Genitopatellar syndrome

Did You Know?

• The first reported case was a 4-year-old boy described in 1988 by Goldblatt et al.
• In 2000, Cormier-Daire et al. reported seven patients with genital anomalies, facial dysmorphism, kidney anomalies, absent patellae, and severe intellectual disability.
• The Say-Barber-Biesecker variant of Ohdo syndrome, which has many overlapping features, can also be caused by heterozygous mutation in the KAT6B gene.

Signs and symptoms

Major features include patellar hypoplasia or agenesis, flexion contractures at the hips and knees, agenesis of the corpus callosum with microcephaly, hydronephrosis or multiple kidney cysts, atrial septal defect, intestinal malrotation, talipes equinovarus, and feeding difficulties. Additional features may comprise dental anomalies, hearing loss, thyroid anomalies, anal anomalies, hypotonia, and global developmental delay or intellectual disability.

Cause

Genitopatellar syndrome is inherited in an autosomal dominant manner. The responsible mutation occurs in the KAT6B gene, located on the long arm of chromosome 10 (10q22.2). The gene product is a histone acetyltransferase enzyme that regulates early development. Researchers suspect that mutations near the end of the gene produce a shortened enzyme that alters regulation of other genes, though the precise mechanism is not yet proven.

Diagnosis

Clinical diagnostic criteria are not fully defined, but individuals with two major features or one major and two minor features are likely to have a KAT6B mutation. The primary diagnostic method is molecular genetic testing. Additional evaluations include developmental specialist assessment, feeding evaluation, baseline hearing evaluation, thyroid function tests, evaluation for cryptorchidism in males, orthopedic evaluation, hip X-rays, kidney ultrasound, echocardiogram, evaluation for laryngomalacia, and gastroenterologist consultation if bowel malrotation is suspected.

Treatment

There is no cure for genitopatellar syndrome, but treatments address individual symptoms. Educational intervention and speech therapy beginning in infancy can help reduce motor, cognitive, speech, and language delay. Orthopedic referral may be considered for surgical release of contractures, and early physical therapy can improve joint mobility. Thyroid hormone replacement may be used for thyroid dysfunction.