At 1 year, May* wasn’t progressing in her language and motor skills at the same rate she was in her early months. Over the next few months, words she’d proudly said — “mama,” “ball,” “bye-bye” — faded away, and she fumbled her toys. May’s family and her health providers searched for answers. Months passed. By the time May received a referral for genetic testing, after suspicion of RTT by a specialist, she was nearly 2 years old. For families like May’s, each delay represents more than lost time — it is lost opportunity for understanding, support, planning and managing. That is the nightmare caregivers and patients have described when facing RTT. RTT is rare, but that does not mean that it is invisible.¹ For families like May’s and others living with RTT, early recognition, diagnosis, and professional guidance along the way are the difference between confusion and clarity, between isolation and coordinated care.

*Hypothetical patient based on patient experiences and medical literature.

Act Early to Support Timely Diagnosis

• RTT is a complex neurodevelopmental disorder that often presents subtly at first, with hallmark features emerging over time. The diagnosis of RTT is based on clinical symptoms and signs. Typical RTT is characterized by developmental regression and presence of the following core features: loss of spoken language, loss of purposeful hand use, gait abnormalities and stereotyped hand movements (e.g., wringing or washing or mouthing). The period of regression is followed by a stabilization phase in which some skills may partially return.^1,2 Atypical RTT involves at least two of these four core features and five of 11 supportive criteria (e.g., small, cold hands and feet; breathing disturbances when awake; diminished pain response; impaired sleep; bruxism).¹ Overlapping features with conditions like autism spectrum disorder, cerebral palsy, Angelman syndrome, developmental delay or other specific genetic syndromes can obscure early recognition³
• Widespread implementation of genetic testing, along with enhanced developmental screening, have contributed to earlier diagnosis of classic RTT over the last two decades. Even with these advances, the median age for atypical RTT diagnosis still lags behind classic RTT diagnosis by more than 1 year⁴
• Geneticists and genetic counselors (GCs) are uniquely positioned to help gather information that may support a diagnosis, empower frontline providers to initiate appropriate testing, and prepare families for the range of possibilities that genetic results may reveal. Collaboration across specialties and GC involvement may reduce the emotional toll on families searching for answers.⁵

Guiding Families Through the Genetic Testing Landscape and Beyond

• In most patients with RTT, a mutation in the MECP2 gene is identified. Severity of RTT signs and symptoms vary by mutation type and location, but other genetic factors may also play a role (e.g., skewing of X-chromosome inactivation). Clinical presentation can vary even among patients carrying the same MECP2 gene mutation. When RTT is suspected in a child, genetic sequencing and deletion/duplication analysis should be performed.¹
• For individuals under 3 years old with clinical features suggestive of RTT but no loss of skills, a diagnosis of possible RTT is often given — especially since mutations can now be identified in some individuals before any clear regression. These individuals should be reassessed periodically for regression. If regression occurs, the diagnosis can be changed to definite RTT. If no regression is evident by the age of 5, the RTT diagnosis should be reconsidered.²

Providing Perspectives Throughout the Journey

• GCs are well-positioned to be part of a coordinated care team that might include geneticists, neurologists or other specialists. GCs thus have a critical role to support families with RTT well beyond diagnosis:^1,5
  • Understanding the concerns of the parents/family
  • Interpreting genetic testing results, explaining the significance of the genetic findings
  • Counseling the family (e.g., explain the concept of de novo vs inherited genetic disorders)
  • Connecting to family and professional organizations
  • Providing information about clinical trials
  • Guiding proactive management of comorbidities
  • Reducing unnecessary testing
  • Providing a framework of what the family might expect in the future (e.g., the risk of epilepsy, gastrointestinal problems, sleep issues, anxiety and orthopedic issues)

Practical Takeaways for GCs: 3 Ways to Strengthen RTT Care

1. Act early: When clinical features are first observed, advocate for prompt and comprehensive genetic testing.
2. Guide families: Use anticipatory counseling to help families understand potential results, next steps in testing and what to expect in ongoing multidisciplinary care.
3. Provide perspectives and ongoing support to help families navigate RTT and uncertainties ahead.

References

1. Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatr Open. 2020;4(1):e000717. doi:10.1136/bmjpo-2020-000717
2. Neul JL, Kaufmann WE, Glaze DG, et al; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68(6):944-950. doi:10.1002/ana.22124
3. Hunter K. The Rett Syndrome Handbook. 2nd ed. International Rett Syndrome Association; 2007.
4. Tarquinio DC, Hou W, Neul JL, et al. Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis. Pediatr Neurol. 2015;52(6):585-591.e2. doi:10.1016/j.pediatrneurol.2015.02.007
5. Savatt JM, Myers SM. Genetic testing in neurodevelopmental disorders. Front Pediatr. 2021;9:526779. doi:10.3389/fped.2021.526779