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Database-guided Flow-cytometry for Evaluation of Bone Marrow Myeloid Cell Maturation
Published on: November 3, 2018
Inherited bone marrow failure syndromes: phenotype as a tool for early diagnostic suspicion at a major reference
Paula Leal-Anaya1,2,3, Tamara N Kimball2, Ana Lucia Yanez-Felix4
1Departamento de Medicina Genómica y Toxicología Ambiental, Universidad Nacional Autónoma de México, México City, Mexico.
Insights
Inherited bone marrow failure syndromes (IBMFSs) were suspected in 48 Mexican pediatric patients. Clinical data identified specific IBMFSs in 70%, but 27% remained undefined, highlighting the need for advanced diagnostics.
Area of Science:
- Pediatric Hematology
- Clinical Genetics
- Rare Diseases
Background:
- Inherited bone marrow failure syndromes (IBMFSs) are rare genetic disorders.
- IBMFSs present with bone marrow failure, physical abnormalities, and increased cancer risk.
- Diagnosis is challenging, especially where advanced genetic sequencing is unavailable.
Purpose of the Study:
- To describe a cohort of Mexican pediatric patients with suspected IBMFS.
- To analyze clinical and hematological features aiding IBMFS diagnosis.
- To identify specific IBMFS subtypes and the prevalence of undefined cases.
Main Methods:
- Retrospective analysis of medical records (Jan 2018 - July 2021) at the National Institute of Pediatrics (INP).
- Exclusion of acquired causes of bone marrow failure.
- Clinical dysmorphology assessment for specific IBMFS phenotypes.
- Classification into specific IBMFS (DC, DBA, SDS, TAR, SCN) and undefined IBMFS (UI).
Main Results:
- High IBMFS suspicion in 48 patients; most common hematologic findings were bicytopenia (20%) and aplastic anemia (16%).
- Frequent physical abnormalities included minor craniofacial features (83%) and neurodevelopmental disorders (52%).
- Specific IBMFS suspicions: Diamond-Blackfan anemia (31%), Shwachman-Diamond syndrome (18%), Dyskeratosis congenita (14%), while 27% remained undefined.
Conclusions:
- Clinical evaluation enabled suspicion of specific IBMFS in ~70% of cases.
- A significant portion of patients remained with undefined IBMFS, indicating diagnostic gaps.
- Next-generation sequencing and telomere length measurement are crucial for improving IBMFS diagnosis in Mexico.
Abstract:
Introduction: The inherited bone marrow failure syndromes (IBMFSs) are a group of rare disorders characterized by bone marrow failure (BMF), physical abnormalities, and an increased risk of neoplasia. The National Institute of Pediatrics (INP) is a major medical institution in Mexico, where patients with BMF receive a complete approach that includes paraclinical tests. Readily recognizable features, such as the hematological and distinctive physical phenotypes, identified by clinical dysmorphologists, remain crucial for the diagnosis and management of these patients, particularly in circumstances where next-generation sequencing (NGS) is not easily available. Here, we describe a group of Mexican patients with a high clinical suspicion of an IBMFS. Methods: We performed a systematic retrospective analysis of the medical records of patients who had a high IBMFS suspicion at our institution from January 2018 to July 2021. An initial assessment included first ruling out acquired causes of BMF by the Hematology Department and referral of the patient to the Department of Human Genetics for physical examination to search for specific phenotypes suggesting an IBMFS. Patients with high suspicion of having an IBMFS were classified into two main groups: 1) specific IBMFS, including dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS), thrombocytopenia with absent radii (TAR), and severe congenital neutropenia (SCN); 2) undefined IBMFS (UI). Results: We established a high suspicion of having an IBMFS in 48 patients. At initial evaluation, the most common hematologic features were bicytopenia (20%) and aplastic anemia (16%); three patients received hematopoietic stem cell transplantation. Among patients with a suspicion of an IBMFS, the most common physical abnormality was minor craniofacial features in 83% of patients and neurodevelopmental disorders in 52%. The specific suspicions that we built were DBA (31%), SDS (18%), DC (14%), TAR (4%), and SCN (4%), whereas 27% of cases remained as undefined IBMFS. SDS, TAR, and SCN were more commonly suspected at an earlier age (<1 year), followed by DBA (2 years) and DC (5 years). Conclusions: Thorough examination of reported clinical data allowed us to highly suspect a specific IBMFS in approximately 70% of patients; however, an important number of patients remained with suspicion of an undefined IBMFS. Implementation of NGS and telomere length measurement are forthcoming measures to improve IBMFS diagnosis in Mexico.
