Familial monosomy 7 syndrome

2001-07-01   Jay L. Hess  

Department of Pathology, The University of Michigan, M5240 Medical Science I, 1301 Catherine Avenue, Ann Arbor, MI 48109-0602, USA

Identity

Name

Familial monosomy 7 syndrome

Alias

Familial leukemia or MDS associated with monosomy 7

Note

Monosomy 7 is seen in a variety of hematologic disorders:
 , 
  • 1- de novo myelodysplastic disorders (MDS) and ANLL , 
  • 2- Therapy-related MDS and ANLL , 
  • 3- Childhood myeloproliferative \/myelodysplastic disorder commonly referred to as the childhood monosomy 7 syndrome, which is associated with a subset of juvenile myelomonocytic leukemia (JMML, JCML). , 
  • 4- MDS or ANLL associated with constitutional predispositions to myeloid leukemia including Fanconi anemia, congenital neutropenia, and neurofibromatosis type 1. , 
  • 5- Familial monosomy 7 syndrome- Rare familial cases of MDS or ANLL associated with either complete or partial monosomy 7 have been reported in 12 pedigrees.

    • Inheritance

    In some pedigrees the pattern of involvement is compatible with an autosomal dominant inheritance pattern with incomplete penetrance.

    Omim

    252270

    Mesh

    D012804

    Orphanet

    166282 Familial sick sinus syndrome

    Umls

    C0037052

    Clinics

    Phenotype and clinics

  • Disease: Hematologic disorder characterized by either marrow aplasia, dysplasia, or frank acute myeloid leukemia occurring in at least two siblings associated with either partial or complete loss of chromosome 7. The majority of reported cases of familial monosomy 7 present at an early age (20 out of 24 cases before age 20 years) with either MDS or ANLL.
  • Phenotype\/cell of origin: Multipotential progenitor cell.
  • Epidemiology: There is an even male to female distribution. Median age at presentation age 8 years although adult presentations also have been reported.
  • Clinical features: The disease in some cases appears to associated with other mendelian disorders including probable Noonans syndrome, cerebellar ataxia\/atrophy, and Fanconis anemia (monosomy 7 is also common in non-familial cases of MDS\/ANLL arising in Fanconis anemia and other contitutional disorders). Cytopenias and myelodysplasia in non-leukemic family members is common.
  • Pathology: The pathology is typical of MDS and ANLL.

    • Treatment

    The number of reported cases makes it difficult to draw conclusions about appropriate therapy. Allogeneic transplantation from a related sibling is problematic because of the familial predisposition to hematologic malignancies.

    Prognosis

    The prognosis is poor. Nearly all reported patients have died of their disease.

    Cytogenetics

    Note

    Complete or partial monosomy may be associated with other abnormalities including +8, 5q-, and t(1;7). Of the 12 reported cases, the lost chromosome 7 was shown to be of different parental origin in two.

    Genes involved and Proteins

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    66380451983Familial leukemia and aplastic anemia associated with monosomy 7.Chitambar CR et al
    100867281999Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS).Hasle H et al
    48017111973Two autopsy cases of atypical myeloproliferative disorder with group C monosomy occurring in siblings.Kamiyama R et al
    106401522000Familial acute myeloid leukemia with monosomy 7: late onset and involvement of a multipotential progenitor cell.Kwong YL et al
    69478571981Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia.Li FP et al
    77188701995Childhood monosomy 7: epidemiology, biology, and mechanistic implications.Luna-Fineman S et al
    111729082001Familial partial monosomy 7 and myelodysplasia: different parental origin of the monosomy 7 suggests action of a mutator gene.Minelli A et al
    13587901992Evidence implicating heterozygous deletion of chromosome 7 in the pathogenesis of familial leukemia associated with monosomy 7.Shannon KM et al
    67332701984Transformation of Fanconi's anemia to acute nonlymphocytic leukemia associated with emergence of monosomy 7.Stivrins TJ et al