What are the other Names for this Condition? (Also known as/Symptoms)

• Absent Patellae, Scrotal Hypoplasia, Renal Anomalies, Facial Dysmorphism, and Mental Retardation
• GPS (Genitopatellar Syndrome)
• GTPTS (Genitopatellar Syndrome)

What is Genitopatellar Syndrome? (Definition/Background Information)

• Genitopatellar Syndrome (GPS) is an extremely rare and newly-reported genetic disorder. It is caused by mutations in the KAT6B gene. This gene resides on chromosome 10 and codes for a type of enzyme known as histone acetyl transferase, which appears to play a crucial role in the early development of bone and nerves
• Genitopatellar Syndrome has an autosomal dominant inheritance trait, where a single copy of the mutated gene is sufficient to cause the disorder. However, it must be noted that in all of the reported cases, no family history of GPS is known. The mutation causing the disorder appears to be within the affected individuals, and occurs as a result of ‘new’ mutations
• The chief symptoms of Genitopatellar Syndrome include missing kneecaps, genital abnormalities (such as underdeveloped scrotum in males and enlarged clitoris in females), abnormal facial structures (such as protruding or receding chin and narrowing of the head at the temples), delay in achieving developmental milestones and mental retardation
• Some potential complications ensuing from Genitopatellar Syndrome are breathing problems, feeding issues, and abnormalities in internal organs such as the heart and kidneys
• Currently, no diagnostic criteria exist for Genitopatellar Syndrome and it is still being evaluated. A healthcare professional may be able to suspect the condition based on some characteristic features of disease manifestation. When GPS is suspected, genetic testing for KAT6B gene mutations may be recommended for confirmation
• A team of healthcare professionals and specialists may need to be involved for the diagnosis of conditions affecting different organs. Additionally, it is has been reported that traits of this condition may be recognized through ultrasound imaging of the fetus during pregnancy
• Treatment options for Genitopatellar Syndrome are geared toward addressing the symptoms in order to offer relief to the affected individual or child
• There are no methods or guidelines for preventing Genitopatellar Syndrome at the present time. Genetic testing and ultrasound imaging of fetus during pregnancy may offer some information regarding the disorder
• The prognosis of Genitopatellar Syndrome is poor. Children with GPS typically die from the condition during the first 12 months in most cases

Who gets Genitopatellar Syndrome? (Age and Sex Distribution)

• Genitopatellar Syndrome is reported to occur in less than than 1 individual per million. So far, about 18-20 cases of this syndrome have been reported in the medical literature
• GPS is a congenital disorder that is manifested at birth
• Both genders are affected by this disorder and no male-female preference is seen
• All racial and ethnic groups are at risk for GPS

What are the Risk Factors for Genitopatellar Syndrome? (Predisposing Factors)

• Currently, no risk factors have been identified for the genetic disorder Genitopatellar Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Genitopatellar Syndrome? (Etiology)

Genitopatellar Syndrome is caused by mutations in the KAT6B gene on chromosome 10.

• KAT6B has the genetic codes for histone acetyltransferase, an enzyme that adds acetyl molecules to histone proteins (structural proteins that bind to DNA to form ordered structures called nucleosomes, these also play a role in gene regulation)
• Although not much is known about the function of histone acetyltransferases, scientists believe that these enzymes may play a role in regulating genes during early development of bones and nerves
• Additionally, KAT6B mutations are reported to be at the end of the gene causing a shorter version of the enzyme. Scientists hypothesize that this may lead to the enzyme having a faulty function and consequent abnormal gene regulation, leading to the disorder (although the events leading up to the characteristics of GPS are yet unclear)

The pattern of inheritance of Genitopatellar Syndrome is autosomal dominant. However, no family history of the disorder exists; new mutations are said to arise spontaneously in the affected individuals.

What are the Signs and Symptoms of Genitopatellar Syndrome?

