21q deletion syndrome (ORPHA:574)
Monosomy 21 is a chromosomal anomaly characterized by the loss of variable portions of a segment of the long arm of chromosome 21 that leads to an increased risk of birth defects, developmental delay and intellectual deficit.
Epidemiology
Monosomy 21 is a very rare condition with less than 50 cases described in the literature. Full monosomy 21 is probably not compatible with life.
Clinical description
The severity of the phenotype depends on the location and size of the deleted area. In general, proximal and distal deletions lead to a milder phenotype (e.g. few dysmorphic features or congenital anomalies, and mild to moderate intellectual deficit), whereas deletions involving band 21q22 have a more severe effect on the phenotype. In the later case, the most common clinical features include intrauterine and postnatal growth retardation, microcephaly, prominent occiput, and facial dysmorphism characterized by up or down-slanted small palpebral fissures, prominent nasal bridge with a broad nose, and large ears. Multiple malformations including structural brain malformations (e.g. cerebral atrophy, cortical dysplasia, and corpus callosum dysgenesis) and heart defects (e.g. patent ductus arteriosus, septal defects) are also frequently observed. Severe intellectual deficit is common. Joints may be stiff and held in an unusual position. Abnormal muscle tone, respiratory infections and seizures are usual. Specific blood disorders (e.g. thrombocytopenia, myelodysplasia) have been reported.
Etiology
The disease is due to the loss of variable portions of the long arm of chromosome 21. Partial 21q deletions are interstitial or terminal. They occur de novo or as the result of a parental rearrangement. Monosomy due to malsegregation of a parental rearrangement is usually associated with another imbalance that could complicate the phenotype. Some cases result from formation of a ring chromosome 21.
Diagnostic methods
Diagnosis is based on clinical findings that lead to chromosomal analysis. Depending on their size, partial 21q deletions may be diagnosed by classical or molecular karyotyping. Molecular techniques are necessary for the genetic characterization of the deletion.
Antenatal diagnosis
Prenatal diagnosis of 21q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis.
Genetic counseling
The risk of having another affected child is higher if a chromosomal rearrangement is present in one of the parents.
Management and treatment
Management is multi-disciplinary and requires evaluation and treatment by a general pediatrician, and relevant specialists. Children will benefit from early assessment and access to the major developmental therapies. Physiotherapy may be important to improve both the muscle tone and the joints flexibility.
Prognosis
Prognosis depends on the size and location of the deletion. It is severe if band 21q22 is involved, with vital prognosis depending on the severity of congenital malformations.

                            Last update: 
                            January 2012


                            - Expert reviewer(s): 
                            Dr Catherine TURLEAU