Dear Editor,
Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder marked by persistent inattention, hyperactivity, and impulsivity. Twin studies indicate a high heritability (74–91%), yet discordance in symptom expression raises questions about epigenetics, intrauterine factors, and perinatal influences.[1] The role of assisted reproductive technology (ART) and maternal genetic conditions in ADHD remains underexplored.
This 6-year-old boy, conceived via in vitro fertilization (IVF) and born preterm (32 weeks), exhibited persistent hyperactivity, impulsivity, and inattention, significantly impairing his academic and social functioning. His identical twin brother remained unaffected, suggesting selective vulnerability despite genetic similarities. The child had a low birth weight (1.82 kg) and required 12 days of NICU stay for respiratory distress. Maternal history included hypothyroidism and Kartagener syndrome. The child’s symptoms emerged at age two, worsening in structured environments. Teachers reported severe distractibility, disruptive behavior, and difficulty completing tasks despite normal cognitive abilities. His identical twin exhibited no symptoms. A family history of mild intellectual disability (IQ 68) in a maternal uncle further suggested a genetic predisposition. Psychiatric examination revealed constant movement, frequent interruptions in conversation, short attention span, and difficulty following commands. Neurological and systemic examination was unremarkable. Based on Scores on the Iowa Conners Rating Scale (>12, suggestive of ADHD) and Malin’s Intelligence Scale for Indian Children (IQ: 102, above average), a diagnosis of ADHD, Combined Presentation was made (ICD 11; 6A05.2). Management involved psychoeducation, pharmacotherapy, environmental modification, and school-based interventions. Methylphenidate (OROS formulation) was initiated with dose titration based on clinical response. School-based interventions included preferential seating, structured routines, shorter task durations, and frequent breaks. Dietary modifications, such as reducing artificial additives and supplementing omega-3 fatty acids (300–600 mg/day), were recommended.[2] After three months, significant improvements were observed in attention span, impulsivity, task completion, and social interactions. Teachers noted fewer classroom disruptions and increased engagement. Parents reported reduced hyperactivity and better adherence to routines, highlighting the effectiveness of multimodal ADHD management.
Preterm birth and low birth weight increase ADHD risk by 1.5 to 2.4 times, likely due to altered cortical development and dopamine dysregulation.[3] Maternal hypothyroidism doubles to triples ADHD risk by impairing fetal neurodevelopment.[4] While IVF is not definitively linked to ADHD, some studies suggest higher neurodevelopmental risks due to placental insufficiency or epigenetic modifications.[5] A unique aspect of this case is the unexplored link between maternal Kartagener syndrome and ADHD. Kartagener syndrome, an autosomal recessive ciliopathy, has not been widely studied in neurodevelopmental disorders. However, emerging evidence suggests that cilia play a crucial role in early neurogenesis, neuronal migration, and synaptic signaling.[6] Further research is needed to investigate whether ciliary dysfunction could contribute to neurodevelopmental disorders like ADHD.
This case underscores the complex interplay of genetics, perinatal insults, and epigenetics in ADHD, highlighting why one twin was affected while the other remained unaffected. The discordance may result from placental function differences, fetal oxygenation variations, or distinct epigenetic modifications in neurotransmitter pathways. Advances in genetic and neuroimaging research could lead to personalized interventions for high-risk children. Further studies should explore long-term neurodevelopmental outcomes in IVF-conceived children and the role of ciliopathies in ADHD pathogenesis.
Authors’ contributions
Literature review and initial drafting: MN; Editing the article: SS, VSC, SP.
Conflicts of interest
There are no conflicts of interest.
Declaration of parents’ consent
The authors certify that they have obtained all appropriate patient’s parents’ consent forms. In the form, the patient’s parents have given their consent for his images and other clinical information to be reported in the journal. The patient’s parents understand that their child’s name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.
Funding Statement
Nil.
REFERENCES
- 1.Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry. 2019;24:562–75. doi: 10.1038/s41380-018-0070-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Bloch MH, Mulqueen J. Nutritional supplements for the treatment of ADHD. Child Adolesc Psychiatr Clin N Am. 2014;23:883–97. doi: 10.1016/j.chc.2014.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.James SN, Rommel AS, Cheung C, McLoughlin G, Brandeis D, Banaschewski T, et al. Association of preterm birth with ADHD-like cognitive impairments and additional subtle impairments in attention and arousal malleability. Psychol Med. 2018;48:1484–93. doi: 10.1017/S0033291717002963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Peltier MR, Fassett MJ, Chiu VY, Getahun D. Maternal hypothyroidism increases the risk of attention-deficit hyperactivity disorder in the offspring. Am J Perinatol. 2021;38:191–201. doi: 10.1055/s-0040-1717073. [DOI] [PubMed] [Google Scholar]
- 5.Sandin S, Nygren KG, Iliadou A, Hultman CM, Reichenberg A. Autism and mental retardation among offspring born after in vitro fertilization. JAMA. 2013;310:75–84. doi: 10.1001/jama.2013.7222. [DOI] [PubMed] [Google Scholar]
- 6.Karalis V, Donovan KE, Sahin M. Primary cilia dysfunction in neurodevelopmental disorders beyond ciliopathies. J Dev Biol. 2022;10:54. doi: 10.3390/jdb10040054. [DOI] [PMC free article] [PubMed] [Google Scholar]
