2026 ECNP Congress

EP01-1079

Atomoxetine response after methylphenidate intolerance in a child with Basilicata-Akhtar syndrome and attention-deficit/hyperactivity disorder

Hale Betul Furuncu — S. Bozduman Çelebi, A. Arıcı Gürbüz · University of Health Sciences- Başakşehir Çam and Sakura City Hospital, Child and Adolescent Psychiatry, İstanbul, Türkiye

2026 ECNP Congress

Introduction

Basilicata-Akhtar syndrome is a rare X-linked neurodevelopmental disorder caused by pathogenic variants in the MSL3 gene and associated with impaired histone H4 lysine 16 acetylation [1]. It is characterised by global developmental delay, language impairment, hypotonia and variable behavioural manifestations [1,2]. Although attention-deficit hyperactivity disorder (ADHD) may be part of the neurobehavioural phenotype, evidence regarding pharmacological management of ADHD symptoms in MSL3-related disorders remains extremely limited [2,4]. We present a child with Basilicata-Akhtar syndrome who developed methylphenidate intolerance and subsequently benefited from atomoxetine.

Case Presentation

A 6-year-old male patient was referred to our child and adolescent psychiatry outpatient clinic due to developmental delay, attention difficulties, hyperactivity, impulsivity and behavioural problems causing marked academic and social functional impairment. Developmental history revealed delays in motor and language domains. He achieved unsupported sitting at 9 months and independent walking at approximately 18 months. His first meaningful words emerged around 3 years of age, and expressive language remained markedly delayed. Cognitive assessment using the Kent-EGY and Porteus Maze tests could not be completed because of poor cooperation, attentional difficulties and fine motor limitations. Based on developmental history, adaptive functioning and clinical evaluation, the patient was diagnosed with moderate intellectual disability according to DSM-5 criteria.

Neurological evaluation revealed no history of epilepsy, and both EEG and brain MRI findings were normal. Autism spectrum disorder was clinically excluded according to DSM-5 criteria. The patient met DSM-5 diagnostic criteria for ADHD based on comprehensive clinical evaluation, supported by parent- and teacher-reported rating scales (Turgay DSM-IV-based scale) . Genetic testing identified a pathogenic variant in the MSL3 gene, confirming Basilicata-Akhtar syndrome.

Baseline ADHD symptom severity was rated as severe using the Clinical Global Impression-Severity scale (CGI-S = 5). Methylphenidate was titrated to 20 mg/day using a modified-release formulation; however, it was discontinued due to treatment-emergent abdominal pain and increased irritability. Pharmacotherapy was switched to atomoxetine, which was titrated to 36 mg/day. At the one-month follow-up,improvements were observed in hyperactivity, impulsivity, attentional regulation and daily functioning. Post-treatment assessment showed a Clinical Global Impression-Improvement score of 3, indicating that the patient was minimally improved. The CGI-Efficacy Index indicated a moderate therapeutic effect without clinically significant side effects.

Discussion

Consistent with the classical phenotype reported in the literature, the patient exhibited early-onset speech and motor delays accompanied by hypotonia [1,2]. This case supports the growing recognition of a broad neurobehavioural phenotype in MSL3-related disorders and suggests that ADHD may be a clinically significant and treatable comorbidity [2,4]. It also illustrates that stimulant treatment may be limited by tolerability in rare neurodevelopmental syndromes, while atomoxetine may be a useful alternative when methylphenidate is poorly tolerated.

Conclusions

In conclusion, this case supports attention-deficit/hyperactivity disorder as a clinically relevant and treatable comorbidity within the phenotypic spectrum of Basilicata-Akhtar syndrome. Systematic ADHD assessment may inform clinical follow-up and individualised treatment planning in MSL3-related disorders. Careful monitoring of response and tolerability is essential where evidence-based guidance remains scarce.

References

  1. Basilicata, M.F., Bruel, A.-L., Semplicio, G., Keller Valsecchi, C.I., Aktaş, T., Duffourd, Y., Rumpf, T., Morton, J., Bache, I., Szymanski, W.G., et al., 2018. De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation. Nature Genetics, 50, 1442–1451.
  2. Brunet, T., McWalter, K., Mayerhanser, K., et al., 2021. Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder. Genetics in Medicine, 23(2), 384–395.
  3. Kulkarni, V., Chalipat, S., Gupta, A., et al., 2024. Basilicata-Akhtar syndrome: unraveling an ultrarare cause of developmental delay. Cureus, 16(8), e67041.
  4. Qing, Y., Hu, F., Su, W., et al., 2025. Two Chinese patients with Basilicata-Akhtar syndrome caused by novel MSL3 variants: a case report and literature review. Translational Pediatrics, 14(10), 2801–2809.