Monosomy 7, or deletion of part of chromosome 7, is seen in myelodysplastic syndromes and acute myeloid leukemia. It is the most common chromosomal abnormality in secondary AML cases following chemotherapy or radiation exposure. Monosomy 7 occurs in about 5% of de novo and 40% of secondary AML cases. The deletion of certain genes on chromosome 7 appears to be important in the development of myelodysplasia.

2. Monosomy 7
 Monosomy 7 or partial deletion of the long arm of chromosome 7 (7q-) is a
frequent cytogenetic finding in the bone marrow of patients with
myelodysplasia (MDS) and acute myelogenous leukemia (AML).
 Furthermore, monosomy 7 or 7q- is the most frequent abnormality of
karyotype in cases of AML that occur after cytotoxic cancer therapy or
occupational exposure to mutagens.
 The age distribution of de novo cases shows peaks in the first and fifth
decades. Monosomy 7 is found in about 5% of de novo and 40% of secondary
cases of AML. These findings suggest that loss of certain genes at this region is
an important event in the development of myelodysplasia

3. Causes
 In individuals with Chromosome 7, there is deletion
(monosomy) of a portion of the short arm (p) of
chromosome 7.
 In most cases, Chromosome 7, Partial Monosomy 7p
appears to be caused by spontaneous (de novo)
errors during early embryonic development that
occur for unknown reasons.
In such instances, the parents of the affected child
usually have normal chromosomes and a relatively
low risk of having another child with the
chromosomal abnormality.

4. Causes
 Rare cases have also been reported that appear to result
from balanced chromosomal rearrangements in one of the
parents.
Such a chromosomal rearrangement may be associated with an
increased risk of abnormal chromosomal development in the
carrier’s offspring.
 Chromosomal analysis and genetic counseling are typically
recommended for parents of an affected child to help
confirm or exclude the presence of a balanced chromosomal
rearrangement involving chromosome 7 in one of the
parents.

5. Signs & symptoms
 Patients can be asymptomatic or, if anemia is more severe, can have
pallor, weakness, loss of a sense of well being, and exertional
dyspnea.
 A small proportion of patients have infections related to severe
neutropenia or neutrophil dysfunction, or hemorrhage related to
severe thrombocytopenia or platelet dysfunction at the time of
diagnosis.
 Patients with severe depressions of neutrophil and platelet counts at
diagnosis usually have oligoblastic myelogenous leukemia.
 Rarely, patients have fever unrelated to infection.
 Arthralgia is the initial complaint in some patients.
 The presentation, infrequently, can mimic a connective tissue
disease.
 Hepatomegaly or splenomegaly occurs in approximately 5 or 10
percent of patients, respectively.

6. Special Clinical Features of
Myelodysplastic Syndromes
 Diabetes Insipidus of Myelodysplastic Syndromes
Patients with an indolent phase (oligoblastic myelogenous
leukemia) prior to overt AML may develop diabetes
insipidus. Hypothalamic involvement can lead to polyuria,
polydipsia, and decreased libido. Hypothalamic-posterior
hypophysis insufficiency in clonal myeloid states is
associated with monosomy 7 in hematopoietic cells.
 Neutrophilic Dermatosis of Myelodysplastic Syndromes
Acute neutrophilic dermatosis (Sweet disease) is an acute
febrile illness characterized by erythematous patches on
the arms, face, and legs that progress to painful brown
plaques. The plaques may ulcerate and produce large
necrotizing skin lesions.

7. Special Clinical Features of
Myelodysplastic Syndromes
 Inflammatory Syndromes of Myelodysplastic Syndromes
Immune or inflammatory syndromes may be seen in as many
as 10 percent of patients.
A symptom complex that mimics systemic lupus
erythematosus; fever, pleurisy, symmetric arthritis, plasma
antinuclear antibody, and pancytopenia.
Behçet disease, glomerulonephritis, seronegative arthritis,
systemic vasculitis, polychondritis, polyneuropathy,
panniculitis, and inflammatory bowel disease also have
been associated with clonal myeloid disorders.
 Other Cancers of Myelodysplastic Syndromes
The incidence of other cancers may be higher in subjects
with myelodysplastic diseases.

