Mr. X is a 30-year-old male patient, Swiss, Caucasian, from a non-consanguineous union. He is the second child of two siblings. The pregnancy and delivery are said to be unremarkable, with the patient’s development said to be linear during the first three months of life, feeding difficulties with vomiting after bottle-feeding and no notable somatic disorders to be found. The patient subsequently showed a progressive form of overall delay in development associated with autism spectrum disorder, facial dysmorphia, hypotonia, strabismus and behavioral disorders. He therefore joined the children’s sector of a social institution a few days a week and then for school days from the age of five onwards. Medically the patient is known for epilepsy since the age of 18 with notion of generalized tonic-clonic seizures and myoclonic seizures. At the age of 28, Mr. X was hospitalized in a neurological unit for status epilepticus resulting in an increase in his antiepileptic medication.

In the months following this hospitalization, the patient beneficiated from a genetic consultation given his clinical features which associated the various specific signs listed above. Following the genetic analysis, the diagnosis of Bainbridge-Ropers syndrome was made.

Regarding behavioral disorders, he has occasionally presented, since childhood, challenging behaviors, occurring periodically, without any obvious triggers and with spontaneous resolution. During these episodes, he may present with psychomotor agitation, screaming, dropping to the ground, damaging electronic items, or even displaying hetero-aggressive gestures (trying to bite or pull hair, scratching, kicking, or punching), or self-harming (forceful vomiting, scratching himself or banging his head against the wall).

Since the age of 28, he would exhibit such behavioral problem at an increasing rate of several times per day. He would also exhibit new problematic behaviors, such as pulling out his toe and fingernails. The patients’ relatives describe a decline in his mood, along with him becoming withdrawn, a refusal to participate in activities, a drop in social interaction and a tendency to doze off during the day. Eating habits fluctuated, with alternating periods of food refusal and minor hyperphagia. His relatives also described episodes of hyperventilation, occurring since childhood but having increased in frequency and intensity over the recent months, particularly during periods of transition. Finally, the patient presented with a long-standing sleeping disorder, waking frequently during the night, and vocalizing in his sleep.

In view of this behavioral deterioration Fluvoxamine 150 mg/d and Risperidone 1 mg/d were introduced, with no clear improvement in symptomatology, leading to the discontinuation of Risperidone replaced by Olanzapine 10 mg/d without any clinical improvement. These are the treatments recommended to treat symptoms of irritability in patients with autism. The introduction of a treatment of proton pump inhibitor (IPP) 40 mg/j with the hypothesis of gastric reflux pain, which might explain certain challenging behaviors (eating disorders, torso laceration, etc.) led to a slight improvement in hetero-aggressive behaviors, but only transiently. Given the significant clinical deterioration over the previous month, with the onset of self-induced injuries, a tramadol-based treatment 200 mg/d was introduced with the hypothesis of dolor, in parallel to Fluvoxamine and Olanzapine, without any clinical improvement.

In view of the severity and frequency of these challenging behaviors over the previous months, he was admitted to a psychiatric crisis unit dedicated to mental disabilities. This was the patient’s first psychiatric hospitalization.

Usual treatment:

Sodium Valproat tablet: 500 mg morning, 500 mg midday, 1000 mg evening

Lacosamide: 100 mg morning, 100 mg evening

Olanzapine: 10 mg/d

Fluvoxamine: 150 mg/d

Tramadol retard: 100 mg morning, 100 mg evening

Esomeprazole: 40 mg/d

Daily: Alprazolam 0.25 mg treatment for behavioral crises in reserve maximum twice a day

