The Psychiatric Manifestations of Sturge Weber Syndrome: A Scoping Review

Sturge-Weber syndrome is a neurocutaneous syndrome of the brain, skin, and eye characterized by leptomeningeal venous malformation (abnormal growth of blood vessels) and a facial port-wine stain birthmark in the distribution of first division of the trigeminal nerve (CN V1). ¹ It is estimated to affect 3.08 per 100 000 people per year, although comprehensive population-based data on prevalence are limited.^2,3 First characterized clinically by William Allen Sturge in 1879, pathologically by Kalischer in 1901, and radiologically by Weber in 1922, the condition was formally named in 1935 by Professor Hilding Bergstrand in honor of 2 of its early researchers. ¹ In 2014, Shirley et al ⁴ discovered a somatic mosaic mutation in GNAQ as a major genetic cause of vascular disruption in Sturge-Weber syndrome (earlier progenitor mutation) and port-wine stains (later progenitor mutation).

Sturge-Weber syndrome is most commonly associated with a p.Arg183Gln somatic mutation in the gene GNAQ. ⁴ This mutation prevents the protein Gαq from returning to its inactive state, causing hyperactivation of downstream signaling pathways and abnormal blood vessel development. ⁴ Further research has also suggested a possible role for other mutations in genes such as GNA11 in the pathogenesis of Sturge-Weber syndrome. ⁵ Cortical malformations likely occur as a result of abnormal venous drainage and ischemia, with seizures increasing the metabolic needs of brain tissue and worsening the venous ischemia, potentially leading to strokelike episodes and subsequent neurologic deficits.^1,2,6 Such ideas are supported by reports of improvements in neurologic symptoms after starting aspirin. ⁷ In addition to abnormal blood vessel development, aberrant innervation has been linked to Sturge-Weber syndrome pathophysiology, with Cunha e Sá et al ⁸ reporting a lack of normal cholinergic and sensory fibers innervating abnormal cortical vessels in Sturge-Weber syndrome.

Sturge-Weber syndrome can be classified into 3 types: type I is characterized by a facial port-wine stain and brain involvement (leptomeningeal venous malformation) and is the most common type; type II is characterized by a facial port-wine stain but no brain involvement; type III is characterized by only brain involvement (no facial birthmark). ¹ Often presenting and progressing during early childhood, Sturge-Weber syndrome has a variable clinical presentation, including seizures, hemiparesis, glaucoma, headaches, and neurologic and cognitive delays. ¹ Seizures occur in nearly all Sturge-Weber syndrome patients and often begin within the first 2 years of life.^1,9,10 In addition to seizures, intellectual and cognitive delays are among the most common clinical characteristics of Sturge-Weber syndrome, estimated to affect more than 50% of Sturge-Weber syndrome individuals. ⁹

Sturge-Weber syndrome diagnosis is suspected in all cases of facial port-wine stain. ¹ Structural neuroimaging using T1-weighted magnetic resonance imaging (MRI) with gadolinium contrast as well as susceptibility-weighted imaging (SWI) can be used to identify classical radiologic characteristics of Sturge-Weber syndrome, such as asymmetric abnormal venous drainage and pial contrast enhancement, indicating leptomeningeal angiomatosis, in patients.^11,12 Interestingly, a recent paper by Juhász et al ¹³ reports that noncontrast, nonsedated MRI is a feasible alternative to traditional contrast-enhanced MRI under sedation for Sturge-Weber syndrome diagnosis, even in children with cognitive and behavioral issues, representing advances in the area of imaging for Sturge-Weber syndrome patients. As the disease progresses, dilation of the choroid plexus as well as cortical atrophy and calcification may occur and appear in imaging as well.^11,12 In addition to structural neuroimaging, functional imaging using fluorodeoxyglucose positron emission tomography (FDG-PET) can also be helpful in identifying regions of the brain characterized by hypometabolism, which may indicate association with epilepsy and is a poor prognostic indicator.^1,14

