Comprehensive Review of Worster-Drought Syndrome as a Congenital Suprabulbar Paresis

Abstract

Worster-Drought syndrome (WDS), also known as congenital suprabulbar paresis, is a rare neurodevelopmental disorder characterized by feeding, swallowing, drooling, and speech disturbances. Currently, it is classified as a subtype of cerebral palsy. However, the limited number of studies and the clinical and radiological overlap with related entities such as congenital bilateral perisylvian syndrome (CBPS) and Foix-Chavany-Marie syndrome (FCMS) have contributed to persistent uncertainty regarding its proper classification. In this review, we summarize the current knowledge on the WDS based on data from published case series. Special emphasis is placed on proposed etiological mechanisms, including recent genetic findings potentially contributing to WDS, as well as on the diagnostic process, ongoing classification dilemmas, and spectrum-based perspective. We point out the need to establish standardized diagnostic criteria and conduct large-scale genetic and neurodevelopmental research. Addressing these gaps may help clarify the underlying pathophysiology, reappraise the classification framework, and ultimately minimize misdiagnosis and time to proper diagnosis to improve outcomes for individuals affected by WDS.

1. Introduction

Worster-Drought syndrome is a congenital pseudobulbar paresis [1], which results from abnormal development of the inferior (lateral) primary motor cortex and its connections to the cranial nerve nuclei (microscopic defect), leading to impaired central control of the muscles of the face, tongue, pharynx, and larynx.

Worster-Drought syndrome (WDS) was first described by English neurologist Cecil Charles Worster-Drought in 1956 as congenital suprabulbar paresis [2]. His research focused on children with severe speech and swallowing disorders, whose symptoms did not result from damage to the lower motor neurons (cranial nerve nuclei) but rather reflected bilateral upper motor neuron lesions—particularly within the corticobulbar tract, leading to weakness or paralysis of the muscles of the lips (orbicularis oris), tongue, soft palate, pharynx, and larynx, along with an overly active jaw jerk reflex. He initially reported 82 cases [2] of that condition, including 17 cases that came from seven affected families. One of these families was further described by Patton et al., who identified four affected males [3]. The characteristics of WDS were further thoroughly detailed in Worster-Drought’s review of 200 cases [4].

Currently, WDS affects approximately 1/25,000–30,000 children, depicting male predominance, and represents about 1% of all cases of cerebral palsy [5,6]. It is characterized by an upper motor neuron pathology of muscles supplied mostly by cranial nerves X and XII but also VII. This neurological abnormality leads to classic symptoms described by Worster-Drought, such as impaired language and tongue movements, longstanding drooling, dysphagia, and speech disturbances associated with additional impairments suggesting cortical involvement (mild spastic tetraplegia or epilepsy) and, occasionally, congenital limb contractures [7,8]. Neurodevelopmental and neuropsychiatric features may include cognitive impairment, language dysfunction, autism spectrum disorder, and attention-deficit hyperactivity disorder [8]. The most common secondary complications of pseudobulbar palsy are gastroesophageal reflux, aspiration, middle ear infections, and dental malocclusion [9,10]. The majority of those symptoms are due to impaired movement of the orbicularis oris muscle, the tongue, and the soft palate [3]. Crucially, the WDS phenotype is non-progressive [6]. To differentiate WDS from other congenital pseudobulbar pareses—most notably developmental bilateral perisylvian dysplasia—clinicians highlight that WDS typically features an asymmetrical clinical presentation, appearing more “one-sided” in its physical symptoms [11]. It is yet to be discovered what might be a cause of psychomotor impairment—whether it is equally multicausal or one pathogenic variant plays a major role [12,13].

This study aimed to provide a comprehensive review of current knowledge on WDS, emphasizing novel genetic insights, hypothesized pathophysiological mechanisms, and the need for a revised diagnostic and classification framework.

2. Genetics and Pathophysiology of WDS

WDS is primarily considered a developmental disorder of the lower part of the primary motor cortex and its connections to cranial nerve nuclei, according to visible clinical phenotype. Traditionally, some authors have defined WDS by the absence of structural abnormalities in the perisylvian region on neuroimaging, whereas others have included patients with detectable cortical malformations [14]. This diagnostic inconsistency reflects ongoing debate regarding the nosological boundaries of WDS and is discussed in detail in a later section. From a pathophysiological perspective, however, WDS may be best understood as part of a continuum of developmental abnormalities affecting the lower motor cortex and perisylvian region, in which the clinical phenotype depends on the timing, extent, and severity of disrupted cortical development rather than on the mere presence or absence of macroscopic MRI abnormalities.

