MECP2 Related Disorder; RTT; RTS; cerebroatrophic hyperammonemia

Rett syndrome (RTT), one of the MECP2 gene-related disorders, is a progressive neurologic disease in girls characterized by normal birth and apparently normal psychomotor development during the first six to 18 months of life. The girls then enter a short period of developmental stagnation followed by rapid regression in language and motor skills.

Diagnostic testing: The diagnosis of RTT rests on clinical diagnostic criteria established for the syndrome and/or molecular testing of the MECP2 gene. Molecular genetic testing identifies MECP2 mutations in approximately 80% of females with Rett syndrome.

Physical findings: RTT is characterized by:

• •

  Rapid developmental regression in infancy;

• •

  Loss of purposeful hand movements;

• •

  Screaming fits and inconsolable crying;

• •

  Bruxism (teeth grinding);

• •

  Tremors;

• •

  Loss of speech;

• •

  Gait abnormalities;

• •

  Repetitive stereotypic hand movements;

• •

  Severe intellectual disability;

• •

  Microcephaly;

• •

  Seizures;

• •

  Breathing abnormalities;

• •

  Disturbed sleeping patterns;

• •

  Scoliosis;

• •

  Impaired social interactions or social withdrawal;

• •

  Decreased mobility;

• •

  Muscle weakness;

• •

  Hand and foot deformities;

• •

  Rigidity;

• •

  Spasticity; and

• •

  Dystonia (involuntary muscle contractions).

ICD-9: 270.6

Females with RTT may survive into adulthood, but in a very dependent state. The incidence of sudden, unexplained death is significantly higher than in controls of similar age and may in part be caused by the higher incidence of longer corrected QT intervals, T-wave abnormalities, and reduced heart rate variability.

Currently there is no cure for RTT. Management is mainly symptomatic focusing on optimizing the individual’s abilities and providing psychosocial support for the family.

SUGGESTED PROGRAMMATIC ASSESSMENT*

• •

  Molecular genetic testing with sequence analysis of the MECP2 gene on the X chromosome will identify 80% of individuals with Rett syndrome;

• •

  Additional clinical findings would show a characteristic decline or loss of previously attained developmental milestones (i.e., normal development for 6-18 months, followed by loss of milestones); and

• •

  A description of characteristic motor findings (repetitive hand movements, toe walking or unsteady, wide-based, stiff-legged gait) and severely impaired expressive language.

REMARKS