Body-Focused Repetitive Behaviors in Patients with FOXP1 Syndrome: An International Cross-Sectional Survey-Based Study

FOXP1 syndrome is a rare neurodevelopmental disorder due to forkhead box protein 1 (FOXP1) gene mutations and is associated with intellectual disability, dysmorphic features, and autism spectrum disorder (ASD) [1]. Siper et al. [1] reported compulsive skin and nail picking in 56% of FOXP1 syndrome patients in a small prospective phenotype characterization study (n = 9). Therefore, we aimed to assess body-focused repetitive behavior (BFRB) prevalence in this patient population using a cross-sectional survey-based study.

A validated survey [2] assessing for BFRBs was administered to parents attending the International FOXP1 Foundation conference on June 21, 2023, with a 76.7% (33/43) response rate. A digital survey was sent to the International FOXP1 Foundation listserv, with 37 responses (unknown denominator). The International FOXP1 Foundation is a support group for FOXP1 syndrome patients and their families. Inclusion criteria were patients with a genetically confirmed diagnosis of FOXP1 syndrome as self-reported by parents. BFRB severity was calculated individually for each BFRB scale based on three domains (time spent, interference, and distress).

A total of 70 surveys were completed, with an average participant age of 10.9 years (range: 1–37). The majority (85.7%) had ≥1 psychiatric comorbidity, most commonly ASD (54.3%) and attention-deficit hyperactivity disorder (47.1%) (Table 1). Excoriation disorder, onychophagia, onychotillomania, and trichotillomania were reported by 58.6%, 38.6%, 29.7%, and 10.0% of subjects, with 63.4%, 59.3%, 54.5%, and 14.3% having moderate to severe disease, respectively (online suppl. Table 1, 2; for all online suppl. material, see https://doi.org/10.1159/000537906; Fig. 1, 2). Overall, 28.6%, 30.0%, and 10.0% had one, two, and three BFRBs, respectively.

Sequelae were reported by 83.3% (40/48) of patients, most commonly bleeding (50.6%), scarring (21.2%), and infection (15.2%). Most patients (70.0%) reported other repetitive behaviors, including picking and pulling other people’s skin and hair, respectively.

Overall, 77.1% and 81.3% of patients and patient families, respectively, reported BFRB-associated distress (online suppl. Table 3). On average, patients reported having BFRBs for 6.8 years, with 79.1% reporting stable or worsening disease course. Only 22.9% of patients saw a physician for their BFRB, and of those, 37.5% reported satisfaction with treatment (online suppl. Table 4).

We demonstrate strikingly high BFRB prevalence in FOXP1 syndrome patients surveyed compared to the general population, which is estimated at 1.2–11.2% for excoriation disorder [3], 20–45% for onychophagia [4], 0.9% for onychotillomania [4], and 0.6–2.9% for trichotillomania [3]. In a meta-analysis [5] of 14,379 patients with ASD, pooled prevalence of self-injurious behavior was 42%, with hair pulling and self-scratching associated with intellectual disability (p = 0.008, p = 0.002, respectively), which may explain why FOXP1 syndrome patients, many of whom have both ASD and intellectual disability, are at increased BFRB risk. Stimulus control (reducing BFRB cues such as idleness), aversion therapy (pairing BFRB with discomfort, such as applying unpleasant-tasting nail polish to discourage onychophagia), habit reversal training (teaching alternative behaviors such as fist clenching or sitting on hands), or pharmacotherapies (such as N-acetylcysteine or antidepressants) are potential BFRB treatments for FOXP1 syndrome patients [4, 6].

Cutaneous infections were frequently self-reported with BFRBs in our survey-based study. Similarly, Siper et al. [1] reported a recurrent skin infection rate of 22% in FOXP1 syndrome patients. Cutaneous infections may be BRFB-associated complications, or FOXP1 patients may have higher infection risk, given the potential role of FOXP1 in immune regulation.

Estimated prevalence of FOXP1 syndrome is <1/1,000,000, with only ∼200 patients identified to date. Therefore, while sample size is small, the study includes a large proportion of patients. Volunteering bias and survey design are limitations.

In conclusion, we show that prevalence of BFRBs is dramatically high among FOXP1 syndrome patients surveyed, affecting quality of life for patients and their families and causing significant sequelae. Dermatologists are well positioned to advocate for FOXP1 syndrome patients and to manage BFRBs as part of a multidisciplinary approach.

This study was reviewed and approved by the Medical Ethical Review Committee of Weill Cornell Medicine (IRB #23-05026040). The study has been granted an exemption from requiring written informed consent by the medical ethical review committee of Weill Cornell Medicine. Informed consent was obtained for publication of accompanying figures.

The authors have no conflicts of interest relevant to the content of this article.

No specific funding was received from any bodies in the public, commercial, or not-for-profit sectors to carry out the work described in this article.

Kaya L. Curtis prepared methodology, acquired and interpreted data for the work, wrote the original manuscript draft, prepared tables, gave final consent for the version to be published, and agreed to be accountable for all aspects of the work. Dr. Shari R. Lipner conceptualized the work, prepared methodology, acquired and interpreted data for the work, reviewed and edited the manuscript, gave final consent for the version to be published, and agreed to be accountable for all aspects of the work.

The authors confirm that the data supporting the findings of this study are available within the article. Further inquiries can be directed to the corresponding author.