Rett Syndrome

Rett syndrome is a rare genetic neurological and developmental disorder that affects the way the brain develops. This disorder causes a progressive loss of motor skills and language. Rett syndrome primarily affects females. Most babies with Rett syndrome seem to develop as expected for the first six months of life.

Rett Syndrome primarily affects females because it's caused by mutations in the MECP2 gene on the X chromosome; females have two X chromosomes, one often acting as a "backup," while males (XY) only have one X, meaning a mutation is usually fatal, leading to severe, early-onset illness or miscarriage, with milder forms rare and typically linked to extra X chromosomes (like Klinefelter's), explaining why girls develop symptoms but often survive, unlike most males.

Rett syndrome - Symptoms & causes - Mayo Clinic

Rett syndrome: MedlinePlus Genetics

Key Inheritance Patterns:

• Spontaneous (Most Common):

Over 99% of cases arise from new mutations (de novo) in the MECP2 gene, not passed down through generations.

• X-Linked Dominant:

The mutated gene is on the X chromosome, and one copy is enough to cause the condition.

• Maternal Carrier (Rare Familial):

A mother who is a carrier (with one normal and one mutated X chromosome) can pass it to her children.

• Lethal in Males:

Due to males having only one X chromosome (XY), a mutation in MECP2 is often lethal, causing death in infancy or before birth (MECP2-related severe neonatal encephalopathy).

• Females Affected:

Females (XX) are typically affected because they have a second X chromosome, and in one of the cells, the normal X chromosome can compensate, though severity varies.

In Summary:

Think of it as a genetic "accident" in most cases, but when it is inherited, it's dominant and tied to the X chromosome, making it predominantly a female disorder, while male infants with the mutation rarely survive.