Seizures in patients with Sturge-Weber syndrome are treated with anticonvulsant medications, low-dose aspirin, and surgery (eg, hemispherectomy) for more severe, refractory cases. ¹⁵ Laser therapy is often performed to lighten the facial port-wine stain, and abortive/preventive/pain medications can help with migraines.^1,2 Because of the high prevalence and late onset of glaucoma among Sturge-Weber syndrome patients, ophthalmologic observation with annual examinations and intraocular pressure monitoring is recommended throughout patients’ lives.^1,2

Although many clinical characteristics of Sturge-Weber syndrome, such as seizures and glaucoma, have been well-characterized in the literature, psychiatric manifestations remain insufficiently studied and lack comprehensive analysis. This review aims to address this gap by examining existing literature on psychiatric symptoms and disorders observed in individuals with Sturge-Weber syndrome.

Methods

We searched the PubMed, Scopus, and Embase databases on September 1, 2024, using the following search terms: PubMed: sturge weber[Title], Scopus: TITLE (sturge AND weber), Embase: ‘sturge weber syndrome’:ti. This search resulted in 1923 papers available in English, after duplicates were identified and removed. Titles, abstracts, and/or full texts were initially screened by the authors (VL and RRG). Studies were included if they made any mention of behavioral or psychiatric symptoms. This yielded 81 papers, for which two authors (VL, RRG) independently reviewed the full texts for relevance. Review articles were excluded. We did not impose restrictions on date. We also examined the bibliographies of relevant studies and review articles, yielding an additional 5 papers to include in this review. Overall, this yielded 36 papers, from which data were extracted by 2 authors (VL, RRG). We included studies that reported data on behavioral or psychiatric symptoms in individuals with any type of Sturge-Weber syndrome. See Figure 1 for a flow diagram illustrating our search.

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Figure 1.

Flow chart showing process of selection for articles included in this review.

Results

Several studies have reported on psychiatric symptoms in individuals with Sturge-Weber syndrome, examining their prevalence, associated comorbidities, contributing factors, and treatment options.

In a study by Day and colleagues, researchers examined the impact of physical and genetic factors on symptoms in 277 people (2 months–66 years old) with Sturge-Weber syndrome and brain involvement based on contrast-enhanced MRI. The investigators reported that, among all subjects, attention-deficit hyperactivity disorder (ADHD) was present in 14.1% of individuals, a behavioral disorder in 10.8% of individuals, a mood disorder in 7.6% of individuals, and an autism spectrum disorder in 2.9% of individuals (23.8%, 17.7%, 13.6%, and 4.8%, respectively, in individuals aged >6 years). A family history of psychiatric disease was associated with the presence of mood disorders, and a family history of ADHD/ADD was associated with the presence of ADHD/ADD in all patients, whereas those with a family history of psychiatric disease was associated with both mood and behavioral disorders in individuals aged >6 years. A family history of ADHD was also associated with ADHD in individuals aged >6 years. Neither uni- nor bilateral brain disease nor age of seizure onset distinguished between the presence of any psychiatric condition. ¹⁶

In another study, Chapieski et al ¹⁷ examined emotional characteristics of 79 young people with Sturge-Weber syndrome (between 4 and 18 years old) in comparison to 52 of their similarly aged siblings based on questionnaires sent to their parents and teachers. The investigators reported that young people with Sturge-Weber syndrome have significantly greater depression, but not anxiety or withdrawn behavior, compared with their siblings according to parents, as well as higher levels of behaviors associated with oppositional defiant disorder and conduct disorder according to teachers. The presence of a seizure disorder was significantly associated with depression and behaviors associated with ADHD and oppositional defiant disorder, whereas the size of the port-wine stain was significantly associated with the presence of depression in individuals aged >9 years.

Sujanksy et al ¹⁸ also sought to investigate emotional and behavioral issues in 27 adults with Sturge-Weber syndrome via chart review, questionnaires, and telephone interviews. Of 12 individuals with normal intellectual functioning, depression was reported in 6 individuals and “emotional outbursts” in 1. Of the other 15 individuals, 5 had depression, aggressive or “noncompliant” behavior was reported in 6, self-harming behavior in 1, and hyperactivity in 1, whereas 2 could not be fully assessed.

