Familial Monosomy 7 Syndrome

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.
Other names	Familial leukemia or MDS associated with monosomy 7
Inheritance	In some pedigrees the pattern of involvement is compatible with an autosomal dominant inheritance pattern with incomplete penetrance.

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 Noonan's syndrome, cerebellar ataxia/atrophy, and Fanconi's anemia (monosomy 7 is also common in non-familial cases of MDS/ANLL arising in Fanconi's 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

Note

The available data suggest that the monosomy 7 contributes to oncogenesis by reduced gene dosage. Studies showing different parental origin of the deleted chromosome argue against a possible tumor suppressor mutated on the retained chromosome. It has been proposed that the susceptibility locus or loci located on other chromosomes acts as a mutator that promotes chromosomal instability. In some pedigrees the pattern of involvement is compatible with an autosomal dominant inheritance pattern with incomplete penetrance.

Bibliography

Two autopsy cases of atypical myeloproliferative disorder with group C monosomy occurring in siblings.

Kamiyama R, Shibata T, Mori W

Acta pathologica japonica. 1973 ; 23 (4) : 815-835.

PMID 4801711

Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia.

Li FP, Hecht F, Kaiser-McCaw B, Baranko PV, Potter NU

Cancer genetics and cytogenetics. 1981 ; 4 (3) : 189-196.

PMID 6947857

Familial leukemia and aplastic anemia associated with monosomy 7.

Chitambar CR, Robinson WA, Glode LM

The American journal of medicine. 1983 ; 75 (5) : 756-762.

PMID 6638045

Transformation of Fanconi's anemia to acute nonlymphocytic leukemia associated with emergence of monosomy 7.

Stivrins TJ, Davis RB, Sanger W, Fritz J, Purtilo DT

Blood. 1984 ; 64 (1) : 173-176.

PMID 6733270

Familial bone marrow monosomy 7. Evidence that the predisposing locus is not on the long arm of chromosome 7.

Shannon KM, Turhan AG, Chang SS, Bowcock AM, Rogers PC, Carroll WL, Cowan MJ, Glader BE, Eaves CJ, Eaves AC

The Journal of clinical investigation. 1989 ; 84 (3) : 984-989.

PMID 2569483

Evidence implicating heterozygous deletion of chromosome 7 in the pathogenesis of familial leukemia associated with monosomy 7.

Shannon KM, Turhan AG, Rogers PC, Kan YW

Genomics. 1992 ; 14 (1) : 121-125.

PMID 1358790

Childhood monosomy 7: epidemiology, biology, and mechanistic implications.

Luna-Fineman S, Shannon KM, Lange BJ

Blood. 1995 ; 85 (8) : 1985-1999.

PMID 7718870

Myelodysplastic 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, Aricˆ¾ M, Basso G, Biondi A, Cantˆ¼ Rajnoldi A, Creutzig U, Fenu S, Fonatsch C, Haas OA, Harbott J, Kardos G, Kerndrup G, Mann G, Niemeyer CM, Ptoszkova H, Ritter J, Slater R, Starˆ‡ J, Stollmann-Gibbels B, Testi AM, van Wering ER, Zimmermann M

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 ; 13 (3) : 376-385.

PMID 10086728

Familial acute myeloid leukemia with monosomy 7: late onset and involvement of a multipotential progenitor cell.

Kwong YL, Ng MH, Ma SK

Cancer genetics and cytogenetics. 2000 ; 116 (2) : 170-173.

PMID 10640152

Familial partial monosomy 7 and myelodysplasia: different parental origin of the monosomy 7 suggests action of a mutator gene.

Minelli A, Maserati E, Giudici G, Tosi S, Olivieri C, Bonvini L, De Filippi P, Biondi A, Lo Curto F, Pasquali F, Danesino C

Cancer genetics and cytogenetics. 2001 ; 124 (2) : 147-151.

PMID 11172908

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Contributor(s)

Written	07-2001	Jay L. Hess

Citation

This paper should be referenced as such :

Hess JL . Familial Monosomy 7 Syndrome. Atlas Genet Cytogenet Oncol Haematol. July 2001 . URL : http://AtlasGeneticsOncology.org/Kprones/FamilMono7ID10059.html

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indexed on : Mon May 12 18:13:44 2008

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