Bloom Syndrome (BSyn) is a very rare genetic disorder that belongs to the group of chromosome breakage syndromes [1] and leads to a marked genomic instability. The main clinical characteristics are an increased sensitivity to sunlight that often causes a typical butterfly-shaped facial erythema, pre- and postnatal growth deficiency leading to proportionate microsomia and predisposition to malignancies at an unusual early age limiting life expectancy. Anesthesiologic care may be complicated by associated characteristic facial dysmorphic features that may contribute to significant difficulties during airway access as well as chronic pulmonary disease, endocrinological pathologies and a mild immunodeficiency. Pediatric patients are also particularly prone to gastroesophageal reflux, vomiting and severe dehydration during infancy [2].
BSyn is caused by an autosomal recessive inheritance of loss-of-function mutations in the BLM gene, which encodes for a RecQ helicase involved in DNA replication and repair. Its exact prevalence is unknown but due to a founder mutation it is most common in people with Ashkenazi Jewish descent, where it is estimated to affect 1:48.000 people and the carrier frequency is about 1:100. However, BSyn has been found in individuals of many ethnic groups and up to now only 25% of affected patients can be explained by founder effects [2,3]. In the West European population, the incidence is estimated to be at least about 1:500.000 live births but could be underestimated due to lack of information [1].
Nonetheless, because of its rarity there is only limited literature available and much of the knowledge has been obtained from data of approximately 300 patients enrolled in the BSyn registry as well as by a few case reports [3].
A phenotype of proportionate microsomia in combination with some of the following characteristic features should alert clinicians and patients need to be referred to a genetic specialist for further diagnosis [3].
The facial appearance often comprises a combination of dysmorphic features like microcephaly, flat malar region and small mandible with hypo- and/or retrognathia as well as prominence of the ears and nose [4].
During early childhood increased UV sensitivity leads to a typical butterfly-shaped facial erythema of nose and cheeks after exposure to sunlight. As severity of erythematous lesions is highly variable and the common facial lesions can be completely absent, diagnosis can be delayed [4,5].
The most striking clinical burden in patients with BSyn is their predisposition to various types of cancer at an unusual early age. During the first two decades leukemias and lymphomas are observed most frequently, followed by solid cancers especially of colon, breast, skin and neck in early adulthood [2]. According to recent data from the BSyn registry, 53% of all patients suffer from at least one type of cancer and chemotherapeutic approaches are challenging because of the patients’ increased sensitivity. Although life expectancy has increased during the last decades due to improvements in surveillance programs and cancer treatment, the median age at death is 30.5 years [1,6].
Additional symptoms are associated with BSyn and need further attention:
A major and sometimes life-limiting complication is an early onset of chronic obstructive lung disease that can progress to respiratory failure [7].
Several endocrinological pathologies have been assigned to BSyn. These most commonly include an early onset of insulin resistance and type 2 diabetes as well as hypothyroidism and dyslipidemia, which are usually treated following standard protocols [8]. Microsomia is caused by pre- and postnatal growth deficiency and besides being of small stature many patients are underweight for their size and subcutaneous adipose tissue is reduced [9]. Malnutrition is especially a problem in infancy and may often improve during childhood. Due to feeding problems and a high frequency of gastroesophageal reflux as well as pronounced episodes of vomiting and diarrhea, infants are prone to severe dehydration [2].
There are several immune abnormalities described, which are highly variable but usually not severe. Therefore, most patients show an increased susceptibility for common infections especially of the upper respiratory tract and middle ear, but some have low levels of one or more classes of plasma immunoglobulins that can rarely also impair vaccine response [10,11].
Cognitive ability varies from normal to limited [2] but is usually within the normal range [7]. However, some patients experience learning difficulties, attention related issues or psychological consequences of their unusual appearance and clinical complications [4].
Impaired fertility is common in BSyn. Unlike affected males who are mostly infertile [10], female patients are subfertile but often experience premature ovarian failure. There are few reports of pregnancies in women with BSyn [3] giving birth to healthy offspring who are obligate carriers of the BLM mutation. However, more detailed references coincidently describe preterm delivery of babies small for gestational age [12,13].
Heterozygous carriers of BLM mutations are asymptomatic. Although pathophysiology suggests an increased tumor risk for unaffected carries in chromosome instability syndromes, this has not been consistently confirmed for BLM mutations and contradictory data needs further investigation [1,14].
As there is no causative therapeutic option, treatment of BSyn mainly relies on restriction of exposure to DNA-damaging agents including sunlight, ionizing radiation and alkylating substances as well as early screening for neoplasia and endocrinological problems. Recurrent infections need appropriate treatment to avoid complications and sometimes immunoglobulin substitution is required. Concerning growth deficiency and feeding problems during (early) childhood, tube feeding and growth hormone treatment have not proven to be beneficial and are generally not recommended, the latter because of the possibility of increasing the risks for malignancies [9].