The underlying pathophysiology is thought to involve abnormal neuronal migration, disrupted cortical lamination, and impaired organization of cortical circuits. Purkayastha proposed that WDS may arise from neuronal migration defects accompanied by neuromotor delay and subtle perisylvian dysplasia, resulting from abnormal organization of neurons within the cortical lamina after the completion of neuroblast migration from the germinal zone and through the intermediate zone during brain development. In this context, it is suggested that polymicrogyria may result from early intrauterine ischemic injury or vascular disruptions occurring prior to the completion of cortical organization [15,16]. Additionally, the migration hypothesis is that in the described case, WDS was associated with ectopia of the neurohypophysis and hypoplasia of the pituitary gland [15]. Also, authors hypothesized that vascular abnormalities, possibly leading to anoxia or ischemia during organogenesis, might create a basis [7,17].

Familial occurrence has been reported in 6–20% of WDS cases, supporting a potential genetic contribution to its pathogenesis [1]. Clark et al., in their studies on 19 multiplex families, concluded that Worster-Drought syndrome might be of autosomal recessive or X-linked inheritance [7]. It is because in first-line cousins, a boy and a girl, both presented syndromes, where the boy suffered more severely. Previously, other inheritance patterns, such as autosomal dominant with incomplete penetrance, were suggested [3]. Moreover, Patton et al. suggested genes for WDS might be dependent on environmental factors, because one of the members of a three-generation family developed symptoms after an acute illness at the age of two [3]. Both Suresh et al. and Clark et al. mentioned the fact of similarity in cortical anatomy abnormalities in both WDS and 22q11 deletion (DiGeorge syndrome), further supporting a shared developmental vulnerability of cortical organization [8,17].

The genetic basis of WDS remains largely undefined, and no causative genes have been established to date. Several candidate genes and loci have been proposed for CBPS, including NUS1, SCN3A, TUBA1A, TUBB2B, DDX23, WFS1, ADGRG1, PI4KA, SRPX2, CCND2, DYNC1H1, biallelic variants in WDR62, and a locus on Xp28 [18,19].

Anecdotal associations have been described for LINS and Emx1, based on isolated case reports. LINS expression has been confirmed in the human fetal brain, and this gene is linked to the Wnt signaling pathway, which participates in cell proliferation, apoptosis, differentiation, migration, polarization, and other cellular processes. Mutations of the Wnt pathway, among others in EXM2, are implicated in human neurodevelopmental diseases [1]. Genes suspected to be involved in abnormal processes are those expressed in the developing cortex near the end of the period of neuronal migration or those in the germinal zone during periods of neuronogenesis. Based on mouse models of human orthology, Emx1 is considered a candidate gene for polymicrogyria due to its fundamental role in cortical development [20]. However, current evidence linking either LINS or Emx1 directly to WDS is limited and insufficient to consider them established causative genes.

Accordingly, genetic testing is gaining relevance, particularly in atypical, familial, or diagnostically ambiguous cases. While such testing cannot definitely confirm WDS due to the lack of established causative genes, it can help both to exclude other neurodevelopmental disorders and to identify potential genetic causes, which may contribute to understanding the etiology of WDS and connected syndromes.

To provide a comprehensive overview of our findings, we have developed a conceptual framework (Figure 1) that integrates the underlying genetic architecture with the identified pathophysiological pathways and their diverse clinical manifestations.

3. Diagnosis

Currently, there are no formal diagnostic criteria for WDS. The diagnostic process is mainly based on a clinical history, neurological examination, and speech and language assessment. Additional investigations, including neuroimaging, EEG, and genetic testing, are employed to support the diagnosis and to exclude other conditions with a similar presentation [21]. Importantly, the absence of standardized diagnostic criteria, the rarity, and, especially, the lack of awareness of this disease often lead to delays in diagnosis. The average age of diagnosis is approximately five years, despite the presence of symptoms often dating back to infancy. While early diagnosis is crucial for timely intervention, clinicians should be aware that motor findings in very young children can sometimes be transient or evolve with further neurological maturation [10].

