| Pelger–Huët anomaly |
| Classification and external resources |
| Specialty |
hematology |
| ICD-10 |
D72.0 |
| ICD-9-CM |
288.2 |
| OMIM |
169400 |
| DiseasesDB |
29515 |
| eMedicine |
ped/1753 |
| MeSH |
D010381 |
|
[edit on Wikidata]
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Pelger–Huët anomaly (pronunciation: [pel′gər hyo̅o̅′ət]) is a blood laminopathy associated with the lamin B receptor.[1]
It is characterized by a white blood cell type known as a neutrophil whose nucleus is hyposegmented.[citation needed]
Pelger–Huët anomaly has an autosomal dominant pattern of inheritance.
It is a genetic disorder with an autosomal dominant inheritance pattern. Heterozygotes are clinically normal, although their neutrophils may be mistaken for immature cells which may cause mistreatment in a clinical setting. Homozygotes tend to have neutrophils with rounded nuclei that do have some functional problems.[citation needed]
Congenital Pelger–Huët anomaly
Is a benign dominantly inherited defect of terminal neutrophil differentiation as a result of mutations in the lamin B receptor gene. The characteristic leukocyte appearance was first reported in 1928 by Pelger, a Dutch hematologist, who described leukocytes with dumbbell-shaped bilobed nuclei, a reduced number of nuclear segments, and coarse clumping of the nuclear chromatin. In 1931 Huet, a pediatrician, identified it as an inherited disorder.[2]
It is a genetic disorder with an autosomal dominant inheritance pattern.[1][3] Heterozygotes are clinically normal, although their neutrophils may be mistaken for immature cells, which may cause mistreatment in a clinical setting. Homozygotes tend to have neutrophils with rounded nuclei that do have some functional problems. Homozygous individuals inconsistently have skeletal anomalies such as post-axial polydactyly, short metacarpals, short upper limbs, short stature, or hyperkyphosis.[citation needed]
Identifying Pelger–Huët anomaly is important to differentiate from bandemia with a left-shifted peripheral blood smear and neutrophilic band forms and from an increase in young neutrophilic forms that can be observed in association with infection.[citation needed]
Acquired or pseudo-Pelger–Huët anomaly
Anomalies resembling Pelger–Huët anomaly that are acquired rather than congenital have been described as pseudo Pelger–Huët anomaly. These can develop in the course of acute myelogenous leukemia or chronic myelogenous leukemia and in myelodysplastic syndrome. It has also been described in Filovirus disease.[4]
In patients with these conditions, the pseudo–Pelger–Huët cells tend to appear late in the disease and often appear after considerable chemotherapy has been administered. The morphologic changes have also been described in myxedema associated with panhypopituitarism, vitamin B12 and folate deficiency, multiple myeloma, enteroviral infections, malaria, muscular dystrophy, leukemoid reaction secondary to metastases to the bone marrow, and drug sensitivity, sulfa and valproate toxicities[5] are examples. In some of these conditions, especially the drug-induced cases, identifying the change as Pelger–Huët anomaly is important because it obviates the need for further unnecessary testing for cancer.[citation needed]
Peripheral blood smear shows a predominance of neutrophils with bilobed nuclei which are composed of two nuclear masses connected with a thin filament of chromatin. It resembles the pince-nez glasses, so it is often referred to as pince-nez appearance. Usually the congenital form is not associated with thrombocytopenia and leukopenia, so if these features are present more detailed search for myelodysplasia is warranted, as pseudo-Pelger–Huët anomaly can be an early feature of myelodysplasia.[6]
References
- ^ a b Hoffmann, Katrin; Dreger, Christine K.; Olins, Ada L.; Olins, Donald E.; Shultz, Leonard D.; Lucke, Barbara; Karl, Hartmut; Kaps, Reinhard; Müller, Dietmar; Vayá, Amparo; Aznar, Justo; Ware, Russell E.; Cruz, Norberto Sotelo; Lindner, Tom H.; Herrmann, Harald; Reis, André; Sperling, Karl (2002). "Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger–Huët anomaly)". Nature Genetics 31 (4): 410–4. doi:10.1038/ng925. PMID 12118250.
- ^ Cunningham, John M.; Patnaik, Mrinal M.; Hammerschmidt, Dale E.; Vercellotti, Gregory M. (2009). "Historical perspective and clinical implications of the Pelger-Huet cell". American Journal of Hematology 84 (2): 116–9. doi:10.1002/ajh.21320. PMID 19021122.
- ^ Vale, A. M.; Tomaz, L. R.; Sousa, R. S.; Soto-Blanco, B. (2011). "Pelger-Huët anomaly in two related mixed-breed dogs". Journal of Veterinary Diagnostic Investigation 23 (4): 863–5. doi:10.1177/1040638711407891. PMID 21908340.
