Pelger-Huet anomaly is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. (Hoffmann et al., 2002). Heterozygotes show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as ... Pelger-Huet anomaly is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. (Hoffmann et al., 2002). Heterozygotes show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy, and skeletal abnormalities. The nucleus of the granulocytes is hyposegmented, being rodlike, dumbbell- or peanut-shaped, or spectaclelike. This anomaly is also found in the rabbit. The homozygote in the rabbit has chondrodystrophy (Nachtsheim, 1950). Stobbe and Jorke (1965) posited that skeletal abnormality apparently does not occur in the human homozygote. However, Aznar and Vaya (1981) described a presumed homozygote in whom postaxial polydactyly of all 4 limbs was also present. See also Haverkamp Begemann and van Lookeren Campagne (1952). Hoffmann et al. (2002) identified a man homozygous for Pelger-Huet anomaly who had 2 parents who were heterozygotes and himself showed not the typical bilobed nucleus but a round nucleus in neutrophils; he also showed short metacarpals in some fingers. Rioux et al. (1968) reported an extensively affected French-Canadian kindred. The nuclei of leukocytes had a pince-nez appearance. Oneson et al. (1987) described a child with familial Pelger-Huet anomaly who developed acute lymphoblastic leukemia. The disorder is effectively detected by the average lobe index (ALI) of the neutrophils. The ALI is the total number of nuclear lobes in 100 neutrophils divided by 100. The normal range for ALI is 2.5 to 3.1 (mean, 2.8). ALI in the affected nonleukemic members of this family varied from 1.12 to 1.60, with the lowest values in children and the highest values in adults. That folate deficiency increases segmentation was indicated by the fact that the ALI of the proband increased during 6-mercaptopurine and methotrexate therapy. Elevation of temperature to 42 degrees C resulted in an increase in the ALI of both normal cells and cells with the Pelger-Huet anomaly. Fishbein and Falletta (1991) described a newborn with Pelger-Huet anomaly associated with multiple congenital anomalies (diaphragmatic hernia, coarse facies, and distal limb anomalies) suggestive of Fryns syndrome. The parents did not have the blood anomaly.
To identify the genetic cause of PHA, Hoffmann et al. (2002) studied 11 families from Gelenau with 18 unaffected and 29 affected members, including a presumed homozygous individual. In contrast to the neutrophils of healthy subjects, all neutrophils ... To identify the genetic cause of PHA, Hoffmann et al. (2002) studied 11 families from Gelenau with 18 unaffected and 29 affected members, including a presumed homozygous individual. In contrast to the neutrophils of healthy subjects, all neutrophils of individuals of PHA had bilobed or rod-like nuclei. The presumed homozygous individuals had neutrophils with round, nonsegmented nuclei and presented with mental retardation, disproportionate body habitus, macrocephalus with prominent forehead, ventricular septal defect, and short metacarpals in several fingers. Hoffmann et al. (2002) identified a founder haplotype in 10 of the 11 families. The affected members of these 10 families carried the same mutation, a 5-bp deletion in the 3-prime splice site region of intron 12 of the LBR gene (600024.0001). In the affected individual in the eleventh family, a different splice acceptor site mutation was found, in intron 2 of LBR (600024.0002). Six further mutations in LBR were found in individuals from Spain, the United States, and Mexico. Only splice site, frameshift, and nonsense mutations were found. The lethal autosomal recessive fetal chondrodystrophy hydrops-ectopic calcification-'moth-eaten' (HEM), or Greenberg, skeletal dysplasia (215140) is caused by lack of the 3-beta-hydroxysterol delta(14)-reductase activity of the LBR gene resulting from homozygous mutations in the gene. Waterham et al. (2003) suggested that Pelger-Huet anomaly represents the heterozygous state of this deficiency. Oosterwijk et al. (2003), however, identified 11 reported patients with Pelger-Huet anomaly and homozygosity for mutations in the LBR gene and found that none had skeletal dysplasia, early lethality, congenital abnormalities, or skin abnormalities. They suggested that homozygous LBR mutations result in distinct mild (PHA homozygosity) or severe (Greenberg skeletal dysplasia) phenotypes based on allelic heterogeneity.
In Spokane, Washington, Ludden and Harvey (1962) found 4 cases among 43,000 persons. Affected persons were of German or Dutch descent. In Cleveland, Skendzel and Hoffman (1962) found a frequency of 1 in 4,785 routine smears. All figures ... In Spokane, Washington, Ludden and Harvey (1962) found 4 cases among 43,000 persons. Affected persons were of German or Dutch descent. In Cleveland, Skendzel and Hoffman (1962) found a frequency of 1 in 4,785 routine smears. All figures in this country and also that of Davidson in England (1 in 6,000) are lower than that of Nachtsheim (1 in 1,020). The frequency of PHA is estimated to be approximately 0.01-0.1% (Skendzel and Hoffman, 1962), but the frequency is much higher in Vasterbotten County in northern Sweden (0.6%) and in the mountain village of Gelenau in southeastern Germany (1.01%), according to Hoffmann et al. (2002), who did positional cloning studies in families from the latter region.