/LP variant and pass it on to their children.

What You Should Know About ETV6 Thrombocytopenia and Predisposition to Leukemia

Individuals with an inherited pathogenic/likely pathogenic (P/LP) variant in the ETV6 gene are at an increased risk of developing low platelets and blood cancers.

Risks Associated with ETV6 Thrombocytopenia and Predisposition to Leukemia

Thrombocytopenia (low platelets) affects 90% of individuals with an ETV6 P/LP variant. About 20%-30% of individuals with an ETV6 P/LP variant develop various blood cancers such as B-cell acute lymphoblastic leukemia, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS).

Managing the Risks

UT Southwestern’s Cancer Genetics and Blood Cancers programs help people receive appropriate cancer surveillance and management based on their genetic test results. For more information about our clinics or to request an appointment, please call us at 214-645-2563.

Blood Cancers & Other Features

• Our hematology-oncologists work with patients to determine appropriate surveillance and management.
• These specialists can discuss measuring platelet counts for thrombocytopenia and appropriate recommendations for follow-up based on counts and personal bleeding tendencies.
• Specialists can also discuss appropriate recommendations for monitoring blood and bone marrow for blood cancers, as needed.

Risk to Family Members

P/LP variants in the ETV6 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an ETV6 P/LP variant have a 1 in 2 (50%) chance of having the P/LP variant. Both males and females can inherit a familial ETV6 P/LP variant and pass it on to their children.

What You Should Know About Fanconi Anemia

Fanconi anemia (FA) causes an error in blood cell growth from the bone marrow, leading to a low number of blood cells. Individuals with this condition face an elevated risk of developing various blood cancers. This disease is caused by pathogenic/likely pathogenic (P/LP) variants in the following genes: BRCA1, BRCA2, BRIP1, ERCC4, FAAP100, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, and XRCC2.

Risks Associated with Fanconi Anemia

Individuals with Fanconi anemia (FA) have an increased risk of bone marrow failure, leukemia, and other cancers, particularly squamous cell carcinomas of the head, neck, esophagus, skin, and gynecological organs. Because it is a variable condition, individuals with Fanconi anemia may also have features such as birth defects of the limbs, ears, digestive tract, and reproductive tract, as well as short stature, oral diseases, and skin conditions. Individuals may have any combination of these features, which can vary widely even within families.

Managing the Risks

UT Southwestern’s Cancer Genetics and Blood Cancers programs help people receive appropriate cancer surveillance and management based on their genetic test results. For more information about our clinic or to request an appointment, please call us at 214-645-2563.

Blood Cancers & Other Features

• Our hematology-oncologists work with patients to determine appropriate surveillance and risk management.
• These specialists can discuss appropriate recommendations for monitoring blood and bone marrow.

Oncology

• Our oncology specialists also work with patients to determine appropriate surveillance and risk management for other cancer risks associated with Fanconi anemia.

Other Features

• Our endocrinologists, gynecologists, audiologists, otolaryngologists, gastroenterologists, and orthopedic specialists can also help assess and manage other features of Fanconi anemia.

Risk to Family Members

Fanconi anemia can be inherited in autosomal recessive, autosomal dominant, or X‑linked patterns. Children, siblings, and parents of an affected individual may also be at risk of having the familial P/LP variant(s). Both males and females can inherit P/LP variants associated with Fanconi anemia and can pass them on to their children.

What You Should Know About GATA2 Deficiency

GATA2 deficiency is caused by a pathogenic/likely pathogenic (P/LP) variant in the GATA2 gene. This can lead to a weakened immune system, bone marrow failure (low number or poorly formed blood cells), and an increased risk of developing blood cancers.

Risks Associated with GATA2 Deficiency

The lifetime risk for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with a GATA2 P/LP variant is around 70%, with an average onset age of 29 years. Individuals with a P/LP variant in the GATA2 gene may also have a higher risk of infections caused by viruses, bacteria, or fungi. Some individuals may also have deafness and/or chronic lymphedema (buildup of fluid in arms and/or legs).

