CMN 577 HIV Study Guide Question Graded A+
Down Syndrome - Labs & Imaging - Multiple Marker Screening (MMS) - also known as the triple screen-
may be performed between 15 and 20 weeks of gestation. This evaluates for Down Syndrome, neural
tube defects (such as spina bifida and anencephaly), multiple fetuses, and to evaluate the pregnancy
timeline or progression (is it as far along as it should be). The test evaluates alpha-fetoprotein (AFP),
hCG, and estriol. Elevated levels of of AFP are associated with neural tube defects. Abnormal AFP levels
raise concerns for trisomy disorders such as Down Syndrome (low AFP) and Trisomy 18 (low AFP). Low
estriol is found in both Down Syndrome and Trisomy 18. Inhibin A is elevated in Trisomy 21 and is
normal in Trisomy 18. Further confirmatory testing, including amniocentesis, is needed.
Cytogenomic analysis should be performed to look for unbalanced translocations. A parent with
balanced translocations (an even/equal exchange of genetic material that allows for full functionality
without extra or missing information) has a higher risk of having additional children with Down
Syndrome.
Down Syndrome - Treatment - Surgery as indicated for congenital defects- patients typically do well with
this type of intervention. Monitor for hypothyroidism, symptoms of dementia (early or late), and for
leukemia. Patients with Down Syndrome have a higher childhood risk for acute lymphoblastic and
myeloid leukemias. There may be an impairment of the immune system, therefore increasing the risk for
infection(s). Celiac disease and atlanto-axial instability (remember your M/S unit last semester?) are also
possible complications that should be monitored.
Fragile X - Overview - This genetic disorder has the highest number of mental retardation cases in males
other than Down Syndrome. The incidence, according to Hay 23rd edition, is approximately 1 in 1000
males. (Interesting note- Papadakis and McPhee, 2018, states the rate is 1 in 4000 males p. 1693). The
occurrence in females is approximately 50% less than males.
The FMR1 gene has expanded trinucleotide repetition with more than 200 copies being present.
Fragile X - S/S - Males: mental retardation, autism spectrum disorders along with impulsivity, repetitive
and aggressive behaviors. After puberty, the testes are enlarged (macro-orchidism). Other physical
findings include large ears, a more prominent jaw, and high pitched voice.
Females: the only physical signs are early menopause (ovarian failure). Mental retardation may be
present but learning disabilities, and sensory issues (think of the autism spectrum).
If there is moderate trinucleotide repetition (55 to 200 copies), the patient is a permutation carrier. In
females there is a higher risk for premature menopause as well as mild cognitive impairment. Both
males and females are subject to mood disorders, including anxiety, as well as tremor and ataxia after
middle age.
,Fragile X - Labs & Imaging - Evaluation for the number of trinucleotide repeats near the FMR1 gene
should be done on any male or female with unexplained mental retardation. Everyone has some repeats
but the higher the number (past 52), the greater the chances of passing this onto future generations if
reproduction occurs.
Fragile X - Treatment - Symptomatic treatment of behaviors along with supportive care, counseling, and
educational assistance as indicated.
Klinefelter Syndrome - Overview - Klinefelter Syndrome is associated with the 47,XXY karyotype; males
have an extra X chromosome. It is estimated that Klinefelter Syndrome affects 1 in 660 males but is
often not discovered (or diagnosed) until the male is evaluated for infertility issues.
Klinefelter Syndrome - S/S - After puberty, symptoms include height greater than their peers (long arms
and legs that are disproportionate to their body), small testes, gynecomastia, sparse body hair, and a
female escutcheon (pubic hair growth pattern- female being flat topped rather than a peak towards the
umbilicus).
Infertility is due to azoospermia.
Klinefelter Syndrome - Labs & Imaging - Evaluate for low serum testosterone and glucose intolerance.
Monitor for symptoms of deep vein thromboses and for breast cancer symptoms.
Klinefelter Syndrome - Treatment - Testosterone replacement will help with sex drive, erectile
dysfunction, and somewhat with depressive symptoms, etc. It will not reverse the infertility issue but
there have been cases where the mature sperm are aspirated from the testes. The sperm are then used
to fertilize oocytes, which are then implanted into the female partner's uterus. Genotyping is advised
prior to this procedure in order to reduce the risk of further genetic defects. Aneuploidy is the term used
in Papadakis and McPhee (2018)- it is defined as an error in cell division, resulting in the wrong number
of chromosomes.
Neurofibromatosis Type 1 - Overview - There are actually 2 forms of neurofibromatosis recognized, Type
1 (Recklinghausen disease) and Type 2.
Neurofibromatosis Type 1 - S/S - Spinal and cranial nerves are typically affected, especially the 8th
cranial nerve. There are usually multiple neurofibromas present, consisting of palpable, mobile nodules.
