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Kagami-Ogata syndrome
Kagami-Ogata syndrome is a rare genetic condition characterised by distinctive facial features, intellectual disability, and developmental delays. It results from a problem with genetic imprinting on chromosome 14 and affects individuals from birth.
Overview
Kagami-Ogata syndrome, also known as upd(14)pat or paternal uniparental disomy of chromosome 14, is a rare genetic disorder. It is characterised by a unique set of physical features, developmental delays, and intellectual disability [PMID:33677494]. This condition arises from an issue with how certain genes on chromosome 14 are 'imprinted' - a process where genes are expressed differently depending on whether they are inherited from the mother or the father. In Kagami-Ogata syndrome, there is an imbalance in this imprinting, typically involving too many paternally expressed genes from chromosome 14. This imbalance disrupts normal development, leading to the features associated with the syndrome [PMID:24075114].
Symptoms & clinical features
Individuals with Kagami-Ogata syndrome often present with a range of symptoms, which can vary in severity. Common features include distinctive facial characteristics, such as a prominent philtrum (the groove between the base of the nose and the upper lip) and a small mouth. Feeding difficulties are frequently observed in infancy, alongside respiratory issues that may sometimes require medical intervention [PMID:24075114].
Developmental delays are a significant aspect of the syndrome, affecting motor skills, speech, and overall cognitive development. Most individuals experience some degree of intellectual disability. Skeletal abnormalities, such as a narrow chest or curved bones, may also be present. In some cases, there can be complications like scoliosis (curvature of the spine) or joint contractures, which limit movement. Sleep apnoea is also commonly reported.
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Affected organs
Kagami-Ogata syndrome primarily affects several body systems, reflecting the wide-ranging impact of the genetic imbalance. The central nervous system is affected, leading to developmental delays and intellectual disability. The craniofacial region shows characteristic features, influencing the structure of the face. The respiratory system can be impacted, leading to breathing difficulties, particularly in infancy. Skeletal development is also commonly affected, with potential for abnormalities in bone structure and joint movement. Additionally, feeding and gastrointestinal functions can be challenging for affected individuals.
Risks & severity
The severity of Kagami-Ogata syndrome can vary among affected individuals, although most experience significant developmental challenges. The condition is present from birth, and symptoms are usually noticeable early in life. Respiratory and feeding difficulties in infancy can be severe, sometimes requiring intensive medical support. The degree of intellectual disability also varies, but most individuals will require ongoing support throughout their lives.
Since this is a genetic condition present from conception, the lifetime risks are inherent to the diagnosis. There are no specific environmental risk factors that cause the syndrome to develop once the genetic change has occurred. The exact prevalence of Kagami-Ogata syndrome is not well established due to its rarity, but it is considered a very rare disorder.
Genetic causes
Kagami-Ogata syndrome is a genetic condition primarily caused by an alteration in the imprinting of genes on chromosome 14, specifically in the 14q32 region. Genetic imprinting is a process where only one copy of a gene (either from the mother or the father) is active, while the other is silenced. For some genes, only the copy from the mother is active; for others, only the copy from the father is active.
In Kagami-Ogata syndrome, the main cause is usually paternal uniparental disomy of chromosome 14 (upd(14)pat), meaning an individual has inherited both copies of chromosome 14 from their father, and none from their mother [PMID:33677494]. This leads to an over-expression of paternally expressed genes and a complete absence of maternally expressed genes in this critical region. Other causes can include duplications of the paternal 14q32 region or specific imprinting defects within this area, all resulting in the same functional imbalance of gene expression.
Inheritance pattern
Kagami-Ogata syndrome follows an imprinted inheritance pattern. This means the way the condition is inherited depends on which parent the altered genetic material comes from. In the typical form of Kagami-Ogata syndrome, where both copies of chromosome 14 come from the father (paternal uniparental disomy), the condition is usually not inherited from a parent in a straightforward dominant or recessive manner.
If the cause is paternal uniparental disomy, the parents of an affected child are typically not affected themselves and the chance of having another child with the syndrome is generally low, although genetic counselling is recommended to assess specific family risks. If the cause is a duplication or a specific imprinting defect that one parent carries, there might be a recurrence risk. Genetic counselling is crucial to understand the specific genetic mechanism in each family and to provide accurate information on recurrence risks for future pregnancies.