MRI remains the primary neuroimaging modality, mainly to exclude structural brainstem abnormalities characteristic of true bulbar palsy. In a subset of patients, cortical malformations—most notably perisylvian polymicrogyria—have been identified in association with WDS.

Clark et al. [21] reported that 32% (12/37) of patients exhibited abnormal neuroimaging findings, including five cases of bilateral perisylvian polymicrogyria, and other case studies showed similar results regarding neuroimaging, as shown in

Table 1. Summary of available data on individuals with WDS arranged chronologically.

Study and Year	Number of Patients with WDS	Main Symptoms	Epilepsy	Genetic Findings or Family History	MRI Findings	Other
Worster-Drought, Congenital Suprabulbar Paresis. 1956 [2]	82 cases, out of which 32 showed the complete syndrome	Excessive drooling Dysarthria Inability to “round” lips (severe cases) Tongue immobility (severe cases) Paralysis or weakness of the soft palate (most frequent example)	No data	Seven familial examples of the disorder	No neuroimaging	The first description of congenital suprabulbar palsy described by Worster-Drought. In 26 cases, the soft palate was mainly or exclusively affected. In 10 cases, the tongue and palate were mainly affected. In 8 cases, the tongue and orbicularis oris were mainly affected. In 6 cases, the palate and orbicularis oris were mainly affected. Most of the children suffering from congenital suprabulbar paresis were of average intelligence
Patton et al., “A Family with Congenital Suprabulbar Paresis (Worster-Drought Syndrome)”. 1986 [3]	4 males	Suprabulbar paresis Dribbling Poorly swallowing Limited tongue movement	Three of the four patients had epilepsy, and the fourth had an abnormal EEG	Members of three generations of one family; hypothesis of autosomal dominant inheritance with variable expression and penetrance	No neuroimaging	Transmission through unaffected males to their male—suggestion that X-linkage inheritance is unlikely One of the patients with delayed onset (compared to other relatives) after an acute illness in the second year
Clark et al., “Worster-Drought Syndrome, a Mild Tetraplegic Perisylvian Cerebral Palsy. Review of 47 Cases”. 2000 [20]	47	Bulbar problems Dribbling—86% Pyramidal signs— 91% Glue ear— 60%	28%	6 children with family history	32% had abnormal neuroimaging, 14% had bilateral perisylvian polymicrogyria	Abnormal EEG—35% No speech—41% Soft, prepared diet—53% Significant medical problems in first year of life—52% Mean age of diagnosis when 6 years old Over half of the children had significant medical problems in the first year
Voorendt et al., “Twee kinderen die kwijlen”. 2009 [22]	Two girls, 5 and 13 years of age	Excessive drooling Dysarthria Dysphagia in the youngest girl and a mild right-sided hemiparesis in the oldest girl	-	-	Bilateral perisylvian ischemic abnormalities	-
Clark et al., “Congenital Perisylvian Dysfunction-Is It a Spectrum?” 2010 [8]	70 had WDS of the total 121 (81 males, 40 females; mean age 5 years, 5 months)	Pseudobulbar palsy—100% Pyramidal signs—92% Weaning difficulties—85.7% Gastroesophageal reflux—66.7% Inappropriate drooling—91.8%	39.3%	Family history of index condition—6% Family history of speech problems—14.5% Family history of epilepsy—14.5%	Normal perisylvian imaging	No speech— 56.6% Autistic spectrum disorder—18.2%
Clark et al., “Worster-Drought Syndrome”. 2010 [10]	42 (26 males, 16 females; mean age 7 y, 10 mo)	Severe bulbar dysfunction Drooling problems during feeding—95.1% Feeding difficulties—85.7% Unintelligible speech— 60.5%	30.8% Abnormal electroencephalography—40.6%	Familial history of WDS (4/36 families)—11.1% Speech delay (5/36 families)—13.9% Seizures (9/36 families)—25%	Perisylvian polymicrogyria- 13.5%	Neurogenic bulbar electromyography—38.5% Autism—19% ADHD—30%
Patil et al., “Profile of Worster Drought Syndrome (WDS)”. 2022 [16]	83 (males 52, females 31)	Drooling—79.51% Developmental delay— 100% Expressive speech delay—100% Spasticity	52.60%	Family history of speech delay in—2 families, 1 child- had an affected sibling with the perisylvian syndrome 4 were born of second-degree consanguinity, 9 were born of third-degree consanguinity	Perisylvian gliosis in 96.38% Bilateral perisylvian polymicrogyria— 3.61% Occipital lobe involvement— 84.33%	Birth asphyxia was present in 86.70% Mean age of diagnosis— 7.3 years

.