On his arrival, Mr. X presented several episodes of hyperventilation per day (with varying contexts: when a caregiver would address him, at the start of meals, during transitions or sometimes without any context), extremity tremors, provoked vomiting, repeated questions (“who is that?”, “what is that?”, “tomorrow”), regular episodes of screaming and refusal of care. These episodes pointed to a manifestation of anxiety. At the same time, the patient presented with self-aggressive behaviors such as lacerations of the torso, pulling of nails, toes, and fingers, or thermal stimulation by putting his hands under very hot water for several minutes at a time. He also presented with phases of agitation during which he would urinate on electrical outlets, spills water on the floor or on electronic equipment, try to set off alarms, or even display hetero-aggressive gestures (grabbing caregivers’ hair, hitting them with feet or hands). On clinical examination, vital parameters were within normal limits (weight: 54 kg; blood pressure: 108/65 mmHg; heart rate: 71 bpm; oxygen saturation: 100%; temperature: 36.2°C). Severe intellectual disability with language delay, autism, facial dysmorphia with prominent forehead, arched eyebrows and serrated teeth, strabismus, generalized hypotonia associated with skeletal malformations: Marfanoid habitus, pectus excavatum and arachnodactyly were noted. The remainder of the clinical examination revealed self-induced nail-biting lesions on left index finger and all toes without any signs of localized infection. No cardiac, pulmonary or abdominal abnormalities were noted. Neurologically, on two occasions the patient presented with clinical manifestations strongly suggestive of epileptic seizures, despite taking his usual treatment as prescribed. Neurological observation and electroencephalogram evaluation subsequently returned to normal, suggesting an uncertain origin for these seizures. Treatment with brivaracetam 100 mg/d was added, with the aim of improving control of epilepsy. In view of the marked deterioration in the patient’s behavior under Brivaracetam (psychomotor agitation with increased insomnia, major aggressiveness towards others and himself, endangerment by repeated urination onto electrical outlets, etc.) and the absence of any clear argument from the neurology specialists for potential benefits, Brivaracetam was quickly withdrawn.

Regarding gastrointestinal symptoms, the patient presented several episodes of induced vomiting at the beginning of his stay, as well as episodes of hyperventilation before meals, possibly compatible with digestive discomfort. An abdominal scanner and oeso-gastro-duodenal transit were performed in addition to an extensive laboratory work-up. Imagery examens were in the norm. Biological tests showed no obvious abnormalities.

Faced with these clinical features, and in particular the atypical self-aggressive gestures directed at his fingernail, we elaborated on the hypothesis of pain linked to an inflammatory disease of the extremities, as part of the Bainbridge-Ropers syndrome. Treatment with non-steroidal anti-inflammatory (AINS) ex officio (Ibuprofen 200 mg three times a day) was started with improvement in self-harm behaviors during three days, but with no noticeable effect on other symptoms of agitation.

To reduce the risk of iatrogenicity, Tramadol and Fluvoxamine treatments were reduced and then stopped, in view of their lack of effectiveness on behavior when they were first introduced. The Olanzapine treatment was also reduced, then replaced by a low-dose Risperidone treatment (0.5 mg/d).

Due to the rarity of the syndrome, there is currently insufficient knowledge to propose recommendations for the specific management of patients with BRS, apart from proposing a multidisciplinary approach focused on the difficulties presented by the patient. This situation can lead to over-medicalization of patients, with a high risk of iatrogenicity associated with the multiplication of drug treatments. The clinical situation of Mr. X and the treatment with pregabalin, which allowed the almost complete cessation of all other psychiatric treatments, seem to us to be important to highlight in order to propose a therapeutic approach to this rare genetic syndrome.

The introduction of pregabalin in this particular case of a patient with SBR and autism has led to a clear and lasting clinical stabilization. Whether this is a central effect or a pleiotropic effect on a set of syndrome-related manifestations, the question remains unanswered. However, the value of this treatment remains to be assessed for patients with BRS and autism, with the aim of providing specific, individualized care to meet the needs of these patients.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Written informed consent was obtained from the individual's legal guardian/next of kin for the publication of this case report.

MG: Writing – original draft, Investigation, Methodology. JG: Supervision, Writing – review & editing, Validation. VG: Supervision, Validation, Writing – review & editing, Investigation, Project administration.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Open access funding by University of Lausanne.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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