JACOBSEN'S SYNDROME

Alternate Names:  11q deletion disorder, Partial deletion 11q, Distal deletion 11q, Distal monosomy 11q, Telomeric deletion 11q, 11q-syndrome, Del 11q ter, Del 11q23.3

Children with Jacobsen's Syndrome

Overview: Jacobsen’s syndrome is caused by the loss genetic material from the terminus of the long (q) arm of chromosome 11.

Characteristic/Phenotype: The symptoms of Jacobsen’s syndrome vary considerably according to the extent of deletion. The most common characteristics would be delayed development of motor skills, along with learning and cognitive difficulties. Behavioral problems, such as compulsive behaviour, short attention span, easy distractability and ADHD have also been reported.

Facial anomalies which were identified were:

•    Small and low-set ears
•    Hypertelorism (widely set eyes)
•    Ptosis (droopy eyelids)
•    Epicanthal folds (skin folds on inner corners of the eyes)
•    Broad nasal bridge
•    Downturned corners of the mouth
•    Thin upper lip
•    Small lower jaw
•    Macrocephaly (large head)
•    Trigonocephaly (pointed forehead)

Also, approximately more than 90% of the people with the syndrome are also afflicted with Paris-Trouusseau syndrome, a bleeding disorder which causes a lifelong risk of abnormal bleeding and easy bruising. This is due to abnormal platelet structure.

Other associated features include heart defects, feeding difficulties after birth, short stature, frequent ear and sinus infections, and skeletal abnormalities. The digestive system, kidneys, and genitalia are also affected.

Frequency: The estimated incidence of Jacobsen syndrome is 1 in 100,000 newborns with a female/male ratio 2:1.

Diagnosis: In patients with the classical phenotype the diagnosis is suspected on the basis of clinical findings: mental retardation, facial dysmorphic features and thrombocytopenia. Cytogenetic analysis must confirm the syndrome, especially with larger deletions. Auditory tests, blood tests, endocrine and immunological assessment and follow-up should be offered to all patients.

Prenatal diagnosis of 11q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis with standard G-banding and, if necessary, telomeric FISH. Fluorescence in situ hybridization (FISH)-metaphase can detect the deletions using genetic markers via the absence of fluorescent signal from either the maternal or paternal chromosome 11q regions.

In some cases of deletion 11q, oligohydramnios (deficiency of amniotic fluid), nuchal thickening, heart malformations and kidney duplication have been observed prenatally.

Causes:  Eighty-five (85%)  of the cases are usually caused by a random spontaneous chromosomal deletion during the formation of reproductive cells or during early fetal development.

In some cases, a parent who carries a chromosomal rearrangement called a balanced translocation cause 5 to 15 % of cases even though the parent is unaffected as caused by the eventual imbalance (missing genetic material) as the chromosome is passed on to the next generation.

Families with de novo chromosomal rearrangement have negligible recurrence. Gonadal mosaicism can be possible, and in families with fragile site FRA11B, the recurrence is slightly increased. When a parent has the syndrome, the recurrence is 50% as well as if a parent has a balanced translocation.

Other data: The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood. The oldest known living patient with Jacobsen’s Syndrome is 45 years old. About 20% of children die during the first two years of life, most commonly related to complications from congenital heart disease, and less commonly from bleeding.

Mosaic forms have also been reported.

Treatment/Recommendations/Therapies: Heart malformations are common and usually severe so surgery may be required in the neonatal period. Difficulties in feeding are evident among children requiring tube feeding. Prophylactic platelets or whole blood transfusion may be required due to abnormal platelets. Infections are common so it is necessary to stabilize the infant’s immune system. Retarded growth may be augmented by growth hormone therapy although it can cause malignancies. Corrective surgery can be employed to minor malformations (strabismus, etc.).

Early intervention with occupation, speech, physical and behavioral therapists is critical to address cognitive and behavioral problems. It has been proven that music therapy has been shown to be beneficial to some patients. Patients can be vaccinated according to the standard schedule.

Genetic counselling is needed to inform parents of the condition and to approximate recurrence risks in families based on possible structural rearrangements of chromosome 11 of either parents. Female patients are usually fertile (with 50 % recurrence risk) may also require counselling.

Cognitive difficulties may be addressed with properly tailored learning programs to suit the patient’s development. Behavioral problems can be addressed by behaviour modification programs.  Patients usually respond well to structured environments.

Most children - often with the help of specific orthopedic interventions - overcome their poor muscle tone. With therapies, most children learn to write, use a computer, and feed and dress themselves. Aletrnative means of communication may be employed for language difficulties.

Support Groups:

Band Back Together

http://www.bandbacktogether.com/jacobsen-syndrome-resources/

References:

Genetics Home reference. (2009). Jacobsen Syndrome. Retrieved March 12, 2013 from the URL: http://ghr.nlm.nih.gov/condition/jacobsen-syndrome

Mattina, T. Et al. (2009). Jacobsen syndrome review. Retrieved March 12, 2013 from the URLs: http://www.ojrd.com/content/4/1/9 and http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2308

Photo from:
http://www.ojrd.com/content/figures/1750-1172-4-9-1-l.jpg