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Familial testicular germ cell tumour
This condition involves a predisposition to testicular cancer that runs in families. It primarily affects males and is caused by inherited genetic changes, leading to an increased lifetime risk of developing germ cell tumours in the testes.
Overview
Familial testicular germ cell tumour refers to cases of testicular cancer that have a clear inherited component, meaning they tend to occur in multiple members of the same family. While testicular cancer is generally rare, affecting about 1 in 200 males in the UK, familial forms are even less common. When two or more close relatives are diagnosed with testicular germ cell tumours, it can suggest an underlying genetic predisposition [PMID:24619421]. This inherited risk means that certain genetic changes are passed down through families, increasing the likelihood of developing these tumours.
Symptoms & clinical features
The primary 'symptom' of familial testicular germ cell tumour is the development of a testicular germ cell tumour itself. Testicular cancer often presents as a painless lump or swelling in one of the testes. Other signs can include a feeling of heaviness in the scrotum, a dull ache in the groin or scrotum, or a sudden collection of fluid in the scrotum [PMID:33671217]. In some cases, the tumour may cause pain or tenderness, but this is less common. It is important for individuals with a family history of testicular cancer to be aware of these potential signs and to perform regular self-examinations.
Video: Is cancer in your genes?
Affected organs
The condition primarily affects the testes, which are the male reproductive glands located in the scrotum. These glands are responsible for producing sperm and male hormones. While the tumour originates in the testes, in more advanced stages, cancer cells can potentially spread to other parts of the body, such as the lymph nodes in the abdomen or lungs. However, the initial site of concern and the focus of preventative measures is typically within the testes.
Risks & severity
Individuals with familial testicular germ cell tumour have a significantly elevated risk of developing testicular cancer compared to the general population. The risk increases with the number of affected relatives and how closely they are related; for example, having an affected brother increases risk more than having an affected uncle [PMID:24619421]. The exact age of onset can vary, but testicular cancer typically occurs in young and middle-aged men, commonly between 15 and 49 years of age. While testicular cancer can be serious if not treated, it generally has a high cure rate, especially when detected early. Severity depends on the stage at diagnosis and the specific type of germ cell tumour.
Genetic causes
Familial testicular germ cell tumour can be linked to pathogenic variants in specific genes, such as DMRT1 and KITLG. The DMRT1 gene plays a crucial role in testicular development and male germ cell differentiation. Pathogenic variants in DMRT1 are thought to disrupt these processes, potentially leading to an increased risk of germ cell tumours [PMID:22095267]. Similarly, the KITLG gene (KIT ligand) is involved in the growth and survival of germ cells. Changes in KITLG may alter these signalling pathways, contributing to an elevated susceptibility to testicular germ cell tumours [PMID:20065013]. These genetic alterations mean that the cells do not develop or behave as they should, increasing the chance of uncontrolled growth.
- DMRT1 doublesex and mab-3 related transcription factor 1
- KITLG KIT ligand
Inheritance pattern
Familial testicular germ cell tumour is typically inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of an altered gene from one parent to have an increased risk of developing the condition. If a parent carries a pathogenic variant, there is a 50% chance with each pregnancy that their child will inherit the variant. The condition can affect males from an affected parent, leading to an increased risk of testicular cancer. Females who inherit the variant are generally unaffected by testicular cancer themselves, but can pass the risk on to their male offspring.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of familial testicular germ cell tumour usually begins with a clinical suspicion based on a personal or family history of testicular cancer. If a testicular mass is found, further investigations typically include ultrasound imaging, blood tests for tumour markers (such as alpha-fetoprotein and human chorionic gonadotropin), and sometimes a biopsy. Genetic testing is used to confirm an underlying familial predisposition, often following a clinical diagnosis in an affected family member. Referral to a clinical genetics service, which can be accessed through NHS Genomic Medicine Service pathways, is usually made by a hospital specialist to discuss genetic testing options. The relevant NHS R-code for germ cell tumours includes R143 (Testicular germ cell tumour) which covers genetic testing for inherited forms.
Management & lifestyle
For individuals identified with an increased genetic risk for familial testicular germ cell tumour, management typically focuses on surveillance and early detection. This can involve educating individuals about self-examination and regular clinical testicular examinations by a healthcare professional. Healthcare providers may discuss the potential benefits and limitations of regular imaging, such as ultrasound, though specific guidelines for surveillance in unaffected carriers can vary. It is important for individuals to have access to a genetic counsellor who can provide personalised risk assessments and support. Management for an actual testicular cancer diagnosis follows standard NHS oncology protocols, including surgery, chemotherapy, and/or radiotherapy, depending on the stage and type of tumour.
UK care pathway
In the UK, suspected cases of inherited cancer predisposition, including familial testicular germ cell tumour, are typically managed through the NHS Genomic Medicine Service. If a family history of testicular cancer is significant, a patient may be referred by their GP or a hospital specialist to a regional Clinical Genetics service. Here, a genetic counsellor or clinical geneticist can offer a detailed risk assessment, discuss the benefits and limitations of genetic testing using relevant NHS R-codes (e.g., R143), and provide information on surveillance and management strategies. The multidisciplinary team approach ensures comprehensive care and support.
Frequently asked questions
What is familial testicular germ cell tumour?
It is an inherited condition where genetic changes passed down in families increase the risk of developing testicular cancer. This means that if several close male relatives have had testicular cancer, there might be an underlying genetic cause.
How is familial testicular germ cell tumour inherited?
It follows an autosomal dominant inheritance pattern. This means only one copy of an altered gene from either parent is enough to increase the risk. If a parent carries the altered gene, there's a 50% chance of passing it to each child.
What should I do if I have a family history of testicular cancer?
If you have a strong family history, it's advisable to speak with your GP. They may refer you to a clinical genetics service where you can discuss your individual risk and consider genetic testing and appropriate surveillance options.
Are there any specific symptoms to watch out for?
The main sign is typically a painless lump or swelling in a testicle, or a feeling of heaviness. While usually painless, any changes in the testes should be checked by a doctor, especially with a family history.
Can females carry the gene for familial testicular germ cell tumour?
Yes, females can carry the altered gene in an autosomal dominant pattern. While they do not develop testicular cancer themselves, they can pass the increased risk on to their male children.
References
- Richie JP. Re: Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. The Journal of urology. 2012. PMID: 22784727
- Rapley EA, Crockford GP, Easton DF. Localisation of susceptibility genes for familial testicular germ cell tumour. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2003. PMID: 12752252
- Kratz CP, Han SS, Rosenberg PS. Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. Journal of medical genetics. 2011. PMID: 21617256