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Trisomy 22 (mosaic)
Also known as mosaic trisomy 22 · cat-eye syndrome is related (partial trisomy 22)
This condition arises from random errors during cell division after conception, resulting in a mix of cells with normal and abnormal chromosome counts. Clinical features vary widely depending on the proportion and distribution of affected cells, with most individuals experiencing developmental delays and physical differences.
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Overview
Mosaic trisomy 22 occurs when an individual has two distinct populations of cells: some with the typical 46 chromosomes and others with 47 chromosomes due to an extra copy of chromosome 22. The term 'mosaic' describes this mixture, where the additional chromosome is present in only a portion of the body's cells rather than all of them. This contrasts with complete trisomy 22, where every cell carries the extra chromosome. Complete trisomy 22 is almost universally incompatible with life beyond early pregnancy, with most affected pregnancies ending in miscarriage during the first trimester. Mosaic trisomy 22, however, permits survival because a sufficient proportion of cells retain the normal chromosome complement.
The proportion of cells carrying the extra chromosome can vary considerably between individuals and even between different tissues within the same person. This variability directly influences the severity and range of clinical features observed. Some individuals with a very low proportion of trisomic cells may have subtle features and near-normal development, whilst those with higher proportions typically experience more significant challenges. The condition is exceptionally rare, and precise prevalence figures are not well established due to the likelihood that mildly affected individuals may never receive a diagnosis.
Because the chromosomal abnormality occurs after fertilisation through random errors in cell division, mosaic trisomy 22 is not inherited from parents and does not run in families. Parents of an affected child have chromosomally normal cells themselves, and the recurrence risk for future pregnancies is not elevated above the background population risk.
Symptoms & clinical features
Clinical features of mosaic trisomy 22 are highly variable, reflecting differences in the proportion and distribution of trisomic cells across body systems. Developmental delay is commonly reported, with affected individuals often experiencing delays in reaching milestones such as sitting, walking, and speech development. Intellectual disability ranges from mild to moderate in most cases, though learning abilities vary considerably. Physical growth may be affected, with some individuals showing reduced growth rates and smaller stature compared to peers.
Physical features can include differences in facial appearance, though these are typically less distinctive than in many other chromosomal disorders. Some individuals have been reported to have widely spaced eyes, a smaller head circumference, low-set ears, or subtle asymmetry of facial features. Structural differences affecting internal organs may occur, including heart defects such as septal defects or valve abnormalities, kidney malformations, and gastrointestinal issues. Not all individuals experience these structural problems, and many have normal organ development.
Other reported features include hypotonia (reduced muscle tone) in infancy, which can affect feeding and motor development. Some affected individuals experience recurrent infections, possibly related to immune system differences. Skin pigmentation irregularities, where patches of skin appear lighter or darker than surrounding areas, have been observed in some cases and may reflect the mosaic distribution of cells. Behavioural and social development varies, with some individuals showing autistic features or attention difficulties, though these are not universal findings.
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Affected organs
The organs and body systems affected in mosaic trisomy 22 depend on which tissues harbour the chromosomal abnormality and in what proportion. The central nervous system is frequently affected, with brain development influenced by the presence of trisomic cells. This can manifest as structural brain differences detectable on imaging, though many individuals have structurally normal brains with functional impacts on cognition and development instead.
The cardiovascular system may be involved, with congenital heart defects reported in a proportion of cases. These can range from minor abnormalities requiring no intervention to more significant structural problems necessitating surgical correction. The urinary system, particularly the kidneys, can show developmental anomalies including absent or malformed kidneys, though this is not a consistent finding. The gastrointestinal tract may be affected, with reports of structural malformations or functional issues affecting feeding and digestion. Musculoskeletal features such as joint laxity or skeletal differences occur in some individuals but are generally not severe.
Risks & severity
The severity spectrum of mosaic trisomy 22 is exceptionally broad, ranging from individuals with very mild features who may never come to medical attention, to those with significant developmental challenges and multiple organ system involvement. The primary factor influencing severity is the percentage of cells carrying the extra chromosome and their distribution across critical tissues such as the brain and major organs. Individuals with lower levels of mosaicism, particularly if trisomic cells are largely absent from the brain, tend to have better developmental outcomes.