EEG is frequently employed, especially in younger children, due to the clinical overlap with epileptic syndromes. Studies have shown a co-occurrence of epilepsy in 28% to 53% of WDS cases (

Table 2. Diagnostic methods in the evaluation of Worster-Drought syndrome (WDS).

Domain	Features Suggestive of Worster-Drought Syndrome (WDS)
Medical history	Persistent difficulties with feeding, swallowing, speech, and saliva control since infancy; may also present with decreased IQ, learning difficulties, and diagnoses such as ADHD or autism spectrum disorder [10,21,23]
Neurological examination	Bilateral facial diplegia, prominent pseudobulbar signs, dysarthria, drooling, exaggerated jaw jerk reflex [2]
Speech and language assessment	Significant articulation impairments; difficulties with chewing and swallowing
Brain MRI	Often normal; in some cases, findings such as perisylvian polymicrogyria [21,24] or perisylvian gliosis [16] are observed
EEG	Epileptiform activity reported in approximately 30–50% of cases, especially in the presence of cortical malformations; may lead to misdiagnosis of primary epilepsy [16,21]
Genetic testing	Indicated for differential diagnosis in cases of unclear clinical picture; recommended particularly in atypical presentations or familial cases
Comorbidities	GERD present in 41% of children; may exacerbate pseudobulbar symptoms and contribute to misdiagnosis as a gastrointestinal disorder [16] Glue ear in 60% of patients [21] Neuropsychiatric problems in 41% of patients [21]

), with a higher prevalence among patients with structural abnormalities evident on MRI [16,21]. The presence of epileptiform activity on EEG may lead to premature diagnostic closure, with misdiagnosis and delayed referral for neuroimaging and multidisciplinary rehabilitation.

Inclusion criteria: clinical diagnosis of WDS (patients must present with the hallmark features of congenital suprabulbar paresis, including dysarthria, impaired tongue mobility, and/or excessive drooling); only case series with ≥2 patients were considered. Case reports concerning a single patient were excluded. Where multiple patients participated in the study, but insufficient data were provided to complete the subsequent columns, these reports were also removed. We performed a systematic search of PubMed, Scopus, and Embase databases for a series of cases of WDS published between 1956 and 2025. The search strategy included terms such as ‘Worster-Drought syndrome’, and ‘congenital suprabulbar paresis’.

4. Differential Diagnosis

The differential diagnosis of WDS primarily relies on an evaluation of the clinical phenotype, neuroimaging, and clinical and family history, with an emphasis on symptoms present since infancy, facilitating the exclusion of acquired or progressive disorders. In clinical practice, pediatric neurologists typically consider entities affecting the corticobulbar pathway and cortical malformations, as well as genetic neurodevelopmental disorders, childhood apraxia of speech, bulbar palsies (associated with lower motor neuron lesions), and structural anomalies such as submucous cleft palate [10]. This comprehensive approach is essential to avoid diagnostic errors that may lead to the misidentification of WDS or other syndromes with similar features [5].

Congenital bulbar palsy can display symptoms not only from bulbar motoneurons, but also there are cases showing sensory loss with a hypoactive gag reflex due to affectation of afferent neurons [25]. Incorrect function of autonomic neurons may lead to excessive salivation [26].

In congenital pseudobulbar palsy, involvement of the reticulospinal tracts may also occur, leading to decreased muscle tone (hypotonia) [27].

Polymicrogyria is depicted as an excessive amount of gyri on the surface of the cerebrum [28]. In different gene mutations of polymicrogyria, various neurons may be affected during migration of cortical cells, leading to heterogenous features of the disease [29]. It is similar in the mutation of TUBB3-based tubulinopathy, with features such as disorganization and malformations of the cortex, cortical interneurons and the brainstem [30]. In the mutation of GPR56, specifically pyramidal cortex neurons are disturbed, as well as Cajal–Retzius cells [31]. The SRPX2 gene is specific for glutaminergic neurons, and that is why those are responsible for symptoms [32].

