Genitopatellar syndrome

Genitopatellar syndrome is a rare disorder with characteristic craniofacial features, congenital flexion contractures of the lower limbs, absent or abnormal patellae, urogenital anomalies, and severe psychomotor retardation. In 2012, it was shown that mutations in the gene KAT6B cause the syndrome.

Signs and symptoms

Genitopatellar syndrome is characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability and abnormalities affecting other parts of the body. It is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an unusually small head (microcephaly) and structural brain abnormalities, including agenesis of the corpus callosum.

Major features include:

• Patellar hypoplasia/agenesis
• Flexion contractures at the hips and knees (including club feet)
• Agenesis of the corpus callosum with microcephaly
• Hydronephrosis and/or multiple kidney cysts

Minor features include:

• Dental anomalies (delayed eruption of teeth)
• Hearing loss
• Thyroid anomalies
• Anal anomalies
• Hypotonia
• Global developmental delay/intellectual disability

Cause

Genitopatellar syndrome is inherited in an autosomal dominant fashion. The mutation responsible for the syndrome occurs in the KAT6B gene. This gene is located on the long arm of chromosome 10 (10q22.2).

The KAT6B gene gene product is an enzyme called histone acetyltransferase which functions in regulating and making of histone which are proteins that attach to DNA and give the chromosomes their shape. The function of histone acetyltransferase produced from KAT6B is unknown but it is considered as a regulator of early development. There is little known about how the mutation in the KAT6B causes the syndrome but researchers suspects that the mutations occur near the end of the KAT6B gene and causes it to produce shortened acetyltransferase enzyme. The shortened enzyme alters the regulation of other genes. On the other hand, the mutation of KAT6B leading to the specific features of genitopatellar syndrome is still not surely proven.

Diagnosis

Even though clinical diagnostic criteria have not been 100 percent defined for genitopatellar syndrome, the researchers stated that the certain physical features could relate to KAT6B mutation and result in the molecular genetic testing. The researchers stated that the Individuals with two major features or one major feature and two minor features are likely to have a KAT6B mutation. To diagnose the Genitopatellar Syndrome, there are multiple ways to evaluate. Medical genetics consultation

• Evaluation by developmental specialist
• Feeding evaluation
• Baseline hearing evaluation
• Thyroid function tests
• Evaluation of males for cryptorchidism
• Orthopedic evaluation if contractures are present or feet/ankles are malpositioned
• Hip X-rays to evaluate for femoral head dislocation
• Kidney ultrasound examination for hydronephrosis and cysts
• Echocardiogram for congenital heart defects
• Evaluation for laryngomalacia if respiratory issues are present
• Evaluation by gastroenterologist as needed, particularly if bowel malrotation is suspected

Treatment

There is no cure for genitopatellar syndrome. However, there are treatments for the different symptoms. For the developmental symptoms, Educational intervention and speech therapy beginning in infancy could help to reduce the high risk for motor, cognitive, speech, and language delay. For the skeletal features, referral to an orthopedist for consideration of surgical release of contractures. In addition, early referral to physical therapy could help increase joint mobility. Lastly, thyroid hormone replacement could help out the thyroid dysfunction.

History

In 1988, Goldblatt et al. first reported a 4-year-old boy with hypoplastic patellae, mental retardation, scrotal hypoplasia, skeletal deformities, kidney anomalies, flattened nasal bridge, and short stature. Later in 2000, Cormier-Daire et al. reported seven patients with genital anomalies (scrotal hypoplasia and cryptorchidism in the boys and clitoral hypertrophy in the girls), facial dysmorphism, kidney anomalies, absent patellae, and severe mental retardation in the two survivors. The condition is now known as genitopatellar syndrome.

See also

• Say-Barber-Biesecker-Young-Simpson syndrome

External links

Classification	ICD-10: Q87.8 OMIM: 606170 DiseasesDB: 35131
External resources	Orphanet: 85201

NIH genetic and rare disease info

• NIH info on Genitopatellar syndrome

Genitopatellar syndrome is a rare disease.