Lifetime health risks relate primarily to the specific organ systems affected. Individuals with congenital heart defects face risks associated with those structural abnormalities and may require cardiac monitoring and interventions. Those with kidney malformations may experience impaired renal function and associated complications. Developmental and intellectual challenges persist throughout life, though many individuals make continued progress with appropriate educational and therapeutic support. Life expectancy data are limited due to the rarity of the condition, but many individuals survive into adulthood, particularly those without major structural organ defects.
The sporadic nature of mosaic trisomy 22 means it arises through random events during early development rather than being passed down through families. Parents who have one child with mosaic trisomy 22 do not face an increased risk of having another affected child compared to the general population. Advanced maternal age does not appear to be a significant risk factor, unlike some other chromosomal disorders.
Genetic causes
Mosaic trisomy 22 results from an error in chromosome separation during cell division after fertilisation has occurred. Normally, cells contain 23 pairs of chromosomes, including two copies of chromosome 22. In mosaic trisomy 22, some cells acquire an additional copy of this chromosome, resulting in three copies instead of two within those cells. This chromosomal gain typically occurs during one of the early cell divisions following conception, creating a 'founding' trisomic cell that gives rise to a lineage of cells all carrying the extra chromosome.
Chromosome 22 contains hundreds of genes involved in diverse biological processes including brain development, immune function, and structural development of various organs. Having three copies of these genes instead of two disrupts the normal balance of gene expression, where cells expect precisely two copies of each gene to produce appropriate amounts of the encoded proteins. This dosage imbalance affects developmental pathways and cellular functions, though the specific mechanisms linking the chromosomal abnormality to particular clinical features remain incompletely understood.
The earlier in development the chromosomal error occurs, the higher the proportion of cells that will carry the abnormality, generally correlating with more significant clinical impact. Conversely, errors occurring later in development affect fewer cells and may result in milder presentations. The specific tissues and organs affected depend on which cell populations descended from the initial trisomic cell, explaining the marked variability in clinical features between individuals.
Inheritance pattern
Mosaic trisomy 22 is not inherited from parents and does not follow a predictable inheritance pattern. The condition arises through a spontaneous error in cell division after fertilisation, meaning it represents a new occurrence rather than a genetic change passed down through generations. Parents of a child with mosaic trisomy 22 have chromosomally normal cells themselves and did not contribute the chromosomal abnormality through their egg or sperm.
Because the chromosomal error occurs randomly during early development, the recurrence risk for parents who have had one affected child is not increased compared to the general population. Future children conceived by the same parents have the same very low background risk of chromosomal abnormalities that applies to all pregnancies. Affected individuals themselves could theoretically have children, and the risk to their offspring would depend on whether their reproductive cells (eggs or sperm) carry the chromosomal abnormality. Genetic counselling can help address questions about reproductive risks for affected individuals who reach adulthood.
Diagnosis & testing
Diagnosis of mosaic trisomy 22 is established through chromosomal analysis, most commonly via karyotyping, which examines chromosomes from dividing cells under a microscope. Because the condition involves a mixture of normal and abnormal cells, detecting mosaicism requires analysing a sufficient number of cells to identify both populations. Standard karyotyping typically examines 20-30 cells, but if mosaicism is suspected, a larger number may be counted to better characterise the proportion of trisomic cells.
Diagnosis may occur prenatally if chromosomal testing is performed during pregnancy for other indications, such as abnormal ultrasound findings or maternal serum screening results suggesting chromosomal abnormality. Chorionic villus sampling or amniocentesis can detect the condition, though the proportion of trisomic cells in prenatal samples may not perfectly reflect the proportion in the developing baby. Postnatal diagnosis typically follows recognition of developmental delays, physical features, or organ abnormalities that prompt chromosomal testing. Some individuals with very mild features may not be diagnosed until later in childhood or may never receive a diagnosis if clinical suspicion does not arise. Referral to NHS clinical genetics services is appropriate when mosaic trisomy 22 is suspected or confirmed, enabling access to specialist assessment, genetic counselling, and coordination of ongoing care.
Management & lifestyle
Management of mosaic trisomy 22 focuses on addressing the specific medical and developmental needs identified in each individual, as there is no treatment to alter the underlying chromosomal abnormality. Early developmental assessment and intervention are important, with referral to paediatric specialists including developmental paediatricians, speech and language therapists, physiotherapists, and occupational therapists based on identified needs. Educational support tailored to the individual's learning profile helps optimise developmental progress and skill acquisition.