In their study, Turin et al ¹⁹ examined psychiatric symptoms and diagnoses in 16 patients with Sturge-Weber syndrome (between the ages of 3 and 34 years) using psychiatric interviews of patients, questionnaires, and MRI reports. The investigators reported a trend-level association between a diagnosis of disruptive behavior disorder not otherwise specified and having seizures in the previous 3 months. Problems with mood were reported in 94% of individuals, learning in 78%, attention in 71%, and sleep in 57%. Oppositionality was reported in 5 of 10 youths and 1 of 6 adults. Physical aggression was reported in 6 of 10 youths and no adults. Anxiety was reported in 4 of 10 youths and no adults. Formal Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnoses of a mood disorder were made in 31%, a disruptive behavior disorder in 25%, adjustment disorder in 25%, learning disorder in 6%, and pervasive developmental disorder not otherwise specified in 6%.

In addition to larger studies, several case reports detail psychiatric symptoms, especially depression, in Sturge-Weber syndrome patients. For example, Mamidipalli et al ²⁰ published a case report describing an 18-year-old male patient with type II Sturge-Weber syndrome with no cognitive or developmental delays who presented with depression in the context of bipolar affective disorder and responded to sodium valproate. In another case report by Gadit, ²¹ a 22-year-old male patient with Sturge-Weber syndrome presented with behavioral issues, social withdrawal, and self-harming tendencies as well as evidence of depression and anxiety at age 17 years. He was treated with citalopram, clonazepam, thyroxine (patient had hypothyroidism), and lamotrigine (patient had a seizure disorder), which somewhat improved his depression and anxiety. ²¹ A third case report, written by Kapadia et al, ²² describes a 38-year-old married female with Sturge-Weber syndrome and a severe and progressive pain syndrome who also experienced high levels of depression and anxiety. Similarly, Lee describes a 19-year-old single female with substantial developmental delay who presented with depression, self-mutilation, posturing, food refusal, and incontinence.^23,24 Her symptoms improved to some degree with amitriptyline and psychosocial treatments.^23,24 In a more mild case, Jancar reports on a 67-year-old male with Sturge-Weber syndrome who was described as being “very moody.” ²⁵

Overall, mood disorders, especially depression, appear to be relatively commonly observed among individuals with Sturge-Weber syndrome. These findings suggest that individuals with Sturge-Weber syndrome may also be at higher risk of self-harming and suicidal behaviors. Sebold and colleagues screened 34 patients with Sturge-Weber syndrome (between the ages of 8 and 47 years) and compared them to other neurology patients. Six of the Sturge-Weber syndrome patients screened positive for suicide risk. Use of selective serotonin reuptake inhibitors (SSRIs) among patients with Sturge-Weber was also associated with increased suicide risk. A diagnosis of Sturge-Weber syndrome conferred a greater suicide risk compared with having another neurologic condition. Three of the 6 individuals with Sturge-Weber syndrome who screened positive for suicide risk were taking SSRIs, whereas only 2 of the 28 individuals with Sturge-Weber syndrome who did not screen positive for suicide risk were taking SSRIs. ²⁶

