Jacobsen syndrome
Jacobsen syndrome is a chromosomal aberration ( = chromosomal disorder ) in which a deletion has occurred in the q arm of chromosome 11. This deletion is usually terminal, that is, it comprises the telomere. The size of the deletion is not always the same, but varies among those affected. The syndrome is extremely rare and has been described by the Danish physician Petra Jacobsen first.
Symptoms
The symptoms of Jacobsen syndrome are very different and variable pronounced. A characteristic phenotype is noted however.
Characteristic phenotype
- Trigonocephaly ( Triangular head)
- Hypertelorism ( widely spaced eyes)
- Decreased growth
- Developmental delays
- Non - horizontal eyelid
- Strabismus ( squint)
- Epicanthus medialis ( Mongolian fold )
- Falling lower lip
- Mandibular retrognathia ( Withdrawn pine)
- Cleft palate
- Short neck
- Deep -employed and dysplastic ears
- Widely spaced nipples
- Hand furrows
Not only the externals is altered in affected individuals, but they often also suffer from organ malformations and functional disorders.
Organs
The most common symptom of disease occurs in 94 % of those affected. It involves the Paris - Trousseau syndrome, a congenital reduction in platelet production, leading to increased bleeding.
56% of affected suffer from a congenital malformation of the heart. This is 2/3 of the cases the absence or hypoplasia of the left ventricle.
Neuronal and cognitive
Most children suffer from mild (IQ <80 ) or medium (IQ <50) mental retardation ( disability). Rarely is a normal mental development to be found.
The patients have a normal uptake, however, have mild to moderate disturbances in their expressiveness, ie the ability to express themselves. A disorder of fine and gross motor skills are also common.
The optical system
11% of patients suffering from an iris coloboma. This is a defect of the iris, which is caused by a defective eye cup closure. In addition, frequently occurs cataract ( cataract ) and a dysplastic retina.
Molecular Aspects
The deletion in the q arm of chromosome 11 is caused by a break in the chromosome. The most common fracture location is the location 11q23.3, which is also called FRA11B. At this point of the chromosome is found in front of a series of repeats of the nucleotide triplets " CCG " which is also referred to as the CCG repeats.
When Jacobsen syndrome results in expansion and Hypermethylisierung the CCG repeats. Thus, the folate- sensitive fragile site in FRA11B is expressed, which probably leads to breakage.
There have been discovered another 6 break points below the FRA11B. All contain CCG repeats, but no further folic acid sensitive fragile site. These deletions are exclusively inherited from the father. This suggests that paternal imprinting. Why this is the case and why there can be a fraction of the chromosome here, however, is unclear.
Forecast
About one-fifth of affected infants die within the first two years of life. The most common cause of death is a congenital heart defect, occasionally, the bleeding. Through a heart surgery, speech therapy, platelet transfusions and regular check-ups, however, the life expectancy and quality of life can be improved slightly. For life expectancy, the first two years of surviving patients no details have so far been published.