Genitopatellar syndrome

Overview

Genitopatellar syndrome (GPS) is an extremely rare genetic disorder characterized by a range of developmental abnormalities affecting the genitalia, knees, brain, and other organ systems. The condition is congenital and usually evident at birth. Key features include absent or underdeveloped kneecaps (patellae), genital anomalies, intellectual disability, agenesis of the corpus callosum (a brain structure), and distinctive facial features. Due to the multisystem involvement, individuals with GPS often experience delayed physical and neurological development.

Causes

Genitopatellar syndrome is caused by mutations in the KAT6B gene, which provides instructions for producing a protein involved in regulating gene expression and development. These mutations typically occur de novo, meaning they arise spontaneously and are not inherited from the parents. The condition follows an autosomal dominant pattern of inheritance, but in most known cases, there is no family history due to the de novo nature of the mutations.

Symptoms

The signs and symptoms of Genitopatellar syndrome vary in severity but may include:

Musculoskeletal Features:

• Absent or hypoplastic patellae (kneecaps)

• Joint contractures (stiff joints)

• Clubfoot or other lower limb deformities

• Hip dislocation

Genital and Urinary Anomalies:

• Undescended testes (cryptorchidism) in males

• Small or absent genitalia

• Kidney malformations or hydronephrosis

Neurological and Developmental Features:

• Intellectual disability

• Corpus callosum agenesis or hypoplasia

• Seizures

• Delayed speech and motor development

Craniofacial and Other Features:

• Prominent forehead

• Down-slanting palpebral fissures (eye openings)

• High-arched palate

• Feeding difficulties in infancy

Diagnosis

Diagnosis of Genitopatellar syndrome is typically made based on clinical findings and confirmed through genetic testing:

• Clinical evaluation: Based on recognizable physical and developmental features

• Radiological imaging: X-rays may reveal absent patellae and skeletal anomalies

• Brain MRI: To identify structural brain abnormalities such as agenesis of the corpus callosum

• Ultrasound: To assess kidney and genital abnormalities

• Genetic testing: Identification of a pathogenic variant in the KAT6B gene confirms the diagnosis

Treatment

There is no cure for Genitopatellar syndrome, and treatment is supportive and multidisciplinary, focusing on improving quality of life and addressing specific symptoms:

• Orthopedic care: Management of joint contractures, clubfoot, and other skeletal abnormalities through physical therapy, bracing, or surgery

• Neurological management: Anticonvulsants for seizure control and developmental therapies

• Urological and surgical interventions: Correction of genital anomalies or urinary tract issues

• Speech and occupational therapy: To assist with developmental delays and feeding issues

• Regular monitoring: Surveillance of kidney function, growth, and neurological development

• Nutritional support: For infants with feeding difficulties

Prognosis

The prognosis for individuals with Genitopatellar syndrome depends on the severity of the symptoms and associated complications. Many children face significant developmental delays and physical challenges, but with coordinated care, some progress in mobility, communication, and daily functioning can be achieved. The condition is lifelong, and affected individuals typically require continuous medical and therapeutic support. Prognosis may be guarded in severe cases involving major organ involvement or profound neurological impairment.