Although there are no larger studies that report on psychotic symptoms in Sturge-Weber syndrome patients, there are several case reports that describe this phenomenon. A case report by Nkemjika et al ²⁷ describes a 30-year-old male with Sturge-Weber syndrome and an associated seizure disorder who presented to the emergency department with agitation and aggression toward family members, persecutory delusions related to family members, and auditory hallucinations that he had been experiencing for more than a year. He was admitted to the inpatient psychiatric unit, diagnosed with schizophrenia, and treated with olanzapine and phenytoin (for seizures), leading to improvement. ²⁷ In another case report, Kalaitzi et al ²⁸ describe a 33-year-old man with Sturge-Weber syndrome who presented with 10 days of psychomotor agitation and persecutory delusions. He was diagnosed with brief psychotic disorder and prescribed weekly penfluridol, which led to a resolution of his symptoms. ²⁸ They returned after 3 months and responded to an increase in his dose of penfluridol. ²⁸ Similarly, in their case report, Calzada et al ²⁹ describe a 45-year-old man with Sturge-Weber syndrome who presented with persecutory delusions that improved with amisulpride and antiepileptic medications. Lee ²³ describes an 18-year-old single man with a family history of schizophrenia (mother) who presented with persecutory delusions for 1 week. He improved with psychotherapy and medications, which were discontinued on discharge, though he was socially reclusive. ²³ He eventually developed obsessive-compulsive disorder and partially responded to fluoxetine and supportive psychotherapy. ²³ In the same report, the authors describe a 35-year-old man who had been hospitalized at a psychiatric hospital for the previous 16 years and treated with antipsychotic medications because of severe aggression and paranoia. ²³ A report by Chen et al ³⁰ describes a 33-year-old female with Sturge-Weber syndrome who began experiencing persecutory delusions at age 24 years and auditory hallucinations at age 28 years. She attempted suicide at age 31 years and ultimately responded to risperidone. ³⁰ The authors suggested a potential relationship between the development of psychotic symptoms and progressive pathology of the left temporal/frontal lobes in Sturge-Weber syndrome patients. ³⁰ In their report, Mankar et al ³¹ describe a 32-year-old female with Sturge-Weber syndrome and associated mild developmental delay and seizures, who presented with incoherent speech, inappropriate “smiling and muttering to self,” irritability, sleep disruption, and social withdrawal for 3 months. She was treated successfully with risperidone, valproate, phenobarbitone, and ivermectin. ³¹ In another case report, Rimon et al ³² describe a 15-year-old female with Sturge-Weber syndrome and a history of seizures who presented with paranoia, erotomanic delusions, and auditory hallucinations that were treated successfully with anticonvulsive and antipsychotic medication.

A study by Saraf et al ³³ describes a unique case of postpartum psychosis in a 45-year-old woman with Sturge-Weber syndrome and a history of childhood seizures. She presented with recurrent persecutory and referential delusions, auditory hallucinations, aggression, and altered sleep that began 1 day postpartum. Her symptoms remitted after a month of treatment with olanzapine. ³³

In addition to these studies, other articles investigate questions regarding comorbidities associated with psychiatric symptoms in Sturge-Weber syndrome patients. For example, in their study of 55 individuals with Sturge-Weber syndrome, epilepsy, and headaches, Kossoff et al ³⁴ observed that 56% reported a mood disturbance. In their study, Harmon et al ³⁵ examined 22 individuals (8-17 years old) with Sturge-Weber syndrome and brain involvement based on contrast-enhanced MRI and found that antidepressant use was associated with lower cognitive function (though not after depression was taken into account), earlier age at seizure onset, and greater extent of glaucoma, but not skin and brain involvement. The authors also reported that depression was inversely correlated with cognitive function. ³⁵

This relationship between epilepsy and psychiatric symptoms is also highlighted in a case report by Mirsepassi et al ³⁶ that describes a 45-year-old man with a history of seizures with visual aura (controlled with carbamazepine and phenytoin), developmental delays, behavioral issues, and a suicide attempt at age 25, who presented with symptoms of mania and aggression. These were partly attributed to complex partial seizures with psychic aura and were treated successfully with an increase in his dose of carbamazepine. ³⁶ Another case report that depicts psychiatric symptoms attributed to seizure activity is by Madaan et al, ³⁷ who describe an 82-year-old man with Sturge-Weber syndrome and a history of seizures. He presented to the hospital from a retirement community after an episode in which he smelled smoke that was not present and then slapped a nurse who came to check on the situation. These were attributed to complex partial seizures and treated with risperidone and an increased dose of lamotrigine.

Specifically focusing on behavioral challenges in patients with Sturge-Weber syndrome, several studies highlight the prevalence of ADHD and related behavioral issues. Pascual-Castroviejo et al ⁹ reported that 42% of 55 patients with Sturge-Weber syndrome had emotional or behavioral issues consistent with ADHD. Similarly, Brunklaus ³⁸ reported on a review of charts from 92 children with Sturge-Weber syndrome and found behavioral difficulties in 50%, emotional distress in 44%, and hyperactive inattention in 53%. In addition, they found that sleep and behavioral issues were closely linked, and both were unrelated to seizure frequency or a history of status epilepticus. In another study, Raches ³⁹ examined 20 children with Sturge-Weber syndrome and seizures, and 14 without seizures, all between the ages of 8 and 13 years, using questionnaires filled out by parents and teachers. Teachers reported that individuals with Sturge-Weber syndrome and seizures engaged in more disruptive behavior (specifically conduct problems, inattention, and oppositional behavior, motor hyperactivity) than individuals with Sturge-Weber syndrome without seizures.

