What Are 17q12 Deletion and Duplication Syndromes?

The term 17q12 refers to a specific location on the long arm of chromosome 17. This segment houses a collection of genes that provide instructions for various aspects of growth and development. Genetic changes within this region, such as the loss (deletion) or gain (duplication) of this DNA, can interrupt typical development and are associated with specific genetic syndromes.

Key Genes Located on 17q12

The 17q12 region contains multiple genes with specific roles. One of the most studied is HNF1B (or TCF2), which provides instructions for a protein active during the embryonic development of the kidneys, pancreas, liver, and genital tract. This protein helps ensure these organs form and function correctly.

Another gene in this region is LHX1. The LHX1 protein is important for the formation of the head and nervous system during early development. It also has a function in the development of the female reproductive tract, specifically the Müllerian ducts that form the uterus and vagina.

The ACACA gene is also located within the 17q12 segment. It provides instructions for an enzyme involved in fatty acid synthesis, a process for energy storage and building cell membranes. Proper regulation of ACACA is part of maintaining the body’s metabolic balance.

17q12 Deletion Syndrome

When the 17q12 segment of the chromosome is missing, it results in 17q12 deletion syndrome. This condition has a highly variable presentation, with features differing significantly among individuals. One of the most common set of features involves the kidneys and urinary tract, with issues ranging from structural abnormalities to the formation of cysts.

The loss of the HNF1B gene is responsible for renal cysts and diabetes syndrome (RCAD). This syndrome combines kidney abnormalities with a form of diabetes known as maturity-onset diabetes of the young type 5 (MODY5).

About half of individuals with a 17q12 deletion experience neurodevelopmental or psychiatric conditions. These can include developmental delays, mild learning disabilities, and an increased likelihood of autism spectrum disorder, schizophrenia, or anxiety. The loss of the LHX1 gene is thought to contribute to these features and to reproductive system anomalies in females, like an underdeveloped uterus or vagina.

17q12 Duplication Syndrome

The presence of an extra copy of the 17q12 chromosomal region leads to 17q12 duplication syndrome. Like the deletion syndrome, its features are widely variable, and some individuals with the duplication may have no apparent symptoms.

Neurodevelopmental and behavioral conditions are common among those with symptoms. Abilities can range from normal to severely impaired, with speech and motor skill delays being frequent. Behavioral conditions may include autism spectrum disorder, aggression, and schizophrenia, while seizures are also a reported feature.

Other physical characteristics can be associated with a 17q12 duplication. An unusually small head size (microcephaly) is seen in about half of individuals. Less frequently, abnormalities of the eyes, heart, or kidneys may occur. The extra copies of genes within the duplicated segment are believed to cause this wide array of outcomes.

Diagnostic Approaches for 17q12 Anomalies

Diagnosing 17q12 deletion and duplication syndromes requires genetic testing. The most effective method is a chromosomal microarray (CMA), a high-resolution test that can detect small missing or extra pieces of DNA that are not visible with a standard karyotype test.

Genetic testing may be recommended when a person shows a combination of associated features, such as specific kidney abnormalities, MODY5, and certain neurodevelopmental disorders. These conditions can also be diagnosed prenatally if an ultrasound reveals certain findings, like abnormal kidneys. A procedure like amniocentesis can then provide a sample for CMA to confirm a diagnosis before birth.

Once an anomaly is identified, testing may be offered to the parents. The deletion or duplication can be inherited, even if a parent shows no symptoms. Determining if the change is inherited or new (de novo) provides information for genetic counseling about the chances of it occurring in future pregnancies.

Managing Health and Development

There is no cure for 17q12 syndromes, so management focuses on addressing specific symptoms with a team of specialists. For those with the deletion, regular surveillance of kidney function and glucose levels is necessary due to risks from the loss of the HNF1B gene. This monitoring often includes blood tests and kidney ultrasounds.

Developmental support is a part of management for both syndromes. This includes speech, physical, and occupational therapy to address delays. Educational support is tailored to an individual’s learning needs through tools like individualized education plans (IEPs), while psychological interventions help manage behavioral conditions.

Genetic counseling is a resource for families to understand the condition’s genetic basis and recurrence risk. Support organizations and patient advocacy groups also play a role by connecting families with others who share similar experiences. These networks provide a community for support and access to current information.