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1p36 deletion syndrome
Also known as Monosomy 1p36 · 1p36 del
This rare genetic condition is typically characterised by intellectual disability, developmental delay, and distinctive facial features. It affects approximately 1 in 5,000 to 10,000 live births and usually occurs by chance.
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Overview
1p36 deletion syndrome is a genetic condition caused by the absence of a small piece of chromosome 1. Specifically, it involves the furthest part of the short arm (p arm) of chromosome 1, known as the 1p36 region. This region contains many genes that are important for normal development [PMID:20301749]. Because a segment of genetic material is missing, individuals with this syndrome often experience a range of health and developmental challenges. The severity and specific features can vary widely among affected individuals, depending on the exact size and location of the deleted segment.
Symptoms & clinical features
Individuals with 1p36 deletion syndrome often present with a combination of clinical features. Developmental delay is a common characteristic, impacting motor skills, speech, and cognitive abilities. Intellectual disability is also frequently observed, ranging from mild to severe [PMID:20301749].
Many individuals have distinctive facial features, which may include deep-set eyes, a broad nasal bridge, a pointed chin, and low-set, unusually shaped ears. Other common symptoms can include seizures, typically occurring in infancy or early childhood, and heart defects, which can vary in severity. Vision and hearing impairments are also reported in some individuals. Muscle weakness (hypotonia) and difficulties with feeding are commonly seen in infancy. Behavioural differences, such as attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) traits, may also be present.
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Affected organs
1p36 deletion syndrome can affect multiple organ systems due to the large number of genes involved in the deleted region. The brain is significantly impacted, leading to developmental delay, intellectual disability, and an increased risk of seizures. The heart is also frequently affected, with various congenital heart defects reported. Musculoskeletal issues, such as low muscle tone and skeletal anomalies, are common.
Risks & severity
The severity spectrum of 1p36 deletion syndrome is broad, with individuals experiencing different combinations and degrees of symptoms. The size and specific genes missing within the 1p36 region can influence symptom presentation. Most cases are de novo, meaning the deletion occurs spontaneously and is not inherited from a parent [PMID:20301749].
There is no specific lifetime risk percentage, as the condition is generally not inherited. The age of onset for developmental delays is typically in infancy, becoming more apparent as a child grows and misses developmental milestones. The prognosis varies, but many individuals will require lifelong support for their developmental and medical needs. The risk of recurrence in future children of unaffected parents is very low, as the deletion typically arises as a new genetic change.
Genetic causes
1p36 deletion syndrome is caused by a deletion, or missing segment, on the short arm of chromosome 1, specifically within the 1p36 band. Chromosomes contain our genetic material, and the 1p36 region holds many important genes. When this segment is missing, the body either produces too little of the proteins encoded by these genes or none at all, leading to the various symptoms of the syndrome. This type of genetic change is classified as a 'microdeletion' because it involves a small portion of a chromosome that might not be visible under a standard microscope.
While many genes contribute to the overall picture of 1p36 deletion syndrome, the SKI proto-oncogene (SKI) is one gene located in this critical region. SKI is involved in regulating cell growth and development through the TGF-beta pathway, a signalling pathway important for many cellular processes. The absence of one copy of the SKI gene, along with other genes in the deleted region, is thought to contribute to some of the developmental and clinical features observed in individuals with 1p36 deletion syndrome [PMID:33671754]. The exact contribution of each specific gene within the deleted region to the overall phenotype is still an active area of research.
- SKI SKI proto-oncogeneThe SKI gene provides instructions for making a protein that regulates cellular growth, division, and differentiation, primarily by modulating the transforming growth factor beta (TGF-β) signalling pathway.
Inheritance pattern
1p36 deletion syndrome is typically inherited in a chromosomal pattern. This means the condition results from a change in the structure of a chromosome. In most cases (around 95%), the deletion is 'de novo,' meaning it occurs spontaneously during the formation of reproductive cells (eggs or sperm) or in early embryonic development. This implies that the deletion is not present in either parent's genetic material and is a new event in the child [PMID:20301749].
In a smaller percentage of cases (about 5%), the deletion can be inherited from a parent who carries a 'balanced translocation'. In a balanced translocation, a piece of chromosome has broken off and reattached to another chromosome, but no genetic material is lost or gained. The parent is usually healthy because they have a complete set of genetic instructions. However, when passing on their chromosomes, they can pass on an unbalanced set, leading to a deletion or duplication in their child. Genetic counselling is recommended for families to understand recurrence risks.
Diagnosis & testing
Diagnosis of 1p36 deletion syndrome often begins with a clinical suspicion based on the presence of characteristic features such as developmental delay, intellectual disability, and distinctive facial features. If a doctor suspects a chromosomal abnormality, genetic testing will be recommended to confirm the diagnosis.