Two case reports also explore ADHD and related behavioral issues in individuals with Sturge-Weber syndrome. In the first report, a 14-year-old female patient presented with oppositional-defiant-type behaviors. ⁴⁰ In the second report, Zabel et al ⁴¹ describe a 9-year-old male patient with anxiety and issues with attention and behavioral dyscontrol, as well as an 8-year-old male patient with problems with attention and impulsivity.

Sleep disturbances also represent a significant concern for patients with Sturge-Weber syndrome. In a study by Saini et al, ⁴² 10 of 12 children with Sturge-Weber syndrome were found to have significant sleep difficulties based on the Children's Sleep Habits Questionnaire–Revised.

To investigate the treatment of psychiatric symptoms in Sturge-Weber syndrome patients, Sebold et al ⁴³ investigated the use of oral sirolimus for 6 months in 10 young patients (ages 5-20 years) with Sturge-Weber syndrome and cognitive impairment. The treatment significantly improved processing speed, anger, and depression (the latter two measured by a neurologic quality of life scale).

Similarly, Kaplan et al ⁴⁴ investigated the use of cannabidiol in 5 patients (ages 2-19 years) with Sturge-Weber syndrome and treatment-resistant epilepsy. Although some patients reported improved mood and behavior, 2 individuals experienced behavioral issues. ⁴⁴ Smegal et al ⁴⁵ conducted an open-label clinical trial of 6 months of oral cannabidiol to assess its use in 10 patients (ages 3-34 years) with Sturge-Weber syndrome, brain involvement, controlled seizures, and cognitive impairment. Among 9 of the patients at baseline, 5 had ADHD, 3 had generalized anxiety disorder, 3 had an unspecified depressive disorder, 2 had separation anxiety disorder, 2 had social anxiety disorder, 1 had panic disorder, and 1 had a major depressive episode. ⁴⁵ The study found anxiety, depression, and somatization all improved during the course of treatment. ⁴⁵

In a retrospective chart review, Lance et al ⁴⁶ examined 12 patients with Sturge-Weber syndrome and brain involvement who were taking a stimulant medication (11 for ADHD, 1 for alertness). They found that stimulants were started at an average age of 10.5 years and taken for an average of 24.5 months. Eight of the patients reported side effects, primarily appetite suppression and headaches, and all but 1 of the patients reported the stimulant medication to be efficacious. Although 1 patient experienced a seizure while taking their stimulant medication, seizure scores remained stable in most patients.

In addition to pharmacologic interventions, 2 case reports describe the use of hemispherectomy in patients with Sturge-Weber syndrome. In the first report, Melim et al ⁴⁷ describe a 22-year-old male patient with Sturge-Weber syndrome who underwent left hemispherectomy at age 1 year to treat refractory seizures. At the age of 19 years he developed severe behavioral problems, which were treated with medications as well as admission to a specialized institution for rare diseases. According to the report, he has since “experienced a calm and functional life,” though it is unclear what role the hemispherectomy played in his initial behavior or its improvement. In a second case report, Falconer et al ⁴⁸ describe 3 patients in which hemispherectomy significantly improved behavioral dyscontrol: a 6-year-old girl who underwent left-sided hemispherectomy, a 3.5-year-old girl who underwent a right-sided hemispherectomy, and a 16-year-old boy who underwent a left-sided hemispherectomy.

