T/F: aneuploidy syndrome means that the mutation is an inherited chromosomal disorder that is usually autosomal recessive
False; most is not inherited, the mutation occurs through nondisjunction during meiosis
Monosomy X refers to _____ syndrome, affecting ___ (gender)
Short stature syndromes:
Tuner (Monosomy X)
Albright hereditary osteodystrophy (ASO)
Turner syndrome chromosomal mutation is ______
Females with only one X chromosome
Clinical presentation of Monosomy X:
Wide spaced nipples
Heart and skeletal defects
What is the pseudoautosomal regions of X and Y chromosome?
PAR 1 and PAR 2
They behave like an autosome and recombine during meiosis, so genes in this region can be inherited in an autosomal rather than a strictly sex-linked fashion
Basically, genes in this region escape female X-inactivation, which is why Turner syndrome (Monosomy X) actually manifest clinically
What is the gene that is located in PAR 1 that contributes to Turner Syndrome features?
SHOX (short stature homeobox-containing) – important in bone development and growth
Males have ____ (quantity) PAR gene(s), and females of _____ PAR gene(s). Those with Turner Syndrome have ______ gene(s)
1; haploinsufficiency of SHOX gene
T/F: Turner syndrome has excessive expression of SHOX, a gene located in PAR 1 on sex chromosomes
False; turner syndrome has haploinsufficiency SHOX (one missing; SHOX is responsible for bone development and growth). Klinefelter has an excessive expression of SHOX, as there at least an extra X chromosome there
Tall stature syndromes:
Klinefelter syndrome (XXY)
Beckwith-Wiedemann Syndrome (BWS)
Klinefelter is a(n) _____ chromosomal condition with karyotype _____, affecting ______, resulting in ____ stature.
Which chromosomal condition results in males with feminine body pattern, i.e: broad hips, narrow shoulders, sparse body hair, gynecomastia
Klinefelter syndrome (XXY).
Also small testes, absent spermatogenesis, androgen deficiency, obesity, diabetes and autoimmune disorders
T/F: Extra X chromosomes in Klinefelter syndrome derives equally from paternal or maternal gamete that formed the individual
SHOX haploinsufficiency is seen in ____ syndrome, excessive SHOX is seen in _____ syndrome
Turner (short stature)
Klinefelter (tall stature)
T/F: Noonan syndrome is X-linked recessive when inherited, but most are de novo
False; noonan when inherited is Autosomal DOMINANT, but it’s true that most are de novo
Which syndrome could lead to critical congenital heart disease, bleeding disorder, and children with 8-fold increase risk of leukemia or other cancer?
T/F: like Turner’s, Noonan syndrome is short stature seen in females, just this one is an Autosomal dominant condition instead of a chromosomal condition
False; Noonan can cause short stature in both males and females. It is Autosomal Dominant
Noonan syndrome is due to disruption of _____ signaling pathway in 70% of cases, causing ______ (length of) activation of the pathway.
RAS-MAPK (gain of function)
Prolonged activation of pathway
Which gene is mutated in 50% of Noonan syndrome and what is the name of the proto-oncogene that it encodes?
Mutations in PTPN11 which encodes SHP-2 (proto-oncogene)
Proto-Oncogene ______, which is encoded by ______, induces _____ (symptom) in half of Noonan syndrome cases
Growth retardation – which results in the short stature
T/F: Achondroplasia is an autosomal dominant disorder that results in small head and torso but regular long bone length
False; it is autosomal dominant, however it is short-limb dwarfism, which is short arms and legs (long-bones) but normal or enlarged head and normal torso
What is GNAS gene? In which condition is this gene mutated in causing short stature?
GNAS codes for G protein that helps regulate activity and production of certain hormones and regulating bone development
Loss-of-function mutation is seen in Albright hereditary osteodystrophy (ASO)
In Albright hereditary osteodystrophy, pseudo hypoparathyroidism type 1A is inherited from _______, pseudo pseudohypoparathyroidism (PPHP) is inherited from ______. Which one effects parathyroid an calcium level?
Mother – type 1A
Father – pseudo pseudo
Type 1A from mom results in the body not responding to parathyroid hormone causing low levels of calcium in bones and blood
Clinical presentation of Albright hereditary osteodystrophy?
Obesity (Michelin baby!)
Short fingers and toes
Absent 4th knuckles
Short 4th metacarpals
Which condition is a result from an imbalance in the expression of imprinted genes in the 11p15 region, leading to overgrowth?
Beckwith-Widemann syndrome clinical presentation:
Large infant, larger than peer during childhood
Some children with opening in the wall of the abdomen that lets the organs to protrude through the belly-button
Abnormally large tongue (macroglossia)
Beckwith-Widemann syndrome have increased risk of which childhood cancers?
Wilms tumor (kidney)
Stature conditions that may lead to cancer?
Beckwith-Widemann (wilms tumor (kidney) or hepatoblastoma)
Noonan syndrome (leukemia)
T/F: Adults with Beckwith-Widemann are usually tall, probably half the people in the NBA have this
False; growth slows by age 8, and adults are generally no unusually tall
Abnormally large tongue, may interfere with breathing, swallowing and speaking, is seen in _____ syndrome
Beckwith-Widemann syndrome genetic defects is seen in ____ region: abnormal DNA methylation in this area, which leads to overactivity of _____ gene, a growth factor, and/or no active ____ gene or _____ gene which are tumor suppressor and growth suppressor, respectively
IGF2 (growth factor)
CDKN1C (tumor suppressor)
H19 (growth suppressor)
Genes that are affected in Beckwith-Widemann syndrome, which is from paternal allele, and which is from maternal allele?
IGF 2 from paternal allele – promote growth
H19 and CDKN1C from maternal – constrains growth (these are the gene that are not active in this condition)
Scoliotic person with flexible joints, tall stature, thin, and dislocated lens in eyes and a bad heart (mitral valve prolapse and aortic aneurysm), most probably have _______ syndrome
Inheritance pattern for Marfan is ________
What is mutated in Marfan syndrome?
Fibrilin gene (FBN1) resulting in abnormal connective tissue
T/F: Marfan syndrome is gain of function mutation in FGFR3, resulting in increased bone growth
False false false! Marfan is mutation in fibrilin gene FBN1, which results in abnormal CONNECTIVE TISSUE, NOT BONE!
FGFR3 mutation is achondroplasia
Mutations in: FGFR3 is ______, PTPN11 is _______, GNAS is ______, FBN1 is ________
Albright hereditary osteodystrophy
Increased in MAPK pathway is ______ and _______.
Achondroplasia and noonan
Turner syndrome related heart defect:
Coarctation of the aorta
Marfan related heart defect:
Mitral valve prolapse
Heart defect in Noonan:
Congenital heart Dz
T/F: Male patient with Klinefelters (XXY), is at increased risk for breast cancer
True; there are more breast tissue in Klinefelter patients than normal males