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18q deletion syndrome
Also known as monosomy 18q · de Grouchy syndrome type 2 · 18q22-q23 deletion
This syndrome can lead to a range of developmental and physical challenges, including distinctive facial features, intellectual disability, and various health issues. It affects individuals from birth and its severity can vary widely.
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Overview
18q deletion syndrome, also known as monosomy 18q, is a rare genetic condition where a segment of the long arm (q arm) of chromosome 18 is missing. Chromosomes are structures within our cells that carry our genetic information. Humans typically have 23 pairs of chromosomes, and a deletion means a small part of one of these chromosomes is absent [PMID:33678000]. The size and exact location of the missing segment can vary between individuals, which often influences the specific symptoms and their severity. This condition is usually present from birth.
The long arm of chromosome 18 is designated 'q'. Therefore, a deletion on the long arm is referred to as '18q deletion'. The syndrome is sometimes called de Grouchy syndrome type 2, named after the scientist who first described it. While relatively rare, affecting approximately 1 in 40,000 live births, understanding the specific genetic change is crucial for managing the associated health and developmental needs.
Symptoms & clinical features
The clinical features of 18q deletion syndrome can vary considerably among affected individuals, depending on the precise genes lost in the deleted region [PMID:28770788]. Common features often include developmental delays, which can affect motor skills, speech, and cognitive abilities. Intellectual disability is also frequently observed, ranging from mild to more profound.
Physical characteristics may include distinctive facial features such as a small chin (micrognathia), a broad nose, deep-set eyes, and malformed ears. Other potential signs include short stature, foot abnormalities (like clubfoot), and skeletal differences. Some individuals may experience problems with their eyes (e.g., nystagmus, strabismus), hearing difficulties, or heart defects. Gastrointestinal issues and neurological problems, such as seizures or differences in brain structure, have also been reported in some cases [PMID:33678000].
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Affected organs
18q deletion syndrome can affect multiple organ systems. The central nervous system is commonly impacted, leading to developmental delays, intellectual disability, and sometimes structural brain differences or seizures. The skeletal system can be affected, resulting in short stature, foot abnormalities, and other bone-related issues.
Sensory organs are also often involved, with potential for vision impairments (like nystagmus or strabismus) and hearing loss. The heart may have structural defects, and gastrointestinal issues are sometimes present. While less common, kidney anomalies and immunological deficiencies have also been reported in some individuals with this syndrome, highlighting the widespread potential effects of the missing genetic material.
Risks & severity
The severity of 18q deletion syndrome varies widely, largely depending on the size and exact location of the deleted segment on chromosome 18. Larger deletions or deletions involving critical genes tend to be associated with more significant health and developmental challenges. Individuals with this condition typically experience some degree of developmental delay and intellectual disability, but the extent can range from mild learning difficulties to more severe cognitive impairment.
Lifetime risks are challenging to quantify precisely due to the variability of the condition. However, individuals with 18q deletion syndrome may face ongoing medical and developmental needs throughout their lives. Regular medical follow-ups are important to monitor for potential complications affecting the heart, hearing, vision, and other organ systems. Early intervention therapies, such as speech and language therapy, occupational therapy, and physical therapy, can significantly improve developmental outcomes.
Genetic causes
18q deletion syndrome is caused by a missing segment of genetic material on the long arm (q arm) of chromosome 18. This missing piece can vary in size and exact position among affected individuals. This type of genetic change, where a portion of a chromosome is absent, is known as a microdeletion.
One gene located within the commonly deleted region on 18q, and considered significant for the syndrome's features, is TCF4. TCF4 (transcription factor 4) provides instructions for making a protein that plays a critical role in brain development, especially in the formation and function of nerve cells. The TCF4 protein acts as a transcription factor, meaning it helps control the activity of many other genes. A loss of one copy of the TCF4 gene due to an 18q deletion is thought to contribute to some of the cognitive and developmental challenges seen in the syndrome. Other genes in the deleted region are also likely to contribute to the varied clinical picture.
- TCF4 transcription factor 4
Inheritance pattern
Most cases of 18q deletion syndrome are 'de novo', meaning the deletion occurs spontaneously and is not inherited from a parent. In these situations, the genetic change happens by chance during the formation of the egg or sperm cell, or very early in embryonic development. Therefore, typically, neither parent carries the deletion.
In a small number of cases, one parent may carry a 'balanced translocation' involving chromosome 18. In a balanced translocation, genetic material is rearranged but no net gain or loss occurs, so the parent usually does not have symptoms. However, this balanced rearrangement can lead to an unbalanced rearrangement, such as an 18q deletion, in their offspring. If a balanced translocation is identified in a parent, there is an increased risk of recurrence in future pregnancies. Genetic counselling is vital to discuss these risks and options for family planning.
