Clinical trial NCT05436587: Mutations and Phenotypes of Unclassifiable Inherited Bone Marrow Failure Syndromes
Official title: Identification of The Novel Mutations and A Comprehensive Analysis of The Phenotype and Genetic Etiology Underlying Unclassifiable Inherited Bone Marrow Failure Syndromes With Bone Fragility Fractures
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inherited BMF Syndrome
Lead sponsor: Sohag University
Sponsor class: OTHER
Collaborators: name: Kyoto University
name: Assiut University
First posted: 2022-06-29
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The candidate patients who will have evidence of unclassifiable IBMFSs and/or will present with manifestations suggesting IBMFSs and agree to comply with follow-up instructions will be screened for enrollment in this study.

Brief summary: Inherited bone marrow failure syndromes (IBMFSs) are a diverse collection of genetic illnesses characterized by various degrees of peripheral cytopenias due to defective single-lineage or multi-lineage hematopoiesis, it can manifest itself at birth or later in life.

Detailed description: Studying the genetic etiology underlying unclassifiable IBMFSs with bone fragility fractures should be useful for clarifying the undiagnosed pathophysiological mechanisms and other accessory factors to improve the diagnosis, follow-up, prognosis, and management of these patients as well as prevent future complications.

Moreover, early diagnosis of risk factors of unusual presentations of IBMFSs will be a useful tool for better treatment strategy.

In addition, along with typical IBMFSs, novel clinical entities must be included in an overall molecular portrait of IBMF disorders. As a result, comprehensive genetic analysis will be effective in establishing an accurate genetic diagnosis at medical evaluation.

Eligibility criteria: Inclusion Criteria:

* Confirmed a two-generational family with IBMFSs presented with signs and symptoms of bone fragility fractures and admitted or treated in Hematology Division at Internal Medicine Departments of various university hospitals will be screened for enrollment in this study.
* The investigators will invite the entire family for testing for IBMFSs mutations, and three additional family members consented to participate in this study.

Exclusion Criteria:

* • Patients will be diagnosed with paroxysmal nocturnal hemoglobinuria

  * Patients will be diagnosed with de novo myelodysplastic syndrome
  * IBMFSs-patients will refuse to consent to this study.
  * Serologic evidence of recent virus infection as hepatitis A (HAV), HBV, HCV, HEV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), or positive test for HIV.
  * IBMFSs patients with severe systemic diseases (such as cardiovascular, renal, and hepatic disease) or surgical/medical conditions that might interfere with follow-up instructions.
  * IBMFs patients with psychiatric disorders or a history of drug abuse,

Primary outcomes:
measure: Number of Participants with Progression of pancytopenia
timeFrame: Two year after diagnosis
measure: Number of Participants with Fragility Fractures
timeFrame: Two year after diagnosis
measure: Number of Participants with Malignancy transformation
timeFrame: Two year after diagnosis
Secondary outcomes:
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: , Faculty of Medicine, Sohag University
Study officials:
affiliation: Faculty of Medicine, Sohag University
name: Mahmoud I Yousef, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sieff CA. Acquired and Inherited Bone Marrow Failure Syndromes. Hematol Oncol Clin North Am. 2018 Aug;32(4):xiii-xiv. doi: 10.1016/j.hoc.2018.05.001. No abstract available.