8. Diagnosis
 the diagnosis of Chromosome 7, Partial Monosomy 7p may be suggested
before birth (prenatally) by specialized tests such as ultrasound,
amniocentesis, and/or chorionic villus sampling (CVS).
 During fetal ultrasonography, reflected sound waves create an image of the
developing fetus, potentially revealing certain characteristic findings that
suggest a chromosomal disorder or other abnormalities.
 With amniocentesis, a sample of fluid that surrounds the developing fetus is
removed and analyzed,
 while CVS involves the removal of tissue samples from a portion of the
placenta. Chromosomal analysis performed on such fluid or tissue samples
may reveal the presence of Partial Monosomy 7p.

9. Diagnosis
 The syndrome may be diagnosed and/or confirmed after birth (postnatally) by
a thorough clinical evaluation, identification of characteristic physical
findings, and chromosomal analysis. Diagnostic evaluation may include various
studies, including advanced imaging techniques, to help detect and/or
characterize certain abnormalities that may be associated with the syndrome
(e.g., particular craniofacial defects, musculoskeletal abnormalities, etc.).
 In addition, a thorough cardiac evaluation may be advised to detect any heart
abnormalities that may be present. Such evaluation may include a thorough
clinical examination, evaluation of heart and lung sounds through
use of a stethoscope.
 and specialized tests that enable physicians to evaluate the structure and
function of the heart (e.g., x-ray studies, electrocardiography [EKG],
echocardiography).

10. Management
 Definitive therapy is bone marrow transplantation (BMT)
prior to the emergence of a leukemic clone.
 The suitability of sibs who are potential bone marrow
donors may be evaluated with appropriate hematologic
and cytogenetic studies to rule out bone marrow disease
associated with familial monosomy 7.
 However, given that the underlying germline pathogenic
variant may not be known, a matched sib donor may not
be an ideal candidate (unless much older than the
affected individual and with no evidence of hematologic
disorders )
 An unrelated donor may be more suitable

11. Prevention of Secondary
Complications
Individuals with monosomy 7 have increased
sensitivity to chemotherapy and radiation doses
used in conventional ablative BMT approaches,
and therefore require reduction in conditioning
intensity.

12. Molecular Genetics
 Heterozygous microdeletion
involved 3 contiguous
genes, SAMD9 (sterile alpha
motif domain containing 9)
, SAMD9L (sterile alpha
motif domain containing 9
like) , and HEPACAM2 .
o These 3 genes deleted at
high frequency in both adult
and childhood myeloid
leukemia.

13. Molecular Genetics
 Heterozygous acquired deletions
at EZH2 (enhancer of zeste 2
polycomb repressive complex 2
subunit) and CUL1 (Cullin 1)
genes in bone marrow cells
o The findings suggested that EZH2
may act as a tumor suppressor
gene in some cases, and likely
influences epigenetic
modifications that may lead to
cancer, since EZH2 functions as a
histone methyltransferase.

14. Mode of Inheritance
 The mode of inheritance of familial monosomy 7
is unclear.
 Because parents of these probands do not appear
to be affected, autosomal recessive inheritance
has been suggested . However, there is no report
of relationships between the fathers of these
kindreds, making autosomal recessive inheritance
less likely.

15. Mode of Inheritance
 In one kindred, eight of 14 first cousins (the offspring of 3
sisters) developed aplastic anemia or acute myeloid
leukemia (AML). Thus, in this family approximately 50% of
maternal first cousins inherited a trait that resulted in
aplastic anemia or AML with frequent loss of chromosome
7.
 Another kindred with five maternally related first cousins
from two sibships shows a similar pattern of inheritance.
 In both of these kindreds, male and female cousins were
affected, suggesting that this is not an X-linked trait.

16. Related Genetic
Counseling Issues
 Family planning
o The optimal time for estimating genetic risk is before pregnancy.
o It is appropriate to offer genetic counseling to young adults who
are affected or at risk.
 DNA banking is the storage of DNA (extracted from WBCs) for
possible future use.
o Because it is likely that testing methodology (e.g. genome
sequencing) and our understanding of genes, allelic variants, and
diseases will improve in the future
o Consideration should be given to banking DNA of affected individual
and their family members.