SNP Shot: Genomic Insights

Rett syndrome is a neurological disorder primarily affecting females. The most prevalent type is called classic Rett syndrome. Girls with this condition typically experience 6 to 18 months of seemingly normal development after birth, followed by the onset of significant difficulties with language, communication, learning, coordination, and other cognitive functions. A hallmark of the condition is the loss of purposeful hand use early in childhood, replaced by repetitive hand movements like wringing, washing, or clapping. Affected girls often exhibit slower growth rates and, in approximately 75% of cases, have a smaller than average head size (microcephaly). Additional signs and symptoms can include breathing irregularities, spitting up or excessive drooling, abnormal eye movements such as intense staring or frequent blinking, cold extremities, irritability, sleep problems, seizures, and scoliosis (an abnormal curvature of the spine).

Researchers have identified several variant or atypical forms of Rett syndrome, which can present with symptoms that are either milder or more severe compared to the classic form.

Rett syndrome is classified within a spectrum of disorders sharing the same genetic origin. Other conditions within this spectrum include PPM-X syndrome, MECP2 duplication syndrome, and MECP2-related severe neonatal encephalopathy. Notably, these other conditions can affect males.

Inheritance:

In the vast majority (over 99%) of Rett syndrome cases, there is no family history of the disorder. These instances are typically attributed to new mutations in the MECP2 gene. While rare, some families have multiple affected members. These cases have been instrumental in establishing that classic Rett syndrome and its variants, when caused by MECP2 gene mutations, follow an X-linked dominant inheritance pattern. X-linked inheritance signifies that the mutated gene responsible for the disorder is located on the X chromosome, one of the sex chromosomes. Dominant inheritance means that only one copy of the altered gene in each cell is enough to cause the condition. Males with MECP2 gene mutations often do not survive infancy. However, a small number of males with specific MECP2 genetic changes have presented with symptoms similar to Rett syndrome, including intellectual disability, seizures, and motor impairments. In males, this condition is termed MECP2-related severe neonatal encephalopathy. Some males with MECP2 gene mutations exhibit milder symptoms within the spectrum of the disorder.