Managing the Risks

UT Southwestern’s Cancer Genetics Program helps people receive appropriate cancer surveillance and management based on their genetic test results. For more information about the clinic or to request an appointment, please call us at 214-645-2563.

Blood Cancers & Other Features

• Our hematology-oncologists work with patients to determine appropriate surveillance and risk management.
• These specialists can discuss appropriate recommendations for monitoring blood in patients with hematological malignancies and for treating blood cancers, as needed.  They can also monitor and treat other features of GATA2 deficiency.

Risk to Family Members

GATA2 deficiency is inherited in an autosomal dominant manner. This means that children, brothers, sisters, and parents of individuals with a GATA2 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial GATA2 P/LP variant and can pass it on to their children.

What You Should Know About MANS

MANS occurs when pathogenic or likely pathogenic (P/LP) variants are found in both copies of the MBD4 gene. Individuals with MANS are at an increased risk of developing blood cancers, colon polyps, colon cancer, and melanoma of the eye.

Risks Associated with MANS

Individuals with MANS have an increased risk of developing early‑onset acute myeloid leukemia (AML). It also increases the risk for uveal, melanoma, and colon polyps (15-100+ adenomas) and colorectal cancer. Schwannomas have also been reported in individuals with MANS.

Managing the Risks

UT Southwestern’s Cancer Genetics Program helps people receive appropriate cancer surveillance and management based on their genetic test results. For more information about the clinic or to request an appointment, please call us at 214-645-2563.

Blood Cancers

• Our hematology-oncologists work with patients to determine appropriate surveillance and risk management.
• These specialists can also discuss appropriate recommendations for monitoring blood in patients with hematological malignancies and for treating blood cancers, as needed.

Ophthalmology

• Our ophthalmologists work with diagnosed patients to begin annual ophthalmologic exams.

Gastroenterology

• Our gastroenterologists work with patients to determine appropriate colonoscopy surveillance and risk management.

Risk to Family Members

MANS is inherited in an autosomal recessive manner. This means that an individual must inherit two P/LP variants, one from each parent, to be affected. Parents of an individual with MANS are typically carriers, and each sibling of an affected individual has a 1 in 4 (25%) chance of having the condition, a 1 in 2 (50%) chance of being a carrier, and a 1 in 4 (25%) chance of having neither variant. Both males and females can inherit MBD4 P/LP variants and can pass on a variant to their children.

What You Should Know About RUNX1 Familial Platelet Disorder

Individuals with an inherited pathogenic or likely pathogenic (P/LP) variant in the RUNX1 gene are at an increased risk of having low platelet levels (thrombocytopenia) and blood cancers such as myelodysplastic syndrome (MDS) or leukemia.

Risks Associated with RUNX1 Familial Platelet Disorder

About 90% of people with an inherited P/LP variant in the RUNX1 gene develop thrombocytopenia, which can cause bleeding tendencies such as easy bruising and slow blood clotting. The severity of bleeding tendencies varies based on platelet levels. Around 20-50% of individuals with an inherited P/LP variant in the RUNX1 gene develop MDS or acute myeloid leukemia (AML). Lymphoid malignancies have also been seen in individuals with RUNX1 familial platelet disorder. Additionally, skin findings such as eczema and psoriasis have been reported in about half of families with the disorder.

Managing the Risks

UT Southwestern’s Cancer Genetics Program helps people receive appropriate cancer surveillance and management based on their genetic testing results. For more information about the clinic or to request an appointment, please call us at 214-645-2563.

Thrombocytopenia & Blood Cancers

• Our hematology-oncologists work with patients to determine appropriate surveillance and risk management.
• These specialists can discuss measuring platelet counts for thrombocytopenia as well as appropriate recommendations for follow-up based on counts and personal bleeding tendencies.
• They can also discuss appropriate recommendations for monitoring the blood for hematological malignancies and treatment for blood cancers, as needed.

Skin Findings

• Our dermatologists work with patients to determine appropriate surveillance and management recommendations.
• These specialists can perform a skin exam and discuss treatment for skin findings such as eczema or psoriasis.

