Review Question - QID 212939

The patient has scoliosis with a C-shaped curve and a MECP2 mutation, which are associated with Rett syndrome. Rett syndrome is inherited in an X-linked dominant fashion.

Rett syndrome is an X-linked dominant disorder that affects the grey matter of the brain. It results from a MECP2 gene mutation, which encodes the methyl-CpG-binding protein-2 that methylates DNA. Males affected with Rett syndrome fail to make it to term, while females survive and manifest disease. Patients with Rett syndrome may exhibit developmental delays, behavioral abnormalities (screaming and crying, loss of speech), seizures, and GI issues such as constipation. From an orthopedic standpoint, they may experience spasticity and joint contractures, ataxia, hypotonia, and scoliosis. Scoliosis in Rett syndrome occurs in >50% of patients and presents by the age of 10 years old with a C-shaped curve that is not responsive to bracing.

Sirianni et al. published a case report on a Brazilian family with 3 daughters showing clinical features characteristic of Rett syndrome. They demonstrated X-linked dominant inheritance and localized the responsible locus to Xq28. They also showed that individuals may be non-penetrant carriers of Rett syndrome due to X inactivation.

Van der Veyver et al. published a study on the genetic basis of Rett syndrome. They discovered mutations in MECP2, the gene that encodes the transcriptional repressor, methyl-CpG-binding protein 2. They report that nonsense, missense, or frameshift mutations have been found in at least 80% of girls affected with classic Rett syndrome, but that there is no clear correlation between the type and position of the mutation and the phenotypic features of classic and variant Rett syndrome patients.

Figure A is an AP and lateral radiograph of the spine demonstrating scoliosis with a C-shaped curve.

Incorrect Answers:
Answers 1, 3, 4, and 5: Rett syndrome is inherited in an X-linked dominant fashion.