How is jacobsen syndrome detected

It has four exons and encodes a homeobox protein. Its murine homologue barx2 is expressed in the development of neural and craniofacial structures [ 46 ]. However no mutation in the BARX2 gene has been detected in nine patients with isolated trigonocephaly [ 46 ].

JAM3 has been considered a candidate gene for hypoplastic left heart and trigonocephaly. It is a member of the junction adhesion molecules family; the gene maps within the critical region for hypoplastic left heart HLH that is a 9 Mb region in the long arm of chromosome 11 distal to D11S Analysis of the JAM3 gene in thirty-three patients with isolated HLH, failed to demonstrate any mutation; this would suggest that other genes are mainly involved in this malformation [ 7 ].

Tyson et al. B3GAT1 , a beta-1—3-glycoronyltransferase gene located in 11q25 at Knock out mice show impaired synaptic plasticity and learning disabilities [ 47 ]. This gene could be involved in bipolar disorder observed in some JS patients [ 12 ]. BSX , an evolutionarily highly conserved homeobox gene, expressed during early brain development and mapping in Abnormalities of the white matter appear to map between TECTA , a gene coding for a non collagenous component of the tectorial membrane of the inner ear, may be involved in neurosensorial deafness [ 48 ].

In patients with the classical phenotype the diagnosis is suspected on the basis of clinical findings: mental retardation, facial dysmorphic features and thrombocytopenia. The diagnosis must be confirmed by cytogenetic analysis. The clinical diagnosis may be difficult in patients with less characteristic clinical aspects and borderline mental development; in these cases the observation of thrombocytopenia or pancytopenia may suggest the diagnosis.

Children with fewer manifestations of JS may be less likely to be diagnosed early, based on clinical phenotype. Children with JS share some clinical features short stature, short, wide, sometimes webbed neck, downslanting palpebral fissures, ptosis, aortic or pulmonary stenosis with Turner and Noonan syndromes.

In Noonan syndrome patients, common features with JS patient are also thrombocytopenia and bleeding tendency.

Occasionally, JS children have had a clinical diagnosis of Kabuki syndrome mental retardation, unusual palpebral fissures, short stature, fingerpads. Neonatal bleeding and thrombocytopenia may be misdiagnosed as acquired thrombocytopenia due to sepsis. In families with a de novo chromosome rearrangement the recurrence risk is generally considered negligible. However in de novo terminal deletions 11q, recurrence has been documented in at least four children from two unrelated families [ 3 , 49 ].

Therefore prenatal diagnosis is warranted as the possibility of gonadal mosaicism or any other predisposing condition in one parent cannot be excluded. In families with the fragile site FRA11B , the recurrence risk is non quantifiable but probably slightly increased, and prenatal diagnosis could be considered.

There is a high recurrence risk when a parent has a balanced translocation, or deletion 11q in the mosaic form. Only a few prenatal cases of 11q terminal deletion have been reported [ 50 — 52 ]. 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.

The test is indicated when there is a known risk for 11q deletion familial balanced translocation, mosaicism or FRA11B in a parent.

The cytogenetic test may also be performed when there is an abnormal prenatal serum screening test for Down syndrome or abnormal prenatal ultrasound that may suggest the occurrence of a chromosome unbalance.

In some cases of deletion 11q, oligohydramnios, nuchal thickening, heart malformations and kidney duplication have been observed prenatally. In the neonatal period children with JS frequently require special assistance and treatment. JS children may have difficulties in feeding and tube feeding may be necessary.

Due to thrombocytopenia and abnormal platelet function, bleeding is most likely to occur in infancy. Platelet count can eventually reach low normal values, but functional abnormalities usually persist. In some patients pancytopenia is observed. Prophylactic platelets or whole blood transfusion may be necessary before, as well as during or after surgery. Bone marrow biopsy is usually not necessary. Early craniotomy is indicated in children with craniosynostosis.

During the first years of life children have an increased risk of recurrent infections. Thyroid hormone deficiency should be treated accordingly. Treatment with growth hormone replacement therapy is controversial, since these patients may have a genetic predisposition to certain malignancies that could be exacerbated by a tumor promoter. Eye surgery may be necessary to correct strabismus, as untreated strabismus may result in amblyopia.

It is critical that surgery be performed in the first year of life to prevent this complication. Severe ptosis must be corrected to allow walking; however abnormal external eye muscles may cause relapse of ptosis or strabismus after surgery.

Treatment of orthopedic problems should be individualized. Early intervention with occupation, speech, physical and behavioral therapists is critical to address cognitive and behavioral problems.

Recently, music therapy has been shown to be beneficial to some of these patients manuscript in preparation. JS children can be vaccinated according to the standard schedule [ 3 ].

As described above, children with JS frequently require surgical treatment interventions. Thrombocytopenia and other hematological problems must be taken into account preoperatively. Prophylactic transfusion with platelets can be lifesaving. Due to abnormalities of the pharynx maintaining the airway and intubation might be difficult [ 53 ]. A proportion of children with JS die in the neonatal period, usually due to severe heart malformations and bleeding.

