18.03.37 Chromosome 14 Flashcards
Give three clinical features of mosaic chromosome 14.
1) Developmental delay including speech and language
2) Short stature
3) Asymmetrical growth
4) Abnormal skin pigmentation
5) Slight facial dysmorphism
When mosaic T14 is identified at CVS or amnio, what else should be considered?
CVS - usually CPM, but there is a risk of UPD14
AF - risk of foetal abnormalities, risk of UPD14
- due to trisomy rescue
How does UPD14 occur?
Trisomy rescue
Monosomy rescue
Gamete complementation
What else is paternal UPD14 syndrome known as? Give three clinical features.
WANG syndrome
1) Obstetric complications, including polyhydramnios
2) Low birth weight
3) Thoracic and abdominal wall defects
4) Small chest and bell-shaped ribcage - leading to underdeveloped lungs and respiratory issues.
5) Moderate-severe LD
6) Subtle dysmorphism
What else is maternal UPD14 syndrome known as? Give three clinical features.
TEMPLE syndrome 1) Pre-and post-natal growth retardation 2) Low to normal ID 3) Subtle dysmorpism Generally mild phenotype, may go undiagnosed.
Where is the critical region for the UPD14 phenotype. Which critical genes does it include?
14q23-qter
Pat - DLK1, DIO3 and RTL1
Mat - GTL2, PEG11, antisense RTL1
Give three features of r(14) syndrome.
Phenotype arises from loss of critical genes when ring forms. Almost all de novo. Seizures Mild-mod MR DD, including S+L Slow growth and short stature Repeated respiratory infections Microcephaly Subtle dysmorphism
What is the significance of a supernumery ring(14)
Variable phenotype: normal to severe.
Those seen in normal individuals are normally inherited
Has been identified in male infertility and a patient with Down syndrome.
Give three clinical features of the 14q11-22 deletion syndrome.
1) Developmental delay
2) Dysmorphic features - hypertelorism, epicanthic folds, small mouth, long philtrum.
3) Partial agenesis of the corpus callosum
4) Blindness
5) Hearing impairment
6) Seizures
7) Apnoea
Give three clinical features associated with 14q22-q23 deletion syndrome.
<1 in 1,000,000. All sporadic cases. Eldest patient is 19 years old.
1) Bilateral anophthalmia or microphthalmia
2) Cerebral manifestations involving hypothalamus or pituitary
3) Endocrine abnormalities due to pituitary abnormalities - can affect growth and kidneys
4) Short stature
5) Cleft lip and palate
6) Ear anomalies
7) Developmental delay
8) Epilepsy
Name any gene that is a candidate for the phenotype seen in 14q22-q23 deletion syndrome.
1) OTX2 and BMP4 HI predicted to contribute to eye abnormalities
2) BMP4 and SIX6 likely to be associated with pituitary abnormalities
4) SIX6 likely to contribute to ear and craniofacial features.
Give two features of the terminal 14q deletion syndrome; 14q32.2-q32.3.
Very rare. Features include:
1) Hypotonia
2) Single palmar crease
3) Feeding difficulties
4) Eyesight problems
5) ID
Three candidate genes in 250kb critical region: CRIP2, MTA1, TMEM121
Give two examples of single-gene disorders associated with chromosome 14.
1) FOXG1 syndrome (14q12) - all dn AD cases, LOF/deletions. Microcephaly, impaired development, severe brain abnormalities, severe ID. Associated with congenital Rett syndrome in males.
2) Alpha-1 antitrypisin deficiency (SERPINA1, AR, 14q32.13)
3) Leber congenital amaurosis/Cone-rod dystrophy (RPGRIP1, 14q11.2)
4) Hypertrophic cardiomyopathy (MYH7, 14q11.2)
Give two features of the terminal 14q deletion syndrome; 14q32.2-q32.3.
Very rare. Features include:
1) Hypotonia
2) Single palmar crease
3) Feeding difficulties
4) Eyesight problems
5) ID
Three candidate genes in 250kb critical region: CRIP2, MTA1, TMEM121
Give two examples of single-gene disorders associated with chromosome 14.
1) FOXG1 syndrome (14q12) - all dn AD cases, LOF/deletions. Microcephaly, impaired development, severe brain abnormalities, severe ID. Associated with congenital Rett syndrome in males.
2) Alpha-1 antitrypisin deficiency (SERPINA1, AR, 14q32.13)
3) Leber congenital amaurosis/Cone-rod dystrophy (RPGRIP1, 14q11.2)
4) Hypertrophic cardiomyopathy (MYH7, 14q11.2)