In all Angelman, FOXG1 and Rett syndromes, GABAergic neurons may be affected, leading to hyperactivity of neuronal circuits as well as projection neurons. In Angelman syndrome, there are also deficits in myelinization and development of white matter in the brain [33,34,35,36].

Childhood apraxia of speech is not a disease of motoneurons [37].

5. Classification Dilemma

WDS meets the criteria for cerebral palsy owing to non-progressive disturbances during the early stages of brain maturation or development [10]. In ICD-10, it was classified under “G80.8-, Other cerebral palsy”, whereas in the current ICD-11, it has been assigned a distinct code (8D23) within the cerebral palsy category [38].

A major point of controversy lies in the classification of WDS within the other various syndromes that have been used in the literature to describe similar or related phenotypes and MRI findings. These include: congenital bilateral perisylvian syndrome (hereafter: CBPS), bilateral central macrogyria, bilateral opercular polymicrogyria, bilateral perisylvian dysplasia, open opercular syndrome, and developmental Foix–Chavany–Marie syndrome (hereafter: developmental FCMS) [11]. Mentioned entities are presumed to result from neuronal migration disorders and dysfunction of the corticobulbar pathway within the perisylvian cortex, producing overlapping clinical presentations [5,15,39]. Some authors indeed suggest that WDS, CBPS, and developmental FCMS represent a continuum within a broader spectrum of perisylvian dysfunction, differing in the severity of clinical manifestations, frequency of presence of neuroimaging abnormalities, and underlying etiologies—including genetic, environmental, and infectious factors [12,13,21,40]. To further understand this spectrum, it is essential to present how each of these disorders has been defined.

WDS is primarily a clinical diagnosis based on the specific symptoms described in Section 1. FCMS, also known as anterior operculum syndrome (AOS), is a clinical diagnosis characterized by speech apraxia and bilateral central paralysis of the facial, lingual, velar, and pharyngeal muscles, with a dissociation between automatic and voluntary movements. FCMS may occur in both congenital and acquired forms, with a wide range of underlying etiologies, including strokes [11,41]. However, neuroimaging studies, such as those by Cellerini et al. (1995), have been instrumental in identifying that the congenital presentation of FCMS is frequently associated with specific bilateral cortical malformations, providing a radiological link between the clinical symptoms and developmental brain anomalies [42].

In contrast, CBPS was first described by Kuzniecki et al. as a congenital form of pseudobulbar palsy, defined by the presence of bilateral perisylvian polymicrogyria on MRI, making it a radiologically defined diagnosis [43]. It is the most commonly described form of polymicrogyria, classified among malformations of cortical development (MCDs) [44].

CBPS and developmental FCMS have been described in the literature as synonymous with WDS [45,46], and Christen et al. proposed that the whole spectrum of opercular syndrome in children—both congenital and postencephalitic forms—should be unified under the term WDS [11]. Due to similar clinical phenotypes, Clark et al. argued that WDS and bilateral perisylvian syndrome represent the same condition [21]. Subsequently, Clark et al. proposed the umbrella term, congenital perisylvian dysfunction, to encompass the clinical phenotype of WDS with other related perisylvian syndromes [8]. The spectrum may be characterized by varying degrees of clinical severity and by the presence or absence of neuroimaging abnormalities such as perisylvian polymicrogyria or perisylvian gliosis [8,16]. Importantly, the authors emphasized that clinical presentation, rather than radiological findings, remains the most robust predictor of functional prognosis [8,16]. This underscores the need for meticulous clinical assessment even when the MRI appears normal.

Notably, not all researchers agree with this unified classification. Queirós et al., for instance, argue that WDS and FCMS (congenital and acquired types) represent separate disease entities [47]. Similarly, Suresh et al. note that although these conditions (WDS, CBPS, FCMS) share similar symptom profiles, differences in onset, etiology, and clinical course allow for relatively straightforward differential diagnosis [17].

Clark et al. suggest that epilepsy may influence the clinical phenotype. Focal seizure activity, even in cases with unilateral MRI abnormalities, may functionally affect bilateral motor networks by involving contralateral homologous regions. It has been hypothesized that such bilateral dysfunction may result from asymmetric timing of a genetic effect during early brain development, producing structural abnormalities on one side and subthreshold alterations on the other, undetectable by standard MRI but capable of lowering the epileptic threshold [7]. The contribution of epileptic encephalopathy to the expression and severity of WDS and related conditions remains a largely unexplored but clinically significant area.

