Pelger–Huët anomaly

Genetic blood disorder with abnormal neutrophil nuclei

Pelger–Huët anomaly
Synonyms	PHA, Pelger anomaly, Huët anomaly
Pronounce	nl
Field	N/A
Symptoms	N/A
Complications	Generally benign in heterozygotes; potential immune dysfunction in homozygotes
Onset	Congenital
Duration	Lifelong
Types	Congenital Pelger–Huët anomaly, Pseudo–Pelger–Huët anomaly
Causes	Mutation in the lamin B receptor (LBR) gene
Risks	Family history of the disorder
Diagnosis	Peripheral blood smear, genetic testing
Differential diagnosis	Pseudo–Pelger–Huët anomaly, Myelodysplastic syndrome
Prevention	None
Treatment	Supportive; no specific treatment needed for congenital form
Medication	None
Prognosis	Excellent for heterozygous congenital form
Frequency	Rare
Deaths	None (for congenital form)

Pelger–Huët anomaly has an autosomal dominant pattern of inheritance.

Pelger–Huët anomaly (PHA) is a rare, benign genetic disorder affecting the white blood cells, primarily the neutrophils and eosinophils. It is classified as a type of laminopathy and results from mutations in the lamin B receptor (LBR) gene. The hallmark of PHA is the abnormal shape of the cell nucleus, which typically appears as bilobed, peanut-shaped, or dumbbell-shaped, rather than the usual multi-lobed (trilobed) configuration.

History

The condition was first described in 1928 by Dutch hematologist Karel Pelger, who noted the distinctive appearance of neutrophil nuclei. In 1931, Gauthier Jean Huët, a Dutch pediatrician, recognized the hereditary nature of this anomaly, leading to the eponymous naming of the disorder.

Pathophysiology

The lamin B receptor gene, located on chromosome 1q42.1, encodes an inner nuclear membrane protein involved in chromatin organization and nuclear envelope stability. Mutations in this gene disrupt the terminal differentiation of neutrophils, leading to characteristic nuclear hyposegmentation.

Genetics

Pelger–Huët anomaly is inherited in an autosomal dominant pattern:

• Heterozygotes exhibit typical bilobed or hyposegmented nuclei in neutrophils but are clinically asymptomatic.
• Homozygotes may present with more pronounced nuclear abnormalities and can have mild hematological dysfunction, including altered neutrophil mobility and impaired chemotaxis.

Types

Congenital Pelger–Huët anomaly

The congenital form is inherited and considered benign. It is not associated with illness or increased susceptibility to infection in heterozygous carriers. The neutrophils in these individuals retain normal function despite abnormal nuclear morphology.

Pseudo–Pelger–Huët anomaly

This is an acquired form and may occur in association with:

• Myelodysplastic syndrome (MDS)
• Acute myeloid leukemia (AML)
• Chronic myelogenous leukemia (CML)
• HIV/AIDS
• After exposure to certain medications (e.g., chemotherapeutic agents, immunosuppressants)

This form can be an indicator of serious underlying pathology and requires further investigation.

Diagnosis

Diagnosis of Pelger–Huët anomaly includes:

• **Peripheral blood smear**: Neutrophils with bilobed or round nuclei and dense clumped chromatin.
• **Genetic testing**: Confirmation of LBR gene mutation if necessary.
• **Family history**: Important to distinguish congenital from acquired forms.

Differential diagnosis

• Pseudo–Pelger–Huët anomaly due to underlying hematologic disease
• Neutrophil dysplasia in myelodysplastic syndromes
• Left shift in infection or stress

Clinical significance

While Pelger–Huët anomaly is largely benign in congenital form, it is crucial to distinguish it from its pseudo-form to avoid misdiagnosis. Misinterpretation as immature granulocytes can lead to inappropriate clinical management.

Management

No treatment is required for the congenital form. Recognition of the anomaly prevents unnecessary diagnostic testing or treatment.

For the acquired (pseudo) form, management involves addressing the underlying disease or discontinuing the causative medication.

See also

• Laminopathy
• Neutrophil
• White blood cell
• Hematology
• Myelodysplastic syndrome

External links

• OMIM Entry: Pelger–Huët anomaly
• NCBI: Pelger–Huët Anomaly Overview