Genetics Diseases For Biochem Nbme

Front 1

Cri-du-chat syndrome

Back 1

Congenital microdeletion of short arm of
chromosome 5 (46,XX or XY, 5p-).

Findings: microcephaly, moderate to
severe intellectual disability, high-pitched
crying/mewing, epicanthal folds, cardiac
abnormalities (VSD).

Cri du chat = cry of the cat.

Front 2

von Hippel-Lindau disease

Back 2

Cavernous hemangiomas in skin, mucosa, organs; bilateral renal cell carcinomas;
hemangioblastoma (high vascularity with hyperchromatic nuclei G) in retina, brain stem,
cerebellum H; and pheochromocytomas. Autosomal dominant; mutated VHL tumor suppressorgene on chromosome 3, which results in constitutive expression of HIF (transcription factor) and
activation of angiogenic growth factors.

Front 3

Fragile X syndrome

Back 3

X-linked defect affecting the methylation and
expression of the FMR1 gene. The 2nd most
common cause of genetic intellectual disability
(after Down syndrome).

Findings: postpubertal macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse.

Trinucleotide repeat disorder (CGG)n.

Fragile X = eXtra large testes, jaw, ears.

Front 4

Phenylketonuria

Back 4

Due to decrease phenylalanine hydroxylase or decrease tetrahydrobiopterin cofactor (malignantPKU). Tyrosine becomes essential.
Increase phenylalanine leads to excess phenylketones in urine.

Findings: intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor.

Treatment: decrease phenylalanine and increase tyrosine in diet.

Autosomal recessive. Incidence ≈ 1:10,000.
Screened for 2–3 days after birth (normal at birth because of maternal enzyme during fetal
life).

PKU patients must avoid the artificial sweetener aspartame, which contains phenylalanine.

Front 5

Huntington Disease

Back 5

“Hunting 4 food.”

Findings:

depression,

progressive dementia,

choreiform movements,

caudate atrophy, and levels of GABA and ACh in the brain. Gene on chromosome 4;

trinucleotide repeat disorder: (CAG)n. repeats age of onset.

Alteration of gene expression in Huntington disease is believed to occur due to hyper methylation of histones. Hyper methylated histones bind DNA and prevent its transcription leading to disruption of synthesis of some neurotrophic proteins.

Front 6

Osteogenesis imperfect

Back 6

Genetic bone disorder (brittle bone disease)
caused by a variety of gene defects.
Most common form is autosomal dominant with decrease production of otherwise normal type I
collagen. OI manifestations can include:
Multiple fractures with minimal trauma
Blue sclerae B due to the translucency of the connective tissue over the choroidal
Veins
Hearing loss (abnormal ossicles)
Dental imperfections due to lack of dentin

Front 7

Prader-Willi syndrome

Back 7

Maternal imprinting: gene from mom is
normally silent and Paternal gene is deleted/
mutated. Results in hyperphagia, obesity,
intellectual disability, hypogonadism, and
hypotonia.

Front 8

AngelMan syndrome

Back 8

Paternal imprinting: gene from dad is normally
silent and Maternal gene is deleted/mutated.
Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe
intellectual disability

Front 9

Down syndrome

Back 9

(trisomy 21), 1:700
Drinking age (21).

Findings: intellectual disability, flat face,
prominent epicanthal folds, single palmar
crease, gap between 1st 2 toes, duodenal
atresia, congenital heart disease, Brushfield spots (spots in the eye).

Associated with risk of ALL, AML, and
Alzheimer disease (>35 years old).

95%of cases due to meiotic nondisjunction of
homologous chromosomes (associated with
advanced maternal age; from 1:1500 in women
>20 to 1:25 in women >45 years old).

Front 10

Edwards syndrome

Back 10

Findings: severe intellectual disability, rockerbottom feet, micrognathia (small jaw), low-set Ears, clenched hands, prominent occiput,congenital heart disease.

Death usually occurs within 1 year of birth.

1. Face: micrognathia, microstomia, eye defects (microphthalmia, cataracts coloboma), low-set and malformed ears, prominent occiput. -Ears - Edwards

2. CNS: microcephaly, neural tube defects (eg, meningocele, anencephaly), holoprosencephaly, Arnold-Chiari malformation, severe mental retardation, delayed psychomotor development

3. Musculoskeletal: clenched hands with overlapping fingers (index finger overrides the middle finger and fifth finger overrides the fourth finger), rocker-bottom feet, short sternum, and hypertonia
4. Cardiac: ventricular septal defect, patent duct arterio

Front 11

Turner syndrome

Back 11

“Hugs and kisses” (XO) from Tina Turner.

[female] (XO)

Short stature (if untreated),

ovarian dysgenesis (streak ovary),

shield chest,

heat defect: bicuspid aortic valve, preductal coarctation

lymphatic defects result in webbed neck or cystic hygroma - fat in neck.

lymphedema in feet, hands),
horseshoe kidney B.

Most common cause of 1° amenorrhea. No Barr body.

Patients with Turner syndrome may have karyotype 45, XO (complete monosomy), 45X0/46XX (mosaicism), or 46XX (with partial deletion of one X chromosome). Mosaicism appears to account for a majority of cases of Turner syndrome.

Front 12

Klinefelter syndrome

Back 12

male] (XXY), 1:850

Testicular atrophy, eunuchoid body shape,
tall, long extremities, gynecomastia, female
hair distribution A. May present with
developmental delay. Presence of inactivated X
chromosome (Barr body). Common cause of
hypogonadism seen in infertility work-up