Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012

• Rett syndrome is a neurodevelopmental disorder that affects mainly females.
• It might be possible to diagnose RTT before the classical symptoms become obvious.
• Combinations of disturbing symptoms are often seen before classical symptoms as: autistic traits, placidity, floppiness, teeth grinding, hair pulling, incontinence.
• Consider RTT and MECP2 mutation analysis in girls with ID without dysmorphic features.

Background/PurposeRett syndrome (RTT) is a neurodevelopmental disorder that affects mainly females; it results in multiple disabilities and carries a risk of medical comorbidities. Early diagnosis is important to help establish the best treatment opportunities and preventive care in order to slow down the progression of symptoms. We wanted to test our hypothesis that it is possible to diagnose RTT before the classical symptoms become obvious.MethodsWe analysed development and symptoms before and at the time of the RTT diagnosis, as well as the symptoms that triggered MECP2 mutation analysis, in a cohort of girls with RTT born in Denmark between 2003 and 2012.ResultsTwenty-four girls were included, and 87.5% of these girls were diagnosed when the classical RTT symptoms were recognized. However, parents were concerned about their daughters between 3 and 58 months prior to the RTT diagnosis, and they felt that the professionals did not share their concern in the beginning. When reviewing medical files and questionnaires, we noted that the majority of girls did have combinations of concerning symptoms such as developmental delay and a collection of subtle signs such as autistic traits, placidity, floppiness with suspicion of muscular or mitochondrial diseases, hair pulling, teeth grinding, development of incontinence and problems with initiating movements.ConclusionWe conclude that many individuals with MECP2 mutation exhibit characteristics that should raise suspicion for RTT, prior to evolution of the core clinical criteria. As RTT is a rare disease, it is of importance to constantly educate clinicians for heightened awareness of RTT.