Efficacy of risperidone and behavioral delineation in METTL5-related syndrome: a pooled analysis of literature and report of a novel variant
Acta Neurologica Belgica, cilt.126, sa.4, ss.1347-1354, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 126 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s13760-026-03084-y
- Dergi Adı: Acta Neurologica Belgica
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.1347-1354
- Anahtar Kelimeler: METTL5, Neurodevelopmental disorder, Microcephaly, Risperidone, Behavioral dysregulation, Literature review
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Background: METTL5-related neurodevelopmental disorder is a rare autosomal recessive condition characterized by primary microcephaly, intellectual disability, and variable neurobehavioral manifestations. While the genetic etiology is well-established, targeted pharmacological management for the severe neuropsychiatric components of the syndrome remains undefined. Methods: We conducted a comprehensive literature review of all published METTL5 cases to analyze the phenotypic spectrum, with a specific focus on behavioral dysregulation. Concurrently, we evaluated the clinical and pharmacological course of an index patient from Türkiye harboring a novel homozygous frameshift variant [NM_014168.4:c.415_416del; p.(Met139Glyfs*23)]. Results: Analysis of the pooled cohort (n = 16) confirms that primary microcephaly and moderate-to-severe intellectual disability are universal features. Crucially, profound behavioral abnormalities—including attention-deficit/hyperactivity disorder (ADHD), impulsive aggression, and severe self-mutilation—emerge as highly prevalent core characteristics, documented in over 90% of cases. The index patient exhibited severe ADHD and episodic aggression alongside a distinct, previously unrecognized craniofacial dysmorphic profile. Targeted intervention with low-dose risperidone (0.25 mg/day) yielded a rapid and robust reduction in impulsivity and behavioral dysregulation, directly facilitating her active engagement in multidisciplinary rehabilitative therapies. Conclusions: This study expands the genotypic and phenotypic spectrum of METTL5 deficiency and underscores its significant neurobehavioral burden. Our preliminary clinical observation suggests that atypical antipsychotics, such as risperidone, may represent a potential therapeutic option for managing the challenging behavioral components of this disorder, although further studies are needed to confirm these findings.