Medical surveillance depends on the organ systems affected. Individuals with congenital heart defects require cardiology follow-up, with treatment ranging from monitoring to surgical intervention depending on severity. Kidney abnormalities necessitate nephrology input and monitoring of renal function. Growth and nutrition should be monitored, with dietetic support provided if feeding difficulties or growth faltering occur. Regular developmental and medical reviews allow early identification of emerging issues such as hearing or vision problems, which can be addressed promptly to support optimal development.
Families benefit from access to genetic counselling, which provides information about the condition, addresses questions about recurrence risks, and supports informed decision-making. Connection with support organisations and other families affected by rare chromosomal disorders can provide valuable peer support and shared experience. As affected individuals transition to adulthood, planning for ongoing support needs, including educational, vocational, and residential considerations, becomes important. Lifestyle considerations are generally individualised based on each person's abilities and medical needs rather than being dictated by the diagnosis itself.
UK care pathway
Within the NHS Genomic Medicine Service, mosaic trisomy 22 is managed through clinical genetics services rather than via a specific PanelApp R-code, as the diagnosis is established through chromosomal analysis rather than targeted gene panel testing. Referral to clinical genetics is appropriate following diagnosis or when the condition is suspected based on clinical features. The clinical genetics team provides specialist assessment, coordinates diagnostic testing if not already completed, and offers genetic counselling to families.
Access to genetic counsellors is a key component of the care pathway, supporting families in understanding the chromosomal basis of the condition, its sporadic nature, and implications for family planning. Multidisciplinary care involves coordination between clinical genetics, relevant paediatric subspecialties, developmental services, and educational providers to address the individual's specific needs. Transition planning for affected individuals moving from paediatric to adult services ensures continuity of care and appropriate ongoing support.
Frequently asked questions
Will my other children or future pregnancies be affected by trisomy 22?
No, mosaic trisomy 22 occurs through a random error in cell division after conception and is not inherited. Parents of an affected child have chromosomally normal cells and face no increased risk of having another child with the condition compared to the general population.
Can testing determine how severely my child will be affected?
The proportion of cells carrying the extra chromosome can provide some indication, with higher proportions generally associated with more significant features. However, predicting specific outcomes remains challenging because the distribution of affected cells across different tissues, particularly the brain, also influences development and cannot always be determined from blood testing alone.
Is there any treatment to correct the chromosomal abnormality?
There is currently no treatment that can change the chromosome count in cells. Management focuses on addressing specific medical needs such as heart defects or developmental delays through appropriate interventions, therapies, and educational support tailored to the individual.
Could mosaic trisomy 22 have been prevented?
No, the chromosomal error occurs randomly during early development and is not caused by anything parents did or did not do during pregnancy. It is not related to maternal age, environmental exposures, or lifestyle factors, and could not have been prevented.
Where can I find support and connect with other families?
Your clinical genetics team can direct you to relevant support organisations for families affected by rare chromosomal disorders. Genetic counsellors can also provide information about support networks and help connect you with resources appropriate to your family's needs.
References
- Firn K, Khazaeni L, Faherty E. Cat Eye Syndrome (Schmid-Fraccaro Syndrome). 2025. PMID: 40465813
- Trevisan V, Meroni A, Leoni C. Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature. Genes. 2024. PMID: 38540405
- Zhou L, Li H, Xu C. Characteristics and mechanisms of mosaicism in prenatal diagnosis cases by application of SNP array. Molecular cytogenetics. 2023. PMID: 37400883
- Ma L, Ouyang Y, Qi Q. Trisomy 22 with long spina bifida occulta: A case report. Medicine. 2018. PMID: 30278506
- Heinrich T, Nanda I, Rehn M. Live-born trisomy 22: patient report and review. Molecular syndromology. 2013. PMID: 23599696
- Chen CP, Huang MC, Chern SR. Mosaic trisomy 22 at amniocentesis: Prenatal diagnosis and literature review. Taiwanese journal of obstetrics & gynecology. 2019. PMID: 31542095
- Niikawa N, Merotto E, Kajii T. Origin of acrocentric trisomies in spontaneous abortuses. Human genetics. 1977. PMID: 604246
- Mokate T, Leask K, Mehta S. Non-mosaic trisomy 22: a report of 2 cases. Prenatal diagnosis. 2006. PMID: 16906599