In addition to mood disorders, psychotic symptoms, and behavioral issues, 2 studies specifically focused on the presence of autism spectrum disorder (ASD) and/or social/behavioral difficulties in patients with Sturge-Weber syndrome. Gittens et al ⁴⁹ found that within their cohort of 92 children (2-19 years old) with Sturge-Weber syndrome, ASD was present in 24% of individuals, social communication difficulties in 45%, ADHD in 5%, and behavioral difficulties in 50%. Individuals with ASD had lower IQ (intelligence), DQ (development), and total language composite scores compared with the rest of the cohort. Although ASD was more commonly seen in children with bilateral angioma, there was no association between ASD and epilepsy. ⁴⁹ In a second study of 124 young people with Sturge-Weber syndrome (ages 2-19 years), Sloneem et al ⁵⁰ reported that 32% of their cohort was diagnosed with autism, with a diagnosis of autism significantly associated with being older and undergoing epilepsy surgery. In addition, this study found that many children without a diagnosis of autism had moderate to severe social communication impairments.

Finally, Newson-Davis and colleagues examined the transition from pediatric to adult health care services for 20 young people with Sturge-Weber syndrome (between ages 12 and 22 years) using a questionnaire filled out by patients and/or their families. ⁵¹ Many reported little guidance or assistance in making this transition as well as inadequate support for specific challenges such as anxiety, socializing, and living independently, highlighting the need for a more robust health care plan for young people with Sturge-Weber syndrome transitioning to adulthood (Table 1).

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Table 1.

Case Reports of Sturge-Weber Syndrome and Psychiatric Symptoms.

Author	Year	Age, y	Sex	Psychiatric symptom(s)
Mamidipalli 20	2021	18	M	Depression (within the context of bipolar disorder)
Gadit 21	2011	22	M	Depression, anxiety, behavioral issues, social withdrawal, self-harming
Kapadia 22	2012	38	F	Depression, anxiety
Mirsepassi 36	2016	45	M	Mania, aggression, suicide attempt
Nkemjika 27	2023	30	M	Agitation, aggression, persecutory delusions, auditory hallucinations. Diagnosed with schizophrenia.
Kalaitzi 28	2005	33	M	Psychomotor agitation, persecutory delusions. Diagnosed with brief psychotic disorder
Lee23,24	1990, 1992	18	M	Persecutory delusions, followed by obsessive-compulsive disorder (OCD)
		35	M	Severe aggression and paranoia
		19	F	Depression, self-mutilation, posturing, food refusal, incontinence
Jancar 25	1975	67	M	Problems with mood
Madaan 37	2006	82	M	Olfactory hallucinations, aggression.
Mankar 31	2019	32	F	Incoherent speech, inappropriate “smiling and muttering to self,” irritability, sleep disruption, and social withdrawal
Rimon 32	2018	15	F	Paranoia, erotomanic delusions, auditory hallucinations
Calzada 29	2020	45	M	Persecutory delusions
Saraf 33	2019	45	F	Recurrent persecutory and referential delusions, auditory hallucinations, aggression, and altered sleep. Diagnosed with postpartum psychosis.
Chen 30	2006	33	F	Persecutory delusions, auditory hallucinations, suicide attempt
Hrnchiar 40	1963	14	F	Oppositional-defiant-type behaviors
Zabel 41	2010	9	M	Anxiety and issues with attention and behavioral dyscontrol
		8	M	Problems with attention and impulsivity
Melim 47	2020	22	M	Severe behavioral problems
Falconer 48	1960	6	F	Severe behavioral dyscontrol
		3.5	F	Severe behavioral dyscontrol
		16	M	Severe behavioral dyscontrol

Discussion

We reviewed the extant literature on psychiatric and behavioral signs and symptoms associated with Sturge-Weber syndrome. This included 36 research studies and case reports. Overall, we found that the literature on the psychiatric or behavioral manifestations of Sturge-Weber syndrome to be relatively scarce, especially considering how common they are. Further, the reported prevalence of psychiatric and behavioral signs and symptoms associated with Sturge-Weber syndrome varies widely among cohorts. The prevalence rates of mood disorders and disturbances were reported to be anywhere from the single digits to essentially all examined individuals with Sturge-Weber syndrome, with depressive symptoms being the most commonly reported.^16,18,19 Anxiety was less frequently discussed in the literature, with Turin et al ¹⁹ reporting anxiety in 40% of their youth cohort (none of which qualified for a formal DSM diagnosis) and none in their adult cohort. ADHD was reported in between approximately 10% and approximately half of individuals with Sturge-Weber syndrome, although more general issues with behavior, attention, and hyperactivity were frequently noted.^{9,16,18,19,38,39} The prevalence rates of autism spectrum disorders were reported to be anywhere from the low single digits to approximately a third of individuals examined.^16,49 Psychotic symptoms appear to be less commonly reported, primarily in case reports. Behavioral issues and aggression were frequently reported.

