Clinical Variability in MECP2 Duplication Syndrome: Highlighting Sialorrhea as the Daily Challenge

We present the case of a 10-year-old boy diagnosed with MECP2 duplication syndrome, carrying a 211 kb duplication at Xq28 (153194797_153406233) (GRCh37/hg19). Despite the underlying genetic condition, his overall developmental course has been relatively favorable. He achieved ambulation, though with a clumsy gait, and has shown progressive motor improvements. At the age of 9, he sustained a tibia and fibula fracture after an accidental fall, but recovered gradually with the aid of intensive rehabilitation.

In terms of communication, he demonstrates good social intent through vocalizations, pointing, and gestures, and is described as affectionate and sociable. Notably, he has never experienced epileptic seizures, which contributes to a less severe clinical outlook compared to many patients with MECP2 duplication syndrome.

One of the most disabling symptom affecting his daily life is severe, treatment-refractory sialorrhea. Multiple approaches have been attempted: physical measures, pharmacological treatment with trihexyphenidyl (Artane)—which had poorly tolerated side effects such as constipation—and botulinum toxin injections, which provided only partial benefit.

This case illustrates how, in the context of a potentially severe genetic disorder, the factor most limiting quality of life and social interactions may not necessarily be neurological regression or seizures, but rather excessive drooling. The lack of consistently effective therapies without significant side effects underscores an unmet need in the management of this challenging symptom.