Psychiatric presentation of a child with a COL4A1-related multisystem disorder

Introduction

HANAC syndrome is a rare multisystem disorder caused by pathogenic COL4A1 variants and may involve cerebral vessels, kidneys, eyes, and muscles [1]. Pediatric literature has mainly focused on stroke, porencephaly, epilepsy, and developmental abnormalities. More recently, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and other neurodevelopmental disorders have also been reported in some patients [2]. We report an 8-year-old boy with HANAC syndrome whose childhood psychiatric presentation was characterised by prominent obsessive-compulsive symptoms, ADHD, and tic phenomena, a combination rarely described in the literature.

Case Presentation

An 8-year-old boy was referred to child and adolescent psychiatry because of obsessive-compulsive symptoms, hyperactivity, elimination problems, and motor/vocal tics. Developmental history revealed longstanding hyperactivity, delayed toilet training, age-appropriate early motor milestones, and mild speech/articulation difficulties. Formal cognitive assessment showed average intellectual functioning (WISC-R Full Scale IQ: 103).

Genetic testing identified a heterozygous pathogenic COL4A1 variant. Medical history also included recurrent episodes of muscle pain/cramps with creatine kinase elevations above 1000 IU/L, hypertension treated with amlodipine, and nephrology follow-up, consistent with his established diagnosis of HANAC syndrome. Available investigations, including EEG and fundus examination, were unremarkable, whereas psychiatric symptoms represented the predominant source of functional impairment.

Psychiatric evaluation revealed clinically significant obsessive-compulsive symptoms, including contamination-related avoidance behaviours (refusal to walk barefoot on tiled surfaces or share drinking vessels), refusal to use utensils after contact with surfaces, symmetrical touching compulsions after touching objects with one hand, and “just-right” phenomena. These symptoms were associated with pronounced rigidity, family distress, and impairment in daily functioning.

He also had inattentive and hyperactive symptoms impairing school functioning, together with fluctuating motor/vocal tics. Tics included eye blinking, throat clearing, repetitive sounds, and recurrent facial movements. Daytime urinary incontinence and intermittent faecal incontinence were also present. DSM-5 diagnoses were obsessive-compulsive disorder, attention-deficit/hyperactivity disorder (combined presentation), Tourette’s disorder, enuresis (diurnal subtype), and encopresis.

Treatment included fluoxetine targeting obsessive-compulsive symptoms, low-dose aripiprazole for tic symptoms, and methylphenidate for ADHD symptoms, together with family-based and elimination-focused behavioural interventions. Obsessive-compulsive symptoms were addressed using CBT-informed bibliotherapy with What to Do When Your Brain Gets Stuck: A Kid’s Guide to Overcoming OCD; symptoms were externalised and named “Batman” by the child [3]. This facilitated engagement and exposure-based work. During follow-up, obsessive-compulsive symptoms markedly improved, faecal incontinence substantially decreased, urinary accidents were reduced, and academic functioning improved after stimulant optimisation. Baseline Clinical Global Impression–Severity (CGI-S) scores were estimated as 5 (markedly ill) for OCD and ADHD symptoms. Clinical Global Impression–Improvement (CGI-I) ratings at last follow-up were 1 (very much improved) for OCD, 2 (much improved) for ADHD and elimination disorders, and 3 (minimally improved) for tics.

Conclusions

This case suggests that psychiatric symptoms may represent an important source of functional impairment in some children with HANAC syndrome. Structured psychiatric assessment may help identify treatable obsessive-compulsive, attentional, tic, and elimination-related symptoms. Multidisciplinary collaboration between psychiatry, genetics, paediatrics, and nephrology may be beneficial in complex presentations of this kind. Early psychiatric involvement may improve functional outcomes. Further reports are needed to better characterise psychiatric manifestations in HANAC syndrome.

References

1. Plaisier, E., Gribouval, O., Alamowitch, S., et al., 2007. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms and muscle cramps. N. Engl. J. Med. 357 (26), 2687-2695.
2. Ozlu, C., et al., 2024. COL4A1/COL4A2 variants in 16 pediatric patients: stroke, porencephaly, schizencephaly and related findings. Pediatr. Stroke J. 9, 29-75.
3. Huebner, D., 2007. What to Do When Your Brain Gets Stuck: A Kid’s Guide to Overcoming OCD. Magination Press, Washington, DC.