Genetics
Micro-deletion syndromes
Di- George syndrome
Aetiology
Deletion of part of the long arm in chromosome 22 at location 22q11.2(1)
The most common deletion includes the TBX1 gene (85% individuals), see figure 1 below.
Defect in neural-crest tissue (thyroid, thymus, and conotruncal septum of the heart) due deletion of region in chromosome 22 (2)
Inheritance pattern is autosomal dominant (2)
Hypoplasia of thymus and parathyroid glands resulting in hypocalcemia
Acronym CATCH22 is used for this syndrome (Cardiac Abnormality/abnormal facies, T cell deficit due to thymic hypoplasia, Cleft palate, Hypocalcemia ) (2) a variation in the phenotype and deletion can be in both maternal or paternal origin (1)
Figure 1: shows the genetic map of chromosomal region 22q11.2, 85% individuals have a large 3-Mb deletion (40 genes) (3).
Clinical features (1)
Cardiac malformations (aortic arch anomalies)
Dysmorphic facial features (low set ears , upward and downward slanting eyes, small mouth) (2)
Recurrent infections
Neonatal hypocalcaemia – tetany /Seizures
Investigations (3)
Chest Radiography – thymus
FISH (fluorescent in situ hybridisation) the probes TUPLE1 and N25 are used for breakpoints in the region
Incidence (4)
1 in 4000 of population (international)
References
1) Connor, J. and Ferguson-Smith, M. (1997). Essential medical genetics. 1st ed. Oxford [England]: Blackwell Science.
2) Omim.org, (2014). OMIM Entry - # 188400 - DIGEORGE SYNDROME; DGS. [online] Available at: http://www.omim.org/entry/188400?search=DI-GEORGE&highlight=digeorge [Accessed 2 Jun. 2014].
3) Roberta A Pagon, E. (2014). 22q11.2 Deletion Syndrome - GeneReviews® - NCBI Bookshelf. [online] Ncbi.nlm.nih.gov. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1523/ [Accessed 2 Jun. 2014].
4) Emedicine.medscape.com, (2014). Medscape: Medscape Access. [online] Available at: http://emedicine.medscape.com/article/886526-overview#a0156 [Accessed 2 Jun. 2014].
Prader Willi
Di- George syndrome
Aetiology
Deletion of part of the long arm in chromosome 22 at location 22q11.2(1)
The most common deletion includes the TBX1 gene (85% individuals), see figure 1 below.
Defect in neural-crest tissue (thyroid, thymus, and conotruncal septum of the heart) due deletion of region in chromosome 22 (2)
Inheritance pattern is autosomal dominant (2)
Hypoplasia of thymus and parathyroid glands resulting in hypocalcemia
Acronym CATCH22 is used for this syndrome (Cardiac Abnormality/abnormal facies, T cell deficit due to thymic hypoplasia, Cleft palate, Hypocalcemia ) (2) a variation in the phenotype and deletion can be in both maternal or paternal origin (1)
Figure 1: shows the genetic map of chromosomal region 22q11.2, 85% individuals have a large 3-Mb deletion (40 genes) (3).
Clinical features (1)
Cardiac malformations (aortic arch anomalies)
Dysmorphic facial features (low set ears , upward and downward slanting eyes, small mouth) (2)
Recurrent infections
Neonatal hypocalcaemia – tetany /Seizures
Investigations (3)
Chest Radiography – thymus
FISH (fluorescent in situ hybridisation) the probes TUPLE1 and N25 are used for breakpoints in the region
Incidence (4)
1 in 4000 of population (international)
References
1) Connor, J. and Ferguson-Smith, M. (1997). Essential medical genetics. 1st ed. Oxford [England]: Blackwell Science.
2) Omim.org, (2014). OMIM Entry - # 188400 - DIGEORGE SYNDROME; DGS. [online] Available at: http://www.omim.org/entry/188400?search=DI-GEORGE&highlight=digeorge [Accessed 2 Jun. 2014].
3) Roberta A Pagon, E. (2014). 22q11.2 Deletion Syndrome - GeneReviews® - NCBI Bookshelf. [online] Ncbi.nlm.nih.gov. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1523/ [Accessed 2 Jun. 2014].
4) Emedicine.medscape.com, (2014). Medscape: Medscape Access. [online] Available at: http://emedicine.medscape.com/article/886526-overview#a0156 [Accessed 2 Jun. 2014].
Prader Willi
References: 1) Roberta A Pagon, B. (2014). Retinoblastoma - GeneReviews® - NCBI Bookshelf. [online] Ncbi.nlm.nih.gov. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1452/ [Accessed 2 Jun. 2014]. 2) Omim.org, (2014). OMIM Entry - # 613884 - CHROMOSOME 13q14 DELETION SYNDROME. [online] Available at: http://www.omim.org/entry/613884 [Accessed 2 Jun. 2014].