The signs and symptoms of Genitopatellar Syndrome may include:

• Related to the skeletal system:
  • Patellar hypoplasia or patellar agenesis; a lack of well-developed or even missing kneecaps
  • Contractures - joint deformities in the hips, knees
  • Clubfeet
  • Abnormalities in collar bones, pelvic bone, ribs and spine
• Related to the genital system:
  • In males: Cryptorchidism (undescended testes) and underdeveloped scrotum
  • In females: Clitoromegaly (enlarged clitoris) and small labia
• Abnormal facial features that include:
  • Microcephaly or the presence of unusually small head
  • Prominent cheeks and prominent eyes
  • Micrognathia or very small chin; prognathia or protruding chin
  • Rounded nose; broad nasal bridge
  • Narrow head at the temples
• Related to the brain:
  • Reduction or absence of tissue connecting the two halves of the brain (agenesis of the corpus callosum)
  • Other structural abnormalities in brain
• Developmental abnormalities:
  • Drastically delayed development
  • Severe impairment in intellectual ability
  • Psychomotor retardation (slow thoughts and actions)

Other signs and symptoms of GPS may include:

• Congenital heart defects
• Cysts in kidneys
• Fluid build-up and swelling of kidneys (hydronephrosis)
• Hearing issues or loss of hearing
• Dental problems, delay in emergence of teeth
• Thyroid hormone abnormalities
• Low muscle tone (hypotonia)

How is Genitopatellar Syndrome Diagnosed?

The criteria for the diagnosis of Genitopatellar Syndrome are still being finalized, since this is a (relatively) newly-defined disorder.

• Researchers and scientists have classified the symptoms into major and minor features. When an individual exhibits two major and one minor feature, or two minor and one major feature, it is determined that he/she could have a KAT6B gene mutation
  • Major features include: Kneecap abnormalities, contractures (hip, knees), clubfeet, agenesis of the corpus callosum (missing connection between the brain halves), microcephaly, cysts in kidney, hydronephrosis (urine build-up and kidney swelling)
  • Minor features include: Dental abnormalities, issues with hearing, thyroid hormone problems, developmental delays
• Once GPS is suspected, health professionals from multiple fields may carry out several tests to identify and correct the abnormalities, where possible. These could include blood tests and imaging studies. The team of specialists could consist of the following:
  • Feeding and nutrition specialist
  • Developmental specialist
  • Endocrinologist (hormones such as thyroid hormone)
  • Auditory specialist (hearing)
  • Orthopedic (skeletal and bone abnormalities)
  • Nephrologist (kidneys and their function)
  • Cardiologist (congenital heart defects)
  • Gastroenterologist, if needed
  • Pulmonologist, if needed
• Prenatal diagnosis: Through ultrasound imaging in a pregnant woman, or molecular testing, it is possible to identify features of Genitopatellar Syndrome in the developing fetus

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Genitopatellar Syndrome?

Babies with Genitopatellar Syndrome can have significant complications that can be life-threatening. Some potential complications of GPS may include:

• Breathing problems
• Acute feeding difficulties
• Issues with the heart
• Kidney malfunction

How is Genitopatellar Syndrome Treated?

Currently, there are no treatment measures available for Genitopatellar Syndrome. At this time, options are limited to addressing the signs and symptoms:

• Skeletal defects: Surgery to correct abnormalities, physiotherapy for joint rehabilitation
• Hormonal: Hormone replacement therapy (such as through thyroid hormone)
• Developmental: Speech therapy, special education

How can Genitopatellar Syndrome be Prevented?

Genitopatellar Syndrome is a genetic disorder, and hence, there are no specific methods or guidelines to prevent the condition. A majority of the individuals have sporadic mutations; therefore, currently, it is not possible to prevent GPS.

• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Genitopatellar Syndrome
• Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended

What is the Prognosis of Genitopatellar Syndrome? (Outcomes/Resolutions)

• The prognosis of Genitopatellar Syndrome is poor, with the majority of affected children reportedly succumbing to the condition within the first year
• Children with mild signs and symptoms may have slightly better prognosis than those with severe signs and symptoms

Additional and Relevant Useful Information for Genitopatellar Syndrome:

Histones are the major structural proteins inside the nucleus of a cell, to which DNA binds and forms ordered structures called nucleosomes. The histone proteins are also involved in regulation of gene expression.