Autosomal recessive inherited disorder characterized by prenatal and postnatal growth retardation, photosensitivity, telangiectasias, skin pigment anomalies, and increased risk of malignancies most likely due to chromosomal instability.
Congenital Telangiectatic Erythema; Bloom-Machacek-Torre Syndrome.
First published by the American dermatologist David Bloom in 1954, who reported about three patients. The synonymous name Bloom-Machacek-Torre Syndrome is explained by the fact that G. F. Machacek and D. P. Torre were the two colleagues of Bloom who presented one each of the initial three patients described by Bloom.
1:160,000 live births. Less than 300 patients are registered with the Bloom’s Syndrome Registry hosted at Weill Cornell Medical College (http://weill.cornell.edu/bsr/). About one-third of all patients are Ashkenazi Jews from Central and Eastern Europe.
Autosomal recessive. The disease is caused by homozygous or compound heterozygous mutations in the BLM (Bloom Syndrome) gene on chromosome 15q26, which encodes the DNA-helicase RecQ-protein-like 3 (RECQL3). This enzyme is involved in DNA-replication and DNA-repair, which not only protects from ultraviolet light-induced damage, but most likely also plays a role in suppressing cancerogenesis. Heterozygotes (carriers) are asymptomatic.
The normal RECQL3 protein (DNA helicase) is involved in the maintenance of genomic stability. A mutation in this gene results in Bloom Syndrome. Spontaneous chromosome breakage with exchanges between homologous chromosome segments leads to increased sister chromatid exchanges, which are thought to be responsible for the phenotype and the predisposition to neoplasias.
Based on the clinical findings, but confirmation requires molecular genetic testing. Amniocentesis for amniotic fluid cell cultures with assessment of the number of sister chromatid exchanges allows prenatal diagnosis.
Most patients are of normal intelligence, but a minority has been diagnosed with some degree of learning difficulties. Significant prenatal and postnatal growth retardation resulting in proportionate short stature throughout life are the hallmarks of this syndrome and usually the first reason to seek medical attention. Growth hormone levels are typically normal and the response to growth hormone therapy is limited. Other clinical signs include dolichocephaly, malar and mandibular hypoplasia and occasional mild microcephaly resulting in disproportionately large appearing nose, reduced subcutaneous fat tissue, increased generalized photosensitivity with telangiectasias and erythema in sun-exposed areas (ie, typically in the face with butterfly-like midface distribution), but also other exposed locations (presenting as plaques or macules), café-au-lait spots, and chronic bullous skin eruptions on the lower lip (sun exposure). Decreased subcutaneous fat makes these patients look older than they are. A high-pitched voice has already been described by Bloom, but no anatomical correlate has been mentioned. Pulmonary fibrosis and bronchiectases are variable findings. Gastroesophageal reflux is common and may ...