Congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome

What it is

From: Orphanet

A rare multiple congenital anomalies/dysmorphic syndrome characterized by early-onset progressive bone marrow failure with anemia, leukopenia, mild thrombopenia, and myelodysplastic features, as well as non-hematologic manifestations, such as developmental delay, cataracts, facial dysmorphism, short stature, and skeletal anomalies. Immunodeficiency primarily affects B-cells and may lead to increased susceptibility to infections. Additional reported features include dry skin and eczema, cardiac anomalies, hearing loss, and reduction of cerebral volume on brain imaging.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Anemia · Very frequent (99-80%)

A reduction in erythrocytes volume or hemoglobin concentration.

Bone marrow hypocellularity · Very frequent (99-80%)

A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.

Abnormal facial shape · Frequent (79-30%)

An abnormal morphology (form) of the face or its components.

Cerebral hypoplasia · Frequent (79-30%)

Underdevelopment of the cerebrum.

Coarse facial features · Frequent (79-30%)

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Congestive heart failure · Frequent (79-30%)

The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.

Decreased total B cell count · Frequent (79-30%)

The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group.

Decreased total neutrophil count · Frequent (79-30%)

Abnormal decrease of absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group.

Erythroid dysplasia · Frequent (79-30%)

Dysplasia in the erythroid lineage, which presents with a variety of morphological changes in the bone marrow, including nuclear budding or irregular nuclear contour in erythroblasts.

Intellectual disability · Frequent (79-30%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Leukopenia · Frequent (79-30%)

An abnormal decreased number of leukocytes in the blood.

Lymphopenia · Frequent (79-30%)

A reduced number of lymphocytes in the blood.

Megakaryocyte dysplasia · Frequent (79-30%)

The presence of micro-megakaryocytes, hypo-lobed, or non-lobed nuclei in megakaryocytes of all sizes and multiple, widely-separated nuclei.

Myelodysplasia · Frequent (79-30%)

Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.

Other findings in the same source

From: Orphanet

Additional reported features include Neurodevelopmental delay (Frequent (79-30%)); Recurrent upper respiratory tract infections (Frequent (79-30%)); Reticulocytopenia (Frequent (79-30%)); Short stature (Frequent (79-30%)); Thrombocytopenia (Frequent (79-30%)); Abnormal thorax morphology (Occasional (29-5%)); Brachydactyly (Occasional (29-5%)); Broad clavicles (Occasional (29-5%)); Cataract (Occasional (29-5%)); Delayed eruption of teeth (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 5.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.