Diagnosis & testing
Diagnosis of 18q deletion syndrome often begins when a child presents with developmental delays, distinctive facial features, or other health concerns that suggest a genetic condition. Clinical geneticists or paediatricians may suspect the syndrome based on these observations. Genetic testing is required to confirm the diagnosis.
The primary diagnostic method is usually a chromosomal microarray (CMA) or karyotyping. CMA is a high-resolution test that can detect small missing (deletions) or extra (duplications) pieces of chromosomal material that are too small to be seen with standard karyotyping. In the UK, such testing is typically accessed through the NHS Genomic Medicine Service (GMS). A referral to Clinical Genetics is generally made by a GP or specialist for assessment and consideration of genetic testing. Relevant NHS R-codes would be used to guide testing panels, depending on the presenting clinical features.
Management & lifestyle
Management of 18q deletion syndrome is multidisciplinary and focuses on addressing the specific symptoms and developmental needs of each individual. There is no cure for the underlying genetic cause, so care is supportive and aims to maximise quality of life. An individualised care plan, often coordinated by a paediatrician or clinical geneticist, is typical.
This may involve early intervention therapies such as speech and language therapy to assist with communication, occupational therapy to develop fine motor skills and daily living activities, and physical therapy for gross motor development. Regular medical surveillance is important to monitor for potential complications, including vision and hearing assessments, cardiac evaluations, and neurological check-ups. Educational support will also be crucial, often involving special educational needs provision. Genetic counselling is an important part of managing the condition, providing information and support to families.
UK care pathway
In the UK, individuals suspected of having a genetic condition like 18q deletion syndrome would typically be referred by their GP or another specialist to a Clinical Genetics service. This service, part of the NHS Genomic Medicine Service (GMS), offers expert assessment, genetic counselling, and access to genomic testing. Diagnostic tests, such as chromosomal microarray, are usually performed in line with national testing guidelines, using specific R-codes from the National Genomic Test Directory. Following diagnosis, individuals and their families will receive ongoing support and information from clinical geneticists and genetic counsellors, guiding them through the implications of the diagnosis and coordinating multidisciplinary care.
Frequently asked questions
What caused my child's 18q deletion syndrome?
Most cases of 18q deletion syndrome happen by chance, meaning the genetic change occurred spontaneously during the formation of reproductive cells or early in development. It is usually not inherited from parents. In rare situations, one parent might carry a balanced chromosomal change that led to the deletion in the child.
Will my future children also have 18q deletion syndrome?
If the 18q deletion in your child was a spontaneous (de novo) event, the risk for future children to have the syndrome is generally very low. If a parent is found to carry a balanced chromosomal rearrangement, the risk might be higher. Genetic counselling is recommended to discuss these risks based on your specific family situation.
What kind of support is available for families in the UK?
In the UK, support often involves a team of healthcare professionals through the NHS, including paediatricians, clinical geneticists, genetic counsellors, and various therapists (speech, occupational, physical). Patient support groups and charities can also provide valuable resources, information, and a community for families affected by rare chromosomal conditions.
How does the size of the deletion affect the condition?
The severity and specific symptoms of 18q deletion syndrome often depend on the amount of genetic material missing and which specific genes are involved. Larger deletions or deletions that include critical genes tend to be associated with more pronounced developmental and health challenges. However, there is still variation even among individuals with similar deletions.
Can 18q deletion syndrome be cured?
There is currently no cure for 18q deletion syndrome because it is caused by a permanent change in the chromosomes. Management focuses on supporting the individual's development and addressing specific symptoms through therapies, medical care, and educational support to improve their quality of life.
References
- Matei MI, Vlad RM. 18q Deletion (de Grouchy Syndrome) in Rural Romania: A Case Report and Healthcare System Challenges. Reports (MDPI). 2025. PMID: 40710875
- Verrotti A, Carelli A, di Genova L. Epilepsy and chromosome 18 abnormalities: A review. Seizure. 2015. PMID: 26552569
- Casto C, Pepe G, Li Pomi A. Hashimoto's Thyroiditis and Graves' Disease in Genetic Syndromes in Pediatric Age. Genes. 2021. PMID: 33557156
- Colijn MA, Crockford DN. 18q Deletion Syndrome-Associated Schizophrenia: A Case Report. Neuropsychobiology. 2024. PMID: 38684151
- Hashiguchi S, Tomomasa D, Nishikawa T. 18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency. Journal of clinical immunology. 2024. PMID: 38896123
- Arai-Ichinoi N, Uematsu M, Sato R. Genetic heterogeneity in 26 infants with a hypomyelinating leukodystrophy. Human genetics. 2016. PMID: 26597493
- Grosso S, Pucci L, Di Bartolo RM. Chromosome 18 aberrations and epilepsy: a review. American journal of medical genetics. Part A. 2005. PMID: 15690352
- Obara K, Inomata T. 18q21.1q21.32 Deletion in a Patient With Juvenile Cerebral Infarction. Cureus. 2023. PMID: 37521594