DGM (Dutch-German Mennonites)

Inheritance: autosomal recessive
Genes: DNA helicase RecQ protein-like-3

BLM
BS
BLS

Growth deficiency
Telangiectases
Skin pigmentation
Malignancy
Chromosomal instability
Diabetes

Bloom Syndrome

Clinical Characteristics

General description (for patients):  

Bloom syndrome causes growth deficiency both before and after birth.  Low birth weight and failure to thrive are common.  It is associated with abnormal and sun-sensitive skin pigmentation and ‘spidery’ blood vessels.  Chromosomes are fragile in this condition with frequent fragmentation and an associated increased risk of malignancies (see also ataxia-telangiectasia).  Children are at considerable risk of leukemia.

Medical description:  

Bloom syndrome confers an increased risk of malignancy possibly as a consequence of non-specific chromosomal fragility.  Pre- and postnatal growth deficiency, diabetes mellitus, and sun-sensitive hypo- and hyperpigmented skin with telangiectases are also features.  Leukopenic leukemia is an especially serious risk in children and is difficult to treat.

Genetics:   

This is an autosomal recessive disorder resulting from mutations in the gene encoding DNA helicase RecQ protein-like-3 leading to structural alterations.  It is found predominantly in Ashkenazi Jews.  However an identical ligase I structural defect was found in a single Canadian Mennonite sibship with two children, a 3 year old and a 14 month old, born to a consanguineous couple.  The youngest had a Wilm’s tumor.

Treatment:  

No effective treatment has been found.

Prognosis:  

Survival into adult years is the exception as the result of malignancies.

Ancillary treatments and support:

Avoidance of sun exposure, treatment of malignancies.

Specialists and specialty centers:  

Pediatrician, Hematologist, Oncologist.

References:

Weksberg, R., Smith, C., Anson-Cartwright, L., and Maloney, K.:  Bloom syndrome: a single complementation group defines patients of diverse ethnic origin.  Am. J. Hum. Genet. 42: 816-824, 1988. PubMed ID: 3163468

Willis, A.E., Weksberg, R., Tomlinson, S., and Lindahl, T.:  Structural alterations of DNA ligase I in Bloom syndrome.  Proc. Nat. Acad. Sci. 84: 8016-8020, 1987.  PubMed ID: 3479778

Ellis, N.A., and German, J.:  Molecular genetics of Bloom’s syndrome.  Hum. Molec. Genet. 5: 1457-1463. PubMed ID: 8875252

Resources:

Bloom's Syndrome Foundation