6. Treatment

The treatment of Worster-Drought syndrome is difficult and requires an interdisciplinary approach, as it is, so far, only symptomatic [1,10,16,48]. In cases where WDS is associated with epilepsy, seizures are usually controlled with antiseizure medications; however, the available literature is limited to reports of single cases in which good therapeutic outcomes were achieved with agents such as topiramate, carbamazepine or phenytoin [16,46,49].

Treatment of gastroesophageal reflux and recurrent pneumonia diseases includes the use of proton pump inhibitors and dopamine antagonists [50]. Another drug that is used in patients with WDS is Glycopyrrolate—used for drooling with roughly 70% (60 of 83 patients) efficacy [16].

However, some medications used to treat WDS have such adverse side effects that several of the patients give up using them and decide to use behavioral techniques, e.g., while eating, such as proper chin position, regular wiping of saliva from the mouth, and conscious, fully controlled swallowing [1,10,16,48]. Operations such as surgical transposition of the submandibular duct, when attempted, did not bring the expected results [10]. To date, intensive speech therapy has shown promising results in the management of dysarthria in some patients. This approach focuses on improving respiratory and phonatory effort, modulating speech rate, and managing phrase length. For the management of dysphagia, nutritional counseling and dietary modifications are indicated; these include providing texture-modified (soft or minced) foods or, in cases of severe impairment, implementing enteral nutrition via a feeding tube [1,10,16,48].

7. Discussion

Over the years, the understanding of WDS has evolved from viewing it as a form of congenital pseudobulbar palsy [2,4] to considering it as part of a broader spectrum of perisylvian cortical developmental disorders [12,13].

The overlapping clinical and neuroimaging features observed in WDS, CBPS, and developmental FCMS strongly support the mentioned view that these entities may represent a spectrum rather than distinct disorders. The umbrella term, congenital perisylvian dysfunction, proposed by Clark et al. [8] highlights shared core features such as congenital pseudobulbar symptoms, oromotor dysfunction, and impairments in speech and swallowing, with the possible presence of perisylvian cortical malformation.

Our review supports and expands upon this spectrum-based perspective by highlighting that WDS may occur with MRI findings and share clinical features with related conditions (Figure 2,

Table 3. Differential diagnosis of WDS.

Group of Disorders	Specific Conditions	Similarities to WDS	Differentiating Features
Lower motor neuron (bulbar) syndromes	Congenital bulbar palsy [10]	Drooling, swallowing difficulties, dysarthria	Flaccid, atrophic tongue, absent jaw reflex, LMN lesion, Usually, evident brainstem structural changes
Brain malformations	Lissencephaly, various types of polymicrogyria [11,44,51]	Speech disorders (lissencephaly [52]—55%) Feeding difficulties (lissencephaly [53]—majority) Seizures (lissencephaly [52]—90%)	Extensive cortical abnormalities on MRI, more severe neurological impairments, often profound cognitive deficits
Neurodevelopmental syndromes with prominent speech and motor involvement	Angelman syndrome Rett syndrome FOXG1 syndrome [10]	Severe speech impairment (100%–Angelman [54]) (100%–Rett [55]) (100%–FOXG1 [56]); the initial presentation may resemble/overlap WDS	Genetic confirmation, often additional global developmental symptoms, variable clinical and imaging presentations
Speech disorders	Childhood apraxia of speech (CAS) [57]	Articulation difficulties (50–85% [58]), delayed speech development (100% [59])	No muscle weakness, normal MRI
Structural oral cavity defects	Submucous cleft palate [10]	Drooling, feeding difficulties (48–85% [60])	Defects visible on ENT exam or imaging, no CNS abnormalities, no neurological symptoms

). Notably, some authors continue to define WDS primarily based on the absence of structural abnormalities on imaging [14], despite others reporting detectable imaging changes such as perisylvian polymicrogyria or perisylvian gliosis [21,24]. This inconsistency underscores the need for a clearer, standardized spectrum-based diagnostic model that integrates clinical phenotype, neuroimaging findings, and genetic data.