Diagnosis & testing
Diagnosis of Kagami-Ogata syndrome is typically suspected based on characteristic clinical features observed during infancy or early childhood. These include the distinctive facial appearance, developmental delays, and feeding or respiratory difficulties. Once clinical suspicion is raised, genetic testing is used to confirm the diagnosis.
Genetic testing focuses on chromosome 14, specifically looking for abnormalities in the 14q32 region. This may involve tests such as methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) or chromosomal microarray analysis, which can detect uniparental disomy or specific imprinting defects. Referral to clinical genetics services in the NHS would be appropriate for suspected cases. The NHS Genomic Medicine Service offers genomic testing, and an R-code, such as R222 (Intellectual disability - syndromic), may be applicable for testing when there are specific clinical indicators.
Management & lifestyle
Management for individuals with Kagami-Ogata syndrome is supportive and multidisciplinary, addressing the specific symptoms and challenges experienced. This typically involves a team of specialists including paediatricians, neurologists, geneticists, speech and language therapists, physiotherapists, and occupational therapists. Early intervention programmes are crucial to support developmental progress.
Regular monitoring for potential complications such as respiratory issues, feeding difficulties, and skeletal problems is important. Respiratory support, such as supplemental oxygen or non-invasive ventilation, may be needed in some cases. Feeding interventions, including specialised diets or feeding tubes, might be necessary for infants with severe difficulties. Ongoing therapy helps individuals achieve their developmental potential and improve their quality of life. Access to these services is typically coordinated through paediatric and community health services within the NHS, often following an initial assessment by a clinical geneticist.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like Kagami-Ogata syndrome would typically be referred by their GP or paediatrician to a clinical genetics service. These services are part of the NHS Genomic Medicine Service (GMS). A clinical geneticist would assess the individual and family history, and if Kagami-Ogata syndrome is suspected, they would arrange for appropriate genomic testing. Genetic counsellors within these services provide essential support and information to families, explaining the condition, its inheritance, and implications for family members. Relevant NHS R-codes are used to guide the diagnostic testing pathway for rare diseases with intellectual disability.
Frequently asked questions
What is genetic imprinting?
Genetic imprinting is a normal process where only one copy of a gene is active, depending on whether it came from the mother or the father. The other copy is 'silenced'. In conditions like Kagami-Ogata syndrome, this normal imprinting process is disrupted.
Is Kagami-Ogata syndrome hereditary?
In most cases of Kagami-Ogata syndrome caused by paternal uniparental disomy, it is not inherited from a parent in the typical sense. However, if the cause is a specific imprinting defect or a duplication, there might be a recurrence risk. Genetic counselling can provide clarity on individual family circumstances.
What support is available for families affected by Kagami-Ogata syndrome?
Families can access a range of support services through the NHS, including specialist paediatric care, genetic counselling, and various therapies like speech, physical, and occupational therapy. Support groups and rare disease organisations can also offer valuable resources and community connection.
Are there specific treatments for Kagami-Ogata syndrome?
There is no specific cure for Kagami-Ogata syndrome. Management focuses on treating the symptoms and providing supportive care. This includes therapies to aid development, interventions for feeding and respiratory issues, and ongoing medical monitoring.
How rare is Kagami-Ogata syndrome?
Kagami-Ogata syndrome is considered a very rare condition. The exact prevalence is not precisely known, but it is one of several very rare genetic disorders caused by imprinting defects.
References
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- Prasasya R, Grotheer KV, Siracusa LD. Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms. Human molecular genetics. 2020. PMID: 32592473
- Ogata T, Kagami M. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region. Journal of human genetics. 2016. PMID: 26377239
- Luk HM. Familial Kagami-Ogata syndrome in Chinese. Clinical dysmorphology. 2017. PMID: 27753651
- Suriapperuma T, Randeny S, Mettananda S. Kagami-Ogata syndrome: a case report. Journal of medical case reports. 2022. PMID: 35864517
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- Sakaria RP, Mostafavi R, Miller S. Kagami-Ogata Syndrome: Case Series and Review of Literature. AJP reports. 2021. PMID: 34055463
- Huang H, Mikami Y, Shigematsu K. Kagami-Ogata syndrome in a fetus presenting with polyhydramnios, malformations, and preterm delivery: a case report. Journal of medical case reports. 2019. PMID: 31753000