Genetics - general/chromosomal Flashcards
Choose the most appropriate diagnosis from the following options:
* Porphyria
* Farber disease
* Hunter syndrome
* Prolidase syndrome
* Hartnup disease
* Phenylketonuria
* Hurler syndrome
* Fabry disease
A child with a hoarse voice has swollen and painful joints. There are lipogranulomas under the skin.
Correct answer:Farber disease - ASAH1 gene
Explanation:
This is a classic description of Farber Disease, also known as Farber’s lipogranulomatosis (hoarse or weak cry, lipogranulomas and swollen, painful joints). Children may also have hepatosplenomegaly and developmental delay. Farber disease is a rare autosomal recessive condition caused by abnormal lipid metabolism. Lipids accumulate abnormally throughout the body, especially around the joints. Fabry Disease is a rare disorder that presents with neuropathic or limb pain with telangiectasias and angiokeratomas (usually affecting the groin and lower abdomen).
Choose the most appropriate diagnosis from the following options:
* Porphyria
* Farber disease
* Hunter syndrome
* Prolidase syndrome
* Hartnup disease
* Phenylketonuria
* Hurler syndrome
* Fabry disease
A child with a known diagnosis of mucopolysaccharidosis is noted to have melanocytic naevi.
Correct answer:Hurler syndrome - IUDA gene on chr4
Explanation:
Hurler syndrome (MPS I) is associated with melanocytic naevi. Melanocytic naevi are also associated with GM1 gangliosidosis type 1 but most commonly, melanocytic naevi occur in otherwise well children. Hunter syndrome (MPS II) is associated with the development of pearly papules.
Choose the most appropriate diagnosis from the following options:
* Porphyria
* Farber disease
* Hunter syndrome
* Prolidase syndrome
* Hartnup disease
* Phenylketonuria
* Hurler syndrome
* Fabry disease
A child with a known diagnosis of mucopolysaccharidosis is noted to have pearly papules.
Correct answer:Hunter syndrome - IDS gene
Explanation:
Hunter syndrome (MPS II) is associated with the development of pearly papules. Hurler syndrome (MPS I) is associated with melanocytic naevi. Melanocytic naevi are also associated with GM1 gangliosidosis type 1 but most commonly, melanocytic naevi occur in otherwise well children.
Choose the most appropriate diagnosis from the following options:
* Porphyria
* Farber disease
* Hunter syndrome
* Prolidase syndrome
* Hartnup disease
* Phenylketonuria
* Hurler syndrome
* Fabry disease
A child is poorly compliant with dietary treatment and presents with developmental delay, hypopigmentation and eczema.
Correct answer:Phenylketonuria - PAH gene
Explanation:
The textbook image of phenylketonuria is a blonde child with blue eyes, however children with classic PKU tend to just have lighter skin and hair than unaffected family members. They are also at increased risk of eczema, especially if not compliant with phenylalanine reduced diet
Gene associated with: CF
Autosomal recessive Cystic fibrosis conductance transmembrane regulator(CFTR); prevalence 1/2500
Gene associated with: sickle cell anaemia
Autosomal recessive Beta hemoglobin(HBB)
Gene associated with: albinism, oculocutaneous, type 2
Autosomal recessive Oculocutaneous albinism II(OCA2)
Gene associated with: Huntington’s disease
Autosomal dominant Huntingtin (HTT)
Gene associated with: myotonic dystrophy type 1
Autosomal dominant Dystrophia myotonica-protein kinase(DMPK)
Gene associated with: hypercholesterolaemia AD type B
Autosomal dominant Low-density lipoprotein receptor(LDLR);apolipoprotein B(APOB)
Gene associated with: NF type 1
Autosomal dominant Neurofibromin 1(NF1)
Gene associated with: NF type 2
Neurofibromin 2 (NF2)
Gene associated with: PKD type 1
Autosomal dominant Polycystic kidney disease 1(PKD1)
Gene associated with: PKD type 2