Café au lait spots are considered cutaneous lesions. Multiple hyperpigmented macules, Lisch nodules,
and neurofibromas as well as mutations on chromosome 17 are consistent with Neurofibromatosis Type
, 1. Lisch nodules are dome shaped gelatinous masses that develop on the surface of the iris and are a
common symptom of NF 1. These may grow to be as large as 2 mm in diameter.
Marfan Syndrome - Overview - Mutation or alteration of the Fibrillin-1 gene
Arachnodactyly - Unusually long fingers and toes
Hypermobility of the joints
Enlarged hands, very tall, flat feet
Eye abnormalities
High-arched palate
Scoliosis- as much as 60% of diagnosed patients
Cardiac Involvement - Up to 90% have cardiac disorders, Thoracic aortic aneurysm - dissection, Aortic
and or Mitral valvular disorders
Marfan Syndrome - S/S - Unusually tall, with long arms and legs along with arachnodactyly (long digits).
Patients with Marfan Syndrome have scoliosis, anterior chest wall deformity, and frequently, mitral
valve prolapse. Aortic root dilatation may lead to aortic regurgitation or aortic dissection and rupture.
Ophthalmologic disorders include severe myopia as well as ectopia lentis (displacement of the lens of
the eye) in about half of the patients with Marfan Syndrome.
Marfan Syndrome - Labs & Imaging - There is not a specific, diagnostic lab test to definitively diagnosis
Marfan Syndrome. There are mutations in the fibrillin gene (FBN1) on chromosome 15 but this can be
associated with other issues as well.
Marfan Syndrome - Diagnosis - The diagnostic criteria is known as the Ghent Nosology; this was refined
in 2010 and the new diagnostic criteria is known as: The 2010 Revised Ghent Nosology. (I know, catchy
right?). Here is the revised diagnostic criteria taken from the Marfan Syndrome website
(https://www.marfan.org/dx/rules)
** Please note... The two cardinal features are ectopia lentis and aortic root dilatation. **
Marfan Syndrome - Treatment - Annual ophthalmologic evaluations should be conducted in order to
correct the vision deficits as well as to prevent amblyopia. Orthopedic evaluations should be ordered to
evaluate and treat scoliosis. An annual echocardiogram should be performed to monitor the aortic
diameter and valve function (in particular, the mitral valve). Atenolol has proven helpful in slowing the
aortic dilatation - dosing is based on weight with 1-2 mg/kg per day being the goal. Angiotensin receptor
Down Syndrome - Labs & Imaging - Multiple Marker Screening (MMS) - also known as the triple screen-
may be performed between 15 and 20 weeks of gestation. This evaluates for Down Syndrome, neural
tube defects (such as spina bifida and anencephaly), multiple fetuses, and to evaluate the pregnancy
timeline or progression (is it as far along as it should be). The test evaluates alpha-fetoprotein (AFP),
hCG, and estriol. Elevated levels of of AFP are associated with neural tube defects. Abnormal AFP levels
raise concerns for trisomy disorders such as Down Syndrome (low AFP) and Trisomy 18 (low AFP). Low
estriol is found in both Down Syndrome and Trisomy 18. Inhibin A is elevated in Trisomy 21 and is
normal in Trisomy 18. Further confirmatory testing, including amniocentesis, is needed.
Cytogenomic analysis should be performed to look for unbalanced translocations. A parent with
balanced translocations (an even/equal exchange of genetic material that allows for full functionality
without extra or missing information) has a higher risk of having additional children with Down
Syndrome.
Down Syndrome - Treatment - Surgery as indicated for congenital defects- patients typically do well with
this type of intervention. Monitor for hypothyroidism, symptoms of dementia (early or late), and for
leukemia. Patients with Down Syndrome have a higher childhood risk for acute lymphoblastic and
myeloid leukemias. There may be an impairment of the immune system, therefore increasing the risk for
infection(s). Celiac disease and atlanto-axial instability (remember your M/S unit last semester?) are also
possible complications that should be monitored.
Fragile X - Overview - This genetic disorder has the highest number of mental retardation cases in males
other than Down Syndrome. The incidence, according to Hay 23rd edition, is approximately 1 in 1000
males. (Interesting note- Papadakis and McPhee, 2018, states the rate is 1 in 4000 males p. 1693). The
occurrence in females is approximately 50% less than males.
The FMR1 gene has expanded trinucleotide repetition with more than 200 copies being present.
Fragile X - S/S - Males: mental retardation, autism spectrum disorders along with impulsivity, repetitive
and aggressive behaviors. After puberty, the testes are enlarged (macro-orchidism). Other physical
findings include large ears, a more prominent jaw, and high pitched voice.
Females: the only physical signs are early menopause (ovarian failure). Mental retardation may be
present but learning disabilities, and sensory issues (think of the autism spectrum).