Many patients that survive the neonatal period will require long-term care including surgical and medical interventions. Life expectancy is unknown. The oldest known living patient with JS is 45 years old. There is apparently no known increased risk of malignancies. Written consent for publication of photographs was obtained from the patients or legal guardians where required.

A clinical, cytogenetical, and gene marker study. Hum Hered. Am J Hum Genet. Am J Med Genet. Article PubMed Google Scholar. J Med Genet. Am J Med Genetic. Am J Med Genet A. Mol Cytogenet. Google Scholar. Genet Couns. Clin Genet. Thromb Haemost. Am J Med Haematol. White JG: Platelet storage pool deficiency in Jacobsen syndrome.

Article Google Scholar. Arch Pediatr. J Pathol. A case report and review of the literature. Ann Genet. Eur J Pediatr. Hum Gene. Hum Mol Genet. Upturned nose. Upturned nostrils.

Absence of eyebrow. Lack of eyebrow. Missing eyebrow. Attention deficit. Attention deficit disorder. Attention deficit-hyperactivity disorder. Attention deficits. Broad bone of big toe. Wide bone of big toe. Undescended testes. Undescended testis. Downward slanting of the opening between the eyelids.

Eye folds. Prominent eye folds. Asymmetry of face. Crooked face. Unsymmetrical face. Wide-set eyes. Widely spaced eyes. Long big toe. Increased size of skull. Large head. Large head circumference. Cornea of eye less than 10mm in diameter. Absent ribs. Decreased rib number. Flat feet. Flat foot. Premature delivery of affected infants.

Preterm delivery. Drooping upper eyelid. Frequent respiratory infections. Multiple respiratory infections. Susceptibility to respiratory infections. Decreased length of neck. Decreased length of nose. Shortened nose. Decreased body height. Small stature. Short toes. Stubby toes. Squint eyes. Fused toes. Webbed toes. Hole in heart wall separating two lower heart chambers.

Abnormality of the palate. Abnormality of the roof of the mouth. Narrowing of aortic valve. Bipolar disorder. Clouding of the lens of the eye.

Cloudy lens. Degeneration of cerebrum. Narrowing of aorta. Narrowing of the aorta. Infantile death. Lethal in infancy. Absence or narrowing of first part of small bowel. Abnormal anus position. Eyelid turned out. Cleft eyelid. Notched eyelid. Extra finger. Dislocated hips. Dislocation of hip. Underdeveloped left heart. Prenatal growth deficiency. Prenatal growth retardation. Cat eye. Fewer and broader ridges in brain. Triangular skull shape. Wedge shaped skull.

Neck webbing. Broad nasal bridge. Broad nasal root. Broadened nasal bridge. Increased breadth of bridge of nose. Increased breadth of nasal bridge. Increased width of bridge of nose. Increased width of nasal bridge. Nasal bridge broad. Wide bridge of nose. Widened nasal bridge. Abnormal eyelashes. Abnormality of the eyelashes. Eyelash abnormality. Lazy eye. Wandering eye. An opening in the wall separating the top two chambers of the heart. Hole in heart wall separating two upper heart chambers.

Short fingers or toes. Birth defect that causes a hole in the innermost layer at the back of the eye. Permanent curving of the pinkie finger.

Small clitoris. Underdeveloped clit. Depressed bridge of nose. Flat bridge of nose. Flat nasal bridge. Flat, nasal bridge. Early diagnosis of the syndrome can lead to lifesaving interventions including the need for prophylactic platelet transfusions at times of risk to prevent bleeding, prophylactic antibiotic or IVIG infusions to prevent life-threatening infections, early medical or surgical intervention for complex congenital heart defects, and brain imaging to identify potential life-threatening brain aneurysms.

Intellectual disability can range from mild to severe. For patients who survive the neonatal period and infancy, the life expectancy remains unknown. Other search option s Alphabetical list. Suggest an update. Summary and related texts. Related genes.

Clinical signs. To get in touch with the Orphanet team, please contact Information provided in your contribution including your email address will be stocked in. Check this box if you wish to receive a copy of your message. Disease definition A rare genetic disorder caused by deletions in the long arm of chromosome 11 11q and mainly characterized by craniofacial dysmorphism, congenital heart disease, intellectual disability, Paris Trousseau bleeding disorder, structural kidney defects and immunodeficiency.

Clinical description Jacobsen syndrome is contiguous gene disorder, characterized by craniofacial dysmorphism skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, a broad nasal bridge, short nose, V-shaped mouth, and small, low-set and posteriorly rotated ears , craniosynostosis, eye abnormalities, congenital heart disease, intellectual disability, behavioral problems including ADHD and autism, seizures, Paris-Trousseau bleeding disorder, structural kidney defects and other urogenital anomalies including undescended testes in males, chronic constipation, pyloric stenosis, and immunodeficiency.

Etiology The syndrome is caused by deletion of one copy of the long arm of chromosome 11 11q. Differential diagnosis Differential diagnoses may include the Turner and Noonan syndromes, as well as acquired thrombocytopenia due to sepsis. Antenatal diagnosis Prenatal diagnosis of 11q deletion is possible through array comparative genomic hybridization analysis of genomic DNA from amniocytes or chorionic villus samples.