Overview
Constitutional mismatch repair deficiency (CMMRD) syndrome, also known as biallelic mismatch repair deficiency (BMMRD), is a rare and severe cancer predisposition syndrome caused by biallelic (homozygous or compound heterozygous) germline mutations in one of the four mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. Unlike Lynch syndrome, where a single defective copy of an MMR gene is inherited, individuals with CMMRD carry mutations in both copies, leading to a dramatically elevated and early-onset cancer risk. The condition follows an autosomal recessive inheritance pattern. CMMRD affects multiple body systems. The hallmark features include childhood-onset malignancies, particularly hematological cancers (such as T-cell lymphomas and acute leukemias), brain tumors (most commonly high-grade gliomas), and gastrointestinal cancers (including colorectal and small bowel cancers), often occurring in the first or second decade of life. Many patients develop multiple primary cancers over their lifetime. In addition to cancer predisposition, affected individuals frequently display features reminiscent of neurofibromatosis type 1 (NF1), including café-au-lait macules and, less commonly, other skin findings, which can lead to initial misdiagnosis. Some patients may also exhibit signs of immunodeficiency, which is reflected in the ICD-10 classification under D80.8. Diagnosis is established through genetic testing of the MMR genes, microsatellite instability analysis, and immunohistochemistry of tumor tissue. Functional assays and the presence of characteristic clinical features support the diagnosis. Treatment involves cancer-directed therapy tailored to the specific malignancy, including surgery, chemotherapy, and radiation, though tumors in CMMRD may respond differently to standard protocols. Surveillance protocols with frequent and comprehensive cancer screening beginning in early childhood are critical for early detection. Emerging evidence suggests that immune checkpoint inhibitors may be effective in hypermutated CMMRD-associated tumors due to their high tumor mutational burden. Genetic counseling is essential for affected families.
Also known as:
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Childhood
Begins in childhood, roughly ages 1 to 12
FDA & Trial Timeline
10 eventsWomen's Hospital School Of Medicine Zhejiang University — PHASE2
Shanghai Zhongshan Hospital — PHASE2
Emory University — PHASE2
Cambridge University Hospitals NHS Foundation Trust — PHASE2
San Raffaele University
Peking Union Medical College Hospital — NA
Novartis Pharmaceuticals — PHASE1
Yu jiren — PHASE2
Alexander B Olawaiye, MD — PHASE1, PHASE2
Assistance Publique - Hôpitaux de Paris — NA
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
1 availableIMFINZI
in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair …
in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test
Rare Disease Specialist
Rare Disease Specialist
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Financial Resources
2 resourcesYervoy
Bristol-Myers Squibb Company
Yervoy Patient Support (BMS Access Support)
Travel Grants
No travel grants are currently matched to Constitutional mismatch repair deficiency syndrome.
Community
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Start the conversation →Latest news about Constitutional mismatch repair deficiency syndrome
Disease timeline:
New recruiting trial: Immunotherapy (Toripalimab) for Reducing Recurrence Risk After Surgery for Mismatch Repair Deficient Stage IIB, IIC, or III Colon Cancer
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: Perioperative Chemotherapy Plus Toripalimab for dMMR Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: Neoadjuvant Immunotherapy for T4 dMMR Colon Cancer
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: Immune Checkpoint Inhibitors for Organ Preservation in Non-metastatic dMMR/MSI-H Gastric or Colon Cancers
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
New recruiting trial: T-regulatory Cell Depletion with E7777 Combined with Pembrolizumab in Recurrent or Metastatic Solid Tumors
A new clinical trial is recruiting patients for Constitutional mismatch repair deficiency syndrome
Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Common questions about Constitutional mismatch repair deficiency syndrome
What is Constitutional mismatch repair deficiency syndrome?
Constitutional mismatch repair deficiency (CMMRD) syndrome, also known as biallelic mismatch repair deficiency (BMMRD), is a rare and severe cancer predisposition syndrome caused by biallelic (homozygous or compound heterozygous) germline mutations in one of the four mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. Unlike Lynch syndrome, where a single defective copy of an MMR gene is inherited, individuals with CMMRD carry mutations in both copies, leading to a dramatically elevated and early-onset cancer risk. The condition follows an autosomal recessive inheritance pattern. CMMRD af
How is Constitutional mismatch repair deficiency syndrome inherited?
Constitutional mismatch repair deficiency syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Constitutional mismatch repair deficiency syndrome typically begin?
Typical onset of Constitutional mismatch repair deficiency syndrome is childhood. Age of onset can vary across affected individuals.
Are there clinical trials for Constitutional mismatch repair deficiency syndrome?
Yes — 5 recruiting clinical trials are currently listed for Constitutional mismatch repair deficiency syndrome on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat Constitutional mismatch repair deficiency syndrome?
25 specialists and care centers treating Constitutional mismatch repair deficiency syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.
What treatment and support options exist for Constitutional mismatch repair deficiency syndrome?
1 patient support program are currently tracked on UniteRare for Constitutional mismatch repair deficiency syndrome. See the treatments and support programs sections for copay assistance, eligibility, and contact details.