17q12 deletion syndrome is a rare genetic condition characterized by the absence of a small segment of genetic material on chromosome 17. This deletion can lead to a diverse range of physical and developmental features.
Understanding the Genetic Basis
17q12 deletion syndrome arises from a microdeletion on the long arm (q arm) of chromosome 17, specifically at position q12. The deleted segment is typically about 1.4 million DNA building blocks, or 1.4 megabases (Mb), in length. This particular deleted segment usually contains 15 genes. The loss of these genes contributes to the varied features observed in individuals with the syndrome. The region is surrounded by short, repeated DNA sequences, which makes it prone to rearrangements during cell division, leading to either deletions or duplications of this segment.
Common Clinical Manifestations
Individuals with 17q12 deletion syndrome often present with a wide spectrum of clinical features. Developmental delays are common, particularly affecting speech and motor skills. Intellectual disability, ranging from mild to moderate, is also observed in about half of affected individuals.
Structural or functional abnormalities of the kidneys and urinary tract are frequently reported. These can vary from mild issues to severe malformations that may lead to kidney failure. Fluid-filled sacs, known as cysts, in the kidneys are a common finding.
Another notable feature is an increased risk of developing maturity-onset diabetes of the young type 5 (MODY5). This form of diabetes appears in adolescence or early adulthood. The combination of kidney cysts and MODY5 is sometimes referred to as renal cysts and diabetes (RCAD) syndrome.
Neurological and psychiatric conditions are also associated with the syndrome. These can include autism spectrum disorder, which impacts social interaction and communication, as well as schizophrenia, anxiety, and bipolar disorder. Epilepsy, usually mild, can occur in approximately one-third of cases. Less commonly, the syndrome may also affect the eyes, liver, brain, and other body systems. Some females with this deletion may have Mayer-Rokitansky-Küster-Hauser syndrome, characterized by the underdevelopment or absence of the vagina and uterus.
Diagnosis and Confirmation
Diagnosis of 17q12 deletion syndrome often begins with clinical suspicion based on the presence of characteristic symptoms. When a healthcare provider observes a combination of the features associated with the syndrome, they may recommend genetic testing. The wide range of symptoms can make it challenging to identify the condition without specific genetic analysis.
The primary diagnostic method for confirming 17q12 deletion syndrome is typically chromosomal microarray analysis (CMA). This test can detect small missing or extra pieces of chromosomes, including the 1.4 Mb deletion on chromosome 17. Fluorescent in situ hybridization (FISH) may also be used if a specific deletion, like 17q12, is already strongly suspected. These tests work by analyzing an individual’s DNA to identify the missing genetic material. Genetic counseling is an important step both before and after testing to help families understand the implications of the results.
Managing the Syndrome
Management of 17q12 deletion syndrome focuses on addressing the specific symptoms and providing supportive care. A multidisciplinary approach is generally employed, involving various medical specialists. Regular medical monitoring is important, particularly for kidney function and for the early detection and management of diabetes, given the increased risk of MODY5.
Developmental therapies play a significant role in maximizing an individual’s potential. These therapies may include physical therapy to assist with motor skill development, occupational therapy to improve daily living skills, and speech therapy to address language delays. Educational support is also tailored to meet the learning needs of each individual. Management of specific medical issues, such as epilepsy, involves appropriate medication and monitoring. The overall goal of management is to enhance the individual’s quality of life and support their development.
Inheritance Patterns and Family Planning
Most cases of 17q12 deletion syndrome are de novo, meaning the deletion occurs spontaneously and is not inherited from either parent. Approximately 75% of cases arise from these new mutations. However, some individuals with the syndrome can inherit the deletion from an affected parent.
The condition follows an autosomal dominant inheritance pattern. This means that only one copy of the chromosome with the deletion is sufficient to cause the syndrome. For affected individuals who have normal fertility, there is a 50% chance of passing the deletion to each of their offspring. Genetic counseling is highly recommended for affected individuals and their families to understand the recurrence risks for future pregnancies and to explore available reproductive options. In very rare instances, parents with normal blood tests can still have more than one child with the deletion due to germline mosaicism, where the deletion is present in some egg or sperm cells but not in other body cells.