Genetics

Question 1

Who am I?

I pass away at 10 days. I was found to have a scalp defect, cleft palate, cardiac defect.

Answer 1

Trisomy 13:

• Midline defect = holoprosencephaly, scalp defect (hair growing over scalp), cleft lip/ palate, cardiac defect (usually lead to early death)
• Caused by non-dysjunction event
• If i survive i have severe intellectual disability
• Karyotype, Microarray, FISH

Question 2

Who am I?
I’m a delightful 2 year old you see in you clinic 6 monthly. I have delays in speech and motor, likely related to my hypotonia, and mild hearing impairment.
I had a rocky start to life with a VSD repair and duodenal atresia.
I have a number of specialists who manage my hypothyroidism, post VSD repair care and OSA.
I’m 18 x more likely to develop leukemia than other children my age.
I’m not expected to have an IQ higher than a 5 year old.
I’ll have Alzheimer’s by 50yrs.

Answer 2

Trisomy 21:

• 1 in 800
• Trisomy in 95% (non-dysjunction - adv mat age), Robertsonian translocation (unbalanced) 2.5%, mosaic 2.5%
• Karyotype, microarray, FISH
• Dysmorphism (upslanting palpabral fissures, epicanthal folds, small low set ears, flat nasal bridge, small brachycephalic head, saddle gap, small open mouth, tongue hanging out, short neck,
• Visual (cataracts, strabismus) + hearing impairment (sensorineural + conductive)
• Occipito-atlanto axial instability
• OSA
• Hypotonia
• Hypothyroidism
• VSD > endocardial cushioning > PDA > ASD> TOF
• GIT: Duodenal Atresia, Hirshsprung’s, TOF
• Leukemia 18 x ALL/AML, lower rates of solid tumours
• Intellectual disability
• Alzheimer’s by age 50 (APP gene (amyloid precursor on chromosome 21)
• Coeliac disease

Question 3

Who am I?
I’m a neonate in NICU who is post op from a repair of omphalocele. I was macrosomic and also difficulty maintaining normoglycaemia, have coarse facial features (large tongue), and was noted to have bigger arm and leg on one side.

Answer 3

Beckworh-Weidermann: Growth problem

• Chromosome 11p15 imprinting (lose maternal (50% of cases, Paternal UPD 11 in 20%) = paternal over-expression = growth promoting)
• IGF-2 gene (paternally expressed growth factor
• -> Macrosomia, macroglossia, hemi-hypertrophy
• Course facial features
• Ear creases and ear pits
• Organomegally
• Abdominal wall defect (omphalocele, umbilical hernia)
• Hypoglycaemia
• Naevus flammeus
• Tall stature
• Predisposed to malignancies: Wilm’s tumour, hepatoblastoma, rhabdomyosarcoma, neuroblastoma = Abdo US3/12 to age 8.
• Ix: Methylation testing 11p

Question 4

Who am I?
I pass away at 14 days, most with my condition pass away in first year of life or FDIU.
I have wizened facial features, rockerbottom feet and overlapping fingers and IUGR
No antenatal care.

Answer 4

Trisomy 18 (Edwards):
Rockerbottom feet
Wizened facial features
Overlapping fingers 
IUGR
Low PAPPA, estradiol, BHCG
Non-dysjunction event most common

Question 5

Who am I?
I’m a 5 year old boy who you are seeing in you clinic for short stature. His past medical history was significant for IUGR and low birth weight and review for a large head. You notice on exam he has a triangle shaped face and pointy ears.

Answer 5

Russel-Silver Syndrome:
Chromosome 11p15 imprinting (lose paternal = maternal over-expression = growth restricting (IGF-2 turned off))

1. IUGR/ BW below or equal to 2 SD from pop mean
2. Short stature/ post natal growth below or equal 2 SD
3. Macrocephally (sparing HC)
4. Classic facial features: Triangle face, pointy ears
5. Skeletal assymetry

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