If there is moderate trinucleotide repetition (55 to 200 copies), the patient is a permutation carrier. In
females there is a higher risk for premature menopause as well as mild cognitive impairment. Both
males and females are subject to mood disorders, including anxiety, as well as tremor and ataxia after
middle age.
,Fragile X - Labs & Imaging - Evaluation for the number of trinucleotide repeats near the FMR1 gene
should be done on any male or female with unexplained mental retardation. Everyone has some repeats
but the higher the number (past 52), the greater the chances of passing this onto future generations if
reproduction occurs.
Fragile X - Treatment - Symptomatic treatment of behaviors along with supportive care, counseling, and
educational assistance as indicated.
Klinefelter Syndrome - Overview - Klinefelter Syndrome is associated with the 47,XXY karyotype; males
have an extra X chromosome. It is estimated that Klinefelter Syndrome affects 1 in 660 males but is
often not discovered (or diagnosed) until the male is evaluated for infertility issues.
Klinefelter Syndrome - S/S - After puberty, symptoms include height greater than their peers (long arms
and legs that are disproportionate to their body), small testes, gynecomastia, sparse body hair, and a
female escutcheon (pubic hair growth pattern- female being flat topped rather than a peak towards the
umbilicus).
Infertility is due to azoospermia.
Klinefelter Syndrome - Labs & Imaging - Evaluate for low serum testosterone and glucose intolerance.
Monitor for symptoms of deep vein thromboses and for breast cancer symptoms.
Klinefelter Syndrome - Treatment - Testosterone replacement will help with sex drive, erectile
dysfunction, and somewhat with depressive symptoms, etc. It will not reverse the infertility issue but
there have been cases where the mature sperm are aspirated from the testes. The sperm are then used
to fertilize oocytes, which are then implanted into the female partner's uterus. Genotyping is advised
prior to this procedure in order to reduce the risk of further genetic defects. Aneuploidy is the term used
in Papadakis and McPhee (2018)- it is defined as an error in cell division, resulting in the wrong number
of chromosomes.
Neurofibromatosis Type 1 - Overview - There are actually 2 forms of neurofibromatosis recognized, Type
1 (Recklinghausen disease) and Type 2.
Neurofibromatosis Type 1 - S/S - Spinal and cranial nerves are typically affected, especially the 8th
cranial nerve. There are usually multiple neurofibromas present, consisting of palpable, mobile nodules.
Café au lait spots are considered cutaneous lesions. Multiple hyperpigmented macules, Lisch nodules,
and neurofibromas as well as mutations on chromosome 17 are consistent with Neurofibromatosis Type
, 1. Lisch nodules are dome shaped gelatinous masses that develop on the surface of the iris and are a
common symptom of NF 1. These may grow to be as large as 2 mm in diameter.
Marfan Syndrome - Overview - Mutation or alteration of the Fibrillin-1 gene
Arachnodactyly - Unusually long fingers and toes
Hypermobility of the joints
Enlarged hands, very tall, flat feet
Eye abnormalities
High-arched palate
Scoliosis- as much as 60% of diagnosed patients
Cardiac Involvement - Up to 90% have cardiac disorders, Thoracic aortic aneurysm - dissection, Aortic
and or Mitral valvular disorders
Marfan Syndrome - S/S - Unusually tall, with long arms and legs along with arachnodactyly (long digits).
Patients with Marfan Syndrome have scoliosis, anterior chest wall deformity, and frequently, mitral
valve prolapse. Aortic root dilatation may lead to aortic regurgitation or aortic dissection and rupture.
Ophthalmologic disorders include severe myopia as well as ectopia lentis (displacement of the lens of
the eye) in about half of the patients with Marfan Syndrome.
Marfan Syndrome - Labs & Imaging - There is not a specific, diagnostic lab test to definitively diagnosis
Marfan Syndrome. There are mutations in the fibrillin gene (FBN1) on chromosome 15 but this can be
associated with other issues as well.
Marfan Syndrome - Diagnosis - The diagnostic criteria is known as the Ghent Nosology; this was refined
in 2010 and the new diagnostic criteria is known as: The 2010 Revised Ghent Nosology. (I know, catchy
right?). Here is the revised diagnostic criteria taken from the Marfan Syndrome website
(https://www.marfan.org/dx/rules)
** Please note... The two cardinal features are ectopia lentis and aortic root dilatation. **
Marfan Syndrome - Treatment - Annual ophthalmologic evaluations should be conducted in order to
correct the vision deficits as well as to prevent amblyopia. Orthopedic evaluations should be ordered to
evaluate and treat scoliosis. An annual echocardiogram should be performed to monitor the aortic
diameter and valve function (in particular, the mitral valve). Atenolol has proven helpful in slowing the
aortic dilatation - dosing is based on weight with 1-2 mg/kg per day being the goal. Angiotensin receptor