Several factors likely contribute to the broad variability in reported rates. First, many of the existing studies have small sample sizes, with only Day et al ¹⁶ and Sloneem et al ⁵⁰ having a cohort of >100 individuals. In addition, many studies rely on questionnaires completed by individuals themselves or by parents and teachers, which introduces variability because of subjective reporting and potential bias. Formal DSM diagnoses are seldom obtained or reported, and structured diagnostic interviews uncommonly conducted, leaving it unclear how many individuals with psychiatric symptoms actually meet diagnostic criteria for a specific psychiatric disorder. For example, studies that conducted psychiatric interviews, such as the one by Turin et al, ¹⁹ reported higher prevalence of psychiatric symptoms and disorders than others that relied more so on questionnaires filled out by family members and others. This suggests that the method of data collection may play a major role in reported prevalence rates, and that many studies may be underestimating the true burden of psychiatric symptoms in Sturge-Weber syndrome patients. Adding to this ambiguity, Gadit comments on the fact that that depression may present differently in Sturge-Weber syndrome patients, often manifesting as “disturbed or aggressive behaviour.” ²¹ This atypical presentation may contribute to the underreporting of depressive symptoms and disorders in individuals with Sturge-Weber syndrome. Additionally, Kanne has noted that diagnostic overshadowing can be a significant issue among individuals with psychiatric conditions, potentially leading to inaccurate reported rates of comorbidity. ⁵² In the future, studies with larger sample sizes and that use structured diagnostic interviews administered by clinician interviewers (rather than self-report) can help to standardize findings and provide a more accurate representation of psychiatric disorder prevalence in Sturge-Weber syndrome patients.

Despite the wide range in reported rates, it is clear that individuals with Sturge-Weber syndrome are at risk for a variety of psychiatric symptoms. Depression was one of the most commonly reported conditions among Sturge-Weber syndrome patients. This elevated rate of depression may contribute to the relatively high suicide risk reported among individuals with Sturge-Weber syndrome. ²⁶ These data underscore the importance of properly identifying and addressing psychiatric symptoms in this population.

The link behind the association between Sturge-Weber syndrome and mood symptoms is likely multifactorial and not yet fully studied. This relationship may, in part, be due to the social and psychological impact of a visible port-wine stain birthmark, or so-called dermatological shame. ²⁰ This is consistent with the findings of Chapieski and colleagues who reported that the size of the port-wine stain was significantly associated with the presence of depression in individuals aged >9 years in their cohort. ¹⁷ In addition, several patients in the Sujansky et al ¹⁸ cohort attributed their depression to poor self-esteem because of the cosmetic appearance of their birthmark. These findings highlight the role that negative cosmetic self-image may play in the development of mood symptoms. In fact, one of the individuals included in the case report by Lee reported being “frequently ridiculed and bullied” by her classmates at school, causing her to “avoid eye contact” with others. ²³ This social isolation and negative self-image may have contributed to the development of her depressive symptoms.

In addition to the consequences of a facial birthmark, other social factors associated with Sturge-Weber syndrome may contribute to mood symptoms, including difficulties and worries about seizure control, vision loss, and intellectual delays. For example, some Sturge-Weber syndrome patients in the Sujansky et al ¹⁸ cohort attributed their depression to frustration with seizure control and headaches. Chapieksi et al ¹⁷ also found a significant association between depression and presence of a seizure disorder, although this relationship (seizure disorder with mood disorder) was not reported in other studies, for example, by Turin et al. ¹⁹ Additionally, Sujansky et al ¹⁸ also reported that many individuals with Sturge-Weber syndrome, because of epileptic disorders or intellectual disabilities, were unable to work in regular employment, be financially self-sufficient, and live independently—factors that likely contribute to heightened levels of depression. More investigation into the neurologic correlates of psychiatric signs and symptoms is warranted.