Currently, the diagnostic approach relies mainly on a clinical history, neurological examination, and specialized assessments of speech and language. Further investigations, such as neuroimaging and genetic testing, are used to confirm the diagnosis and exclude other disorders with overlapping clinical features [21]. Nevertheless, no universally accepted diagnostic criteria currently exist, and the syndrome’s classification remains debated in the literature.

The etiology of WDS is still not completely understood. In the literature, various potential mechanisms underlying the development of WDS are described. Neuroimaging studies frequently reveal bilateral perisylvian polymicrogyria, suggesting a congenital cortical malformation as the underlying cause [21]. However, some patients present with normal structural imaging, raising the possibility of subtle cortical migration disorders or functional cortical impairment.

As we mentioned in the previous paragraph, familial occurrence of WDS occurs in 6–20% of cases; therefore, the involvement of a genetic factor in some patients is highly probable [1]. However, the strength of the current genetic evidence remains limited. Among the genes that have been proposed as potential candidates is EMX1, which is involved in neuronal migration and has been hypothesized to play a role in the development of WDS. Another gene that has been suggested in this context is LINS, potentially through its involvement in the Wnt signaling pathway; however, the available evidence supporting this association remains preliminary [7,15]. Despite these few findings, the majority of cases remain genetically unexplained, indicating a likely multifactorial origin.

Currently, treatment for WDS remains symptomatic, focusing on speech and language therapy (including neuro-speech pathology), feeding interventions, and physical therapy. There is no curative treatment available at this time. Pharmacological management is tailored to comorbid and distressing symptoms, such as gastroesophageal reflux or epilepsy. Early diagnosis is crucial, as it facilitates the implementation of an optimized care plan and significantly enhances the patient’s quality of life.

Neurological rehabilitation, feeding therapy, and—when necessary—antiepileptic treatment are also important components of care. However, there are no standardized treatment protocols, and little evidence exists regarding the long-term outcomes of various therapeutic interventions.

Future therapeutic research should focus on the development of pharmacological agents characterized by a lower incidence of adverse effects, thereby improving patient adherence and reducing treatment discontinuation. Furthermore, it is essential to devise more effective surgical interventions to enhance clinical outcomes in areas such as the management of drooling, where current operative methods, such as surgical transposition of the submandibular duct, often fail to yield satisfactory results.

Limitations in the actual state of knowledge on the topic are diverse. Generally, there is a lack of population studies. Those should bring much more information on the characteristics of afflicted people. Currently, most available data comes from a small number of case studies, which makes it difficult to draw definitive clinical conclusions or reach a consensus on best practices. Gaining insight into long-term treatment outcomes from previous cases would be beneficial for managing future patients, as it would highlight the relative advantages and disadvantages of various interventions.

The proposed diagnostic pathway algorithm (Figure 3) is designed to streamline clinical recognition and prevent the omission of Worster-Drought syndrome (WDS). The process begins with identifying a child with speech and/or swallowing difficulties that have been present since infancy and follow a non-progressive clinical course. A key element of the neurological examination is the identification of pseudobulbar signs (upper motor neuron involvement) in the absence of lower motor neuron features, which helps exclude primary neuromuscular diseases. The speech and swallowing assessment should identify severe dysarthria, dysphagia, and/or features of childhood apraxia of speech (CAS). Including both dysarthria and CAS ensures broader diagnostic sensitivity, as these terms are not synonymous and indicate different pathophysiological mechanisms. The subsequent step involves brain MRI, which may show normal findings or perisylvian abnormalities. Following the exclusion of other causes and optional genetic testing, a clinical diagnosis of WDS is established.

8. Conclusions

In summary, Worster-Drought syndrome remains a disorder that is difficult to classify unequivocally and requires a broad interdisciplinary approach for accurate management. There is an urgent need to develop formal diagnostic criteria, genetic screening panels, and diagnostic–therapeutic algorithms. Early identification of WDS is crucial for improving patients’ quality of life and the effectiveness of therapy. To prevent diagnostic omission, clinicians must maintain a high index of suspicion in children presenting with persistent neonatal feeding difficulties and significant receptive–expressive language gaps, even when structural neuroimaging appears normal. To support this clinical process, we provide a proposed diagnostic pathway algorithm (Figure 3), designed to serve as a practical tool for early identification and to prevent the omission of WDS. Future research should focus on identifying diagnostic biomarkers, gaining a better understanding of the genetic basis, and conducting long-term evaluations of therapeutic outcomes.