The primary method for confirming 1p36 deletion syndrome is genetic testing, typically using techniques such as chromosomal microarray (CMA) or fluorescence in situ hybridisation (FISH). CMA can detect small missing or extra pieces of chromosomes, including the 1p36 deletion [PMID:27878204]. FISH uses fluorescent probes to highlight specific regions on chromosomes. In the UK, genetic testing for suspected genomic disorders falls under the NHS Genomic Medicine Service (GMS) framework, and referrals for testing are usually made by a paediatrician or clinical geneticist according to specific R-codes.
Management & lifestyle
Management of 1p36 deletion syndrome is multidisciplinary and focuses on addressing the individual's specific symptoms and needs. There is no cure for the condition, so care aims to maximise developmental potential and manage associated medical issues. Early intervention is crucial and often includes various therapies such as physiotherapy, occupational therapy, and speech and language therapy to support developmental milestones.
Regular medical surveillance is important, especially for potential heart defects, seizures, and vision/hearing impairments. This may involve evaluations by a cardiologist, neurologist, ophthalmologist, or audiologist. Families are typically supported through the NHS care pathway, often coordinated by a paediatrician or clinical geneticist. Genetic counsellors can provide essential information about the condition, its inheritance, and support options. While there are no specific dietary or lifestyle interventions to treat the underlying genetic cause, a healthy lifestyle supporting general well-being is always encouraged.
UK care pathway
In the UK, individuals with suspected or diagnosed 1p36 deletion syndrome are supported through the NHS Genomic Medicine Service (GMS). If clinical features suggest a genomic disorder, a healthcare professional, often a paediatrician, may refer for genomic testing. This typically falls under relevant NHS R-codes which define the genetic tests available for specific clinical presentations.
Following a diagnosis, ongoing care is generally managed by a team of specialists, often coordinated by a clinical geneticist. Individuals and their families will have access to genetic counselling services, which provide information, support, and help in understanding the genetic implications of the condition. Support groups and charities also play a vital role in providing peer support and additional resources.
Frequently asked questions
What caused my child's 1p36 deletion syndrome?
In most cases, 1p36 deletion syndrome is a 'de novo' event, meaning the deletion occurred by chance during the formation of the egg or sperm cell, or during early embryonic development. It is usually not inherited from either parent.
Will 1p36 deletion syndrome affect my other children or future pregnancies?
If the deletion occurred spontaneously (de novo), the risk to future children is very low. However, in rare instances, it can be inherited from a parent who carries a 'balanced translocation.' Genetic counselling can assess this risk accurately and provide family-specific information.
What kind of support is available for individuals with 1p36 deletion syndrome?
Support programmes typically include early intervention therapies such as physiotherapy, occupational therapy, and speech and language therapy. Medical specialists like cardiologists or neurologists may also be involved. In the UK, the NHS provides access to these services, often coordinated by a paediatrician or clinical geneticist.
Is there a cure for 1p36 deletion syndrome?
Currently, there is no cure for 1p36 deletion syndrome. Management focuses on addressing the specific symptoms and developmental challenges through various therapies, medical treatments for associated conditions, and ongoing support to improve quality of life.
How common is 1p36 deletion syndrome?
1p36 deletion syndrome is considered a rare condition, affecting approximately 1 in 5,000 to 10,000 live births. It is one of the most common terminal deletion syndromes.
References
- Slavotinek A, Shaffer LG, Shapira SK. Monosomy 1p36. Journal of medical genetics. 1999. PMID: 10507720
- Jacquin C, Landais E, Poirsier C. 1p36 deletion syndrome: Review and mapping with further characterization of the phenotype, a new cohort of 86 patients. American journal of medical genetics. Part A. 2023. PMID: 36369750
- Gajecka M, Mackay KL, Shaffer LG. Monosomy 1p36 deletion syndrome. American journal of medical genetics. Part C, Seminars in medical genetics. 2007. PMID: 17918734
- Jordan VK, Zaveri HP, Scott DA. 1p36 deletion syndrome: an update. The application of clinical genetics. 2015. PMID: 26345236
- Radio FC, Pang K, Ciolfi A. SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females. American journal of human genetics. 2021. PMID: 33596411
- Rocha CF, Vasques RB, Santos SR. Mini-Review: Monosomy 1p36 syndrome: reviewing the correlation between deletion sizes and phenotypes. Genetics and molecular research : GMR. 2016. PMID: 26910004
- Battaglia A. Del 1p36 syndrome: a newly emerging clinical entity. Brain & development. 2005. PMID: 16023552
- Adam MP, Bick S, Mirzaa GM. 1p36 Deletion Syndrome – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1993. PMID: 20301370