Genetic factors may also contribute to psychiatric comorbidity in Sturge-Weber syndrome. For example, abnormalities in expression of GNAQ, a major genetic cause of Sturge-Weber syndrome, ⁴ have also been reported in schizophrenia.^53,54 However, based on the case reports discussed herein, there is no clear pattern or association that suggests a pathoetiology to the development of psychosis in Sturge-Weber syndrome, whether family history, ²³ left-sided brain involvement,^30,33 or cannabis. ²⁷

Given the high rates of psychiatric symptoms in Sturge-Weber syndrome patients and the impact of Sturge-Weber syndrome on quality of life, several studies have investigated possible strategies to address these challenges. Sebold et al ⁴⁰ reported improvements in quality of life related to depression with oral sirolimus, whereas others^44,45 reported improvements in mood and behavior with cannabidiol. Additionally, early laser treatment for port-wine stain reduction may help mitigate the social stigma associated with facial birthmarks, potentially alleviating some of the psychosocial burden. Overall, multidisciplinary treatment is essential to properly address the complex physical and mental health challenges faced by many individuals with Sturge-Weber syndrome.

In addition to these medical therapies, several studies emphasize the importance of creating a strong support system for Sturge-Weber syndrome patients, particularly during childhood and adolescence. Sujansky et al ¹⁸ suggested that early parental education about emotionally supporting their children may be beneficial in promoting resilience and mental well-being. Newsom-Davis and colleagues ⁵¹ also highlighted the need for a more robust health care plan for young people with Sturge-Weber syndrome transitioning to adulthood.

The high prevalence of psychiatric symptoms and conditions in this patient population highlights the need for comprehensive clinical attention. Providers should prioritize targeted interventions for psychiatric symptoms while considering comorbidities and the psychosocial needs of the family. Early studies documenting psychiatric symptoms in Sturge-Weber syndrome patients highlight the necessity of proactive psychiatric care in this population. ²⁵ Evidence supports the use of standard psychopharmacologic regimens for patients with Sturge-Weber syndrome; however, careful monitoring of potential interactions is crucial, in terms of both the potential effects of psychiatric medications on the seizure threshold and potential pharmacokinetic interactions, particularly with antiepileptic medications. ²¹ Overall, this report stresses the importance of a multidisciplinary treatment team and response with a robust psychiatric representation for patients with Sturge-Weber syndrome.

Strengths and Limitations

This scoping review provides a much-needed synthesis of the existing literature on psychiatric symptoms and disorders in patients with Sturge-Weber syndrome. To obtain a broad overview of existing research, we conducted a comprehensive database search using inclusive terminology, such as “Sturge-Weber syndrome,” rather than focusing on more specific terms like “psychiatric” and “depression.” In doing so, we hoped to capture all articles discussing psychiatric and behavioral symptoms of Sturge-Weber syndrome.

As a scoping review and because the topic of this review is in its infancy (eg, approximately half of reports are case reports or series), the primary aim was to summarize the available literature rather than critically appraise the quality of evidence or assess the methodologies employed. Consequently, this review does not provide a formal quantitative synthesis or critical evaluation of study designs, which may limit the depth of interpretation of the findings. Additionally, there are several methodologic limitations. First, the process of electronically searching the literature by only 2 reviewers may have introduced human error, potentially omitting relevant studies. The restriction to English-language studies further limits the scope, as important research published in other languages may have been excluded. Finally, the decision to include only peer-reviewed publications excludes potential insights from unpublished or non–peer-reviewed studies, which could have enriched the overall scope and findings of the review.

Conclusions

The existing literature on the psychiatric manifestations of Sturge-Weber syndrome demonstrates that psychiatric symptoms and behavioral issues present a significant burden to patients and families, although more comprehensive studies must be done to better understand their prevalence and clinical characteristics. In the future, studies with larger sample sizes and that use structured diagnostic interviews administered by clinician interviewers (rather than self-report) can help to standardize findings and provide a more accurate representation of psychiatric disorder prevalence in Sturge-Weber syndrome patients. Finally, a multidisciplinary approach, with a stronger emphasis on psychiatric expertise, is crucial for improving care and outcomes for individuals with Sturge-Weber syndrome.