Risk to Family Members

P/LP variants in the RUNX1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a RUNX1 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial RUNX1 P/LP variant and can pass it on to their children.

What You Should Know About Short Telomere Syndromes

Short telomere biology disorder, also known as dyskeratosis congenita, is caused by mutations in the following genes: ACD, CTC1, DKC1, NAF1, NHP2, NOP10, PARN, POT1, RPA1, RTEL1, STN1, TERC, TERT, TINF2, WRAP53, and ZCCHC8. Individuals with this condition have short telomeres (protective caps at the end of genetic material) and are at risk for low blood cell counts, lower quality blood cells, blood cancers, pulmonary fibrosis, and various head and neck cancers.

Risks Associated with Short Telomere Syndromes

Individuals with short telomere syndromes are at an increased risk for bone marrow failure and blood cancer such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). There is also an increased risk for certain solid tumors, particularly squamous cell cancers of the head and neck or anogenital region. Additional health concerns may involve skin and nail changes, eye differences, dental issues, pulmonary fibrosis, liver disease, differences in blood vessel and heart growth, gastrointestinal or urinary tract narrowing, and skeletal problems such as short stature, osteoporosis (fragile bones), or avascular necrosis (death of bone tissue from lack of blood supply. Related conditions, such as Hoyeraal Hreidarsson syndrome and Revesz syndrome, can include developmental delays and neurological or retinal abnormalities.

Managing the Risks

UT Southwestern’s Cancer Genetics Program helps people receive appropriate cancer surveillance and management based on their genetic test results. For more information about the clinic or to request an appointment, please call us at 214-645-2563.

Blood Cancers

• Our hematology-oncologists work with patients to determine appropriate surveillance and risk management.
• These specialists discuss appropriate recommendations for monitoring blood in patients with hematological malignancies and for treating blood cancers, as needed.

Ophthalmology

• Our ophthalmologists provide comprehensive eye exams for every stage of care.

Immunology

• Our immunologists work with patients to evaluate immune function and guide vaccination and follow‑up based on immunodeficiency risk.

Dermatology

• Our dermatologists work with patients to perform skin exams.

Risk to Family Members

Short telomere syndromes can be inherited in autosomal recessive, autosomal dominant, or X‑linked patterns. Children, siblings, and parents of an affected individual may also be at risk of having the familial P/LP variant(s). Both males and females can inherit P/LP variants associated with short telomere syndromes and can pass them on to their children.

What You Should Know About Wiskott- Aldrich Syndrome

Wiskott-Aldrich syndrome is a genetic disorder of the immune system caused by a pathogenic/likely pathogenic (P/LP) variant in the WAS gene. This syndrome is associated with abnormal immune function, eczema, and a lowered ability to form blood clots. It is also known to cause individuals to be at risk for developing blood cancers.

Risks Associated with Wiskott- Aldrich Syndrome

Individuals with Wiskott-Aldrich Syndrome experience various symptoms such as eczema and thrombocytopenia, which causes easy bleeding and bruising. Individuals are also at a risk for higher susceptibility for infections, autoimmune disorders, and blood cancers such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Managing the Risks

UT Southwestern’s Cancer Genetics Program helps people receive appropriate cancer surveillance and management based on their genetic test results. For more information about the clinic or to request an appointment, please call us at 214-645-2563.

Thrombocytopenia & Blood Cancers

• Our hematology-oncologists work with patients to determine appropriate surveillance and risk management.
• These specialists can also discuss appropriate recommendations for monitoring blood in patients with hematological malignancies and for treating blood cancers, as needed.

Dermatology

• Our dermatologists can perform a skin exam and discuss treatment for skin findings such as eczema or psoriasis.

Risk to Family Members

WAS P/LP variants are inherited in an X-linked manner. This means individuals with one X chromosome with a WAS P/LP variant have the syndrome, while individuals with two X chromosomes with a WAS P/LP variant are carriers. Individuals with two X chromosomes are not expected to have the primary features of these conditions but may have subtle features. Family members of individuals with a WAS P/LP variant also have a chance to have a WAS mutation that can be passed on to children.