- ^ Gear, JS; Cassel, GA; Gear, AJ; Trappler, B; Clausen, L; Meyers, AM; Kew, MC; Bothwell, TH; Sher, R; Miller, GB; Schneider, J; Koornhof, HJ; Gomperts, ED; Isaäcson, M; Gear, JH (1975). "Outbreake of Marburg virus disease in Johannesburg". British Medical Journal 4 (5995): 489–93. doi:10.1136/bmj.4.5995.489. PMC 1675587. PMID 811315.
- ^ Singh, Nishith K.; Nagendra, Sanjai (2008). "Reversible Neutrophil Abnormalities Related to Supratherapeutic Valproic Acid Levels". Mayo Clinic Proceedings 83 (5): 600. doi:10.4065/83.5.600. PMID 18452694.
- ^ Pelger-Huet Anomaly at eMedicine
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Cytoskeletal defects
|
|
| Microfilaments |
| Myofilament |
| Actin |
- Hypertrophic cardiomyopathy 11
- Dilated cardiomyopathy 1AA
- DFNA20
- Nemaline myopathy 3
|
|
| Myosin |
- Elejalde syndrome
- Hypertrophic cardiomyopathy 1, 8, 10
- Usher syndrome 1B
- Freeman–Sheldon syndrome
- DFN A3, 4, 11, 17, 22; B2, 30, 37, 48
- May-Hegglin anomaly
|
|
| Troponin |
- Hypertrophic cardiomyopathy 7, 2
- Nemaline myopathy 4, 5
|
|
| Tropomyosin |
- Hypertrophic cardiomyopathy 3
- Nemaline myopathy 1
|
|
| Titin |
- Hypertrophic cardiomyopathy 9
|
|
|
| Other |
- Fibrillin
- Marfan syndrome
- Weill-Marchesani syndrome
- Filamin
- FG syndrome 2
- Boomerang dysplasia
- Larsen syndrome
- Terminal osseous dysplasia with pigmentary defects
|
|
|
| IF |
| 1/2 |
- Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1
- Striate palmoplantar keratoderma 3
- Epidermolytic hyperkeratosis
- IHCM
- KRT2E (Ichthyosis bullosa of Siemens)
- KRT3 (Meesmann juvenile epithelial corneal dystrophy)
- KRT4 (White sponge nevus)
- KRT5 (Epidermolysis bullosa simplex)
- KRT8 (Familial cirrhosis)
- KRT10 (Epidermolytic hyperkeratosis)
- KRT12 (Meesmann juvenile epithelial corneal dystrophy)
- KRT13 (White sponge nevus)
- KRT14 (Epidermolysis bullosa simplex)
- KRT17 (Steatocystoma multiplex)
- KRT18 (Familial cirrhosis)
- KRT81/KRT83/KRT86 (Monilethrix)
- Naegeli–Franceschetti–Jadassohn syndrome
- Reticular pigmented anomaly of the flexures
|
|
| 3 |
- Desmin: Desmin-related myofibrillar myopathy
- Dilated cardiomyopathy 1I
- Peripherin: Amyotrophic lateral sclerosis
|
|
| 4 |
- Neurofilament: Parkinson's disease
- Charcot–Marie–Tooth disease 1F, 2E
- Amyotrophic lateral sclerosis
|
|
| 5 |
- Laminopathy: LMNA
- Mandibuloacral dysplasia
- Dunnigan Familial partial lipodystrophy
- Emery-Dreifuss muscular dystrophy 2
- Limb-girdle muscular dystrophy 1B
- Charcot–Marie–Tooth disease 2B1
- LMNB
- Barraquer–Simons syndrome
- LEMD3
- Buschke–Ollendorff syndrome
- Osteopoikilosis
- LBR
- Pelger-Huet anomaly
- Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
|
|
|
| Microtubules |
| Kinesin |
- Charcot–Marie–Tooth disease 2A
- Hereditary spastic paraplegia 10
|
|
| Dynein |
- Primary ciliary dyskinesia
- Short rib-polydactyly syndrome 3
- Asphyxiating thoracic dysplasia 3
|
|
| Other |
- Tauopathy
- Cavernous venous malformation
|
|
|
| Membrane |
- Spectrin: Spinocerebellar ataxia 5
- Hereditary spherocytosis 2, 3
- Hereditary elliptocytosis 2, 3
Ankyrin: Long QT syndrome 4
- Hereditary spherocytosis 1
|
|
| Catenin |
- APC
- Gardner's syndrome
- Familial adenomatous polyposis
- plakoglobin (Naxos syndrome)
- GAN (Giant axonal neuropathy)
|
|
| Other |
- desmoplakin: Striate palmoplantar keratoderma 2
- Carvajal syndrome
- Arrhythmogenic right ventricular dysplasia 8
- plectin: Epidermolysis bullosa simplex with muscular dystrophy
- Epidermolysis bullosa simplex of Ogna
- plakophilin: Skin fragility syndrome
- Arrhythmogenic right ventricular dysplasia 9
- centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II)
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See also: cytoskeletal proteins
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