Autosomal dominant Polycystic kidney disease 2(PKD2)
Gene associated with: haemophilia A
X-linked recessive Coagulation factor VIII(F8)
Gene associated with: muscular dystrophy (Duchenne)
X-linked recessive Dystrophin(DMD)
Gene associated with: muscular dystrophy (Becker)
Gene associated with: Rett’s syndrome
X-linked dominant Methyl-CpG-bindingprotein2(MECP2)
Gene associated with: hypophosphatemic rickets, X linked dominant
X-linked dominant Phosphate-regulating endopeptidase homologue, X-linked(PHEX)
Gene associated with: Spermatogenic failure, non obstructive, Y linked
Y-linked Ubiquitin-specific peptidase 9Y, Y-linked(USP9Y)
Fragile X syndrome
X linked, trinucleotide repeat expansion, FMR1 gene
Friedreich’s ataxia
FRDA gene, trinucleotide repeat expansion disorder
spinocerebellar ataxia
SCA1, SCA 2, SCA3, ATXN1 genes; trinucleotide repeat expansion
Patau - genetics, prevalence, associations, prognosis
T13, 1/5000 liveborns, midline defects and normally grown (unlike Edwards); Median survival 10 days, 80% die by 3 months, 92% die by 1 year, Profound intellectual disability in survivors
Edward - genetics, prevalence, associations, prognosis
T18; 1/5500, relationship with AMA and 3:1 F:M; IUGR, horseshoe kidney, rocker bottom feet, fisted fingers, hypertonic, cardiac (>50%), GIT (>75%); Death within first 2 weeks = 50%, 3 months 80%, 12 months 90%
Down - genetics, prevalence, associations
T21; 1/800, relationship with AMA, trisomy then translocation then mosaic; cardiac 50% (AVSD), hypotonia, poor moro, OA axial instability, transient leukaemia/AMKL, AML, duodenal atresia (12%)
Klinefelter - genetics, prevalence, associations, prognosis
47 XXY, 1/600 males, normal phenotype and go unrecognized for life OR learning difficulty in childhood OR delayed puberty at adolescence OR infertility as adult; primary hypogonadism, gynaecomastia, small testes, low libido, normal intelligence but reduce IQ behavioural phenotype, 55% MV prolapse, tall stature w long legs and long arms, eunuchoid body habitus; Increased morbidity in later life from pulmonary diseases, cancers (including breast), diabetes, SLE (extra X chromosome)
Turner - genetics, prevalence, associations, prognosis
45 XO; 1/5000 (most spont abort), monosomy (45%) or mosaicism (50%); Short stature (95-100%) Growth failure (90-95%) Infertility (95%) Ovarian failure (90%) Increased upper: lower segment (>90%) Defective dental development (75%) Recurrent otitis media (50-70%) SNHL (50% by adulthood) Cardiac malformations - long transverse aortic arch, aortic root dilatation, bicuspid aortic valve, coarctation (50%); Often in neonatal period presents with oedema of hands/feet, resolves by 2 years but an recur at any age; 7. Complications: ↑ risk of autoimmune problems (hypothyroidism, coeliac disease), risk of aortic dissection
Isochromosome X
Isochromosome for the long arm of the X chromosome (isoXq) = the short arm (p) is deleted and replaced with an exact copy of the long arm (q). One of the most common structural sex chromosome abnormalities. Not associated with increased paternal age
Jacobs syndrome
47 XYY, 1/1000; Tall stature, mild delay in motor and language, normal puberty + fertility. NO increase in aggression
Metafemale syndrome
47 XXX; Most common sex chromosome abnormality in females; Usually incidental diagnosis; May have slightly lower IQ 15-30 than siblings
48 XXYY
- Tall with adult height >6 feet
- Eunuchoid habitus – long legs, sparse body hair
- Small testicles and penis
- Hypergonadotropic hypogonadism + gynaecomastia
- IQ 60-80 – delayed speech
48 XXXY
- Average or tall stature
- Ocular hypertelorism, flat nasal bridge, radioulnar synostosis, fifth-finger clinodactyly
- Small penis and testicles
- IQ 40-60 – severely delayed speech
