Case Report: Sustained Cognitive Improvement and Reversible Brain Hypoperfusion in the Context of Posterior Fossa Arachnoid Cyst Shunting Procedure in KBG Syndrome

Abstract

KBG syndrome is a genetic syndrome characterized by developmental delay, mild autism spectrum disorder (ASD), variable cognitive disorders and distinctive craniofacial and skeletal features. Posterior fossa arachnoid cysts (PFACs) have been reported in this condition as in other syndromic forms of ASD, but their impact remains uncertain. Here, we report a ten-year follow-up of a patient with KBG syndrome and PFAC shunted for progressive cyst enlargement and his clinical symptoms, who showed important cognitive and behavior improvement post-drainage. Preoperative neuropsychological assessment revealed severe ASD, heterogeneous cognitive profile with below-average IQ (82, average ≥90), slow processing speed (66, cut-off <70), prominent executive function and memory impairments but normal verbal index and working memory. Whole-brain arterial spin labelling MRI showed a markedly reduced cerebral blood flow in the left superior temporal sulcus (STS), a key region for social cognition. Eighteen-month post cystoperitoneal shunt, cyst volume had decreased (34 vs 10 mL), STS perfusion was no longer different from controls and high cognitive improvements were observed (IQ: +1SD, verbal index: +2SD, executive functions planning and flexibility: +3SD, emotional regulation: +1SD, verbal memory: +3SD). At 22 years, autistic traits had decreased, cognitive gains persisted and executive functions progressed again. Visual-motor processing speed, theory of mind and fine motor skills remained low. Resting-state functional MRI seeded from STS showed strengthened temporal connectivity and diffusion imaging revealed increased fibre density in the left temporal lobe. The parallel trajectories of behavioural and neuroimaging improvements may suggest that PFAC surgery could have enabled functional reorganisation within temporal networks in addition to therapeutic interventions, supporting improved cognitive and social outcomes. These results suggest a possible role of the posterior fossa in modulating neurodevelopmental outcomes in ASD-related genetic conditions.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1007/s12311-026-02083-2.

Introduction

KBG syndrome (MIM #148050) is a rare, clinically recognizable condition caused by pathogenic variants in the ANKRD11 gene (the initials K, B, and G are those of the first three reported patients). This syndrome is characterised by a recognisable association of macrodontia of the upper central incisors, distinctive craniofacial features, short stature, skeletal and hand anomalies, developmental delay and motor difficulties [1, 2]. Intellectual functioning is frequently affected with marked interindividual variability, severe intellectual disability remaining less than 3% of the patients [3, 4, 5]. Attention-deficit/hyperactivity disorder are commonly reported in adults, alongside autistic traits, anxiety, emotional dysregulation and oppositional behaviors. Epilepsy occurs in a subset of patients [2, 5, 6]. While autistic traits are frequents in KBG syndrome, a formally diagnosed autism spectrum disorder remains considerably less frequent [6].

Intracranial cysts, particularly posterior fossa arachnoid cysts (PFACs) have been reported in KBG syndrome [7, 8, 9] as in other syndromic forms of ASD involving the ARID1B and FOXP1 genes [10]. PFACs are frequently regarded as incidental findings and their potential impact on neurocognitive development remains elusive [11, 12]. While a few reports suggest that cyst shunting procedure may be associated with developmental gains [13, 14], the benefits of PFAC surgery have not been documented in KBG nor in other ASD-related genetic conditions to date.

Here, we combined neuropsychological assessment and multimodal brain MRI to report on long-term sustained cognitive improvement in the context of PFAC procedure in a patient with KBG syndrome. The family and the patient consented to the study, which was approved by a French ethical committee (24.00501.000307 2023-A02668-37).

Case Report

The patient, a right-handed male, was born to healthy unrelated parents after a term pregnancy (37 weeks) and normal delivery (birth weight: 2.25 kg, length: 43.5 cm, occipitofrontal circumference: 33 cm). He presented at birth with perinatal distress and hypotonia. His early development was marked by delayed milestones, gaze avoidance and recognisable facial dysmorphism. Brain MRI detected a midline retrocerebellar arachnoid cyst at 1 year, reaching a volume of 20 mL at 4 years, exerting mass effect on the vermis without compression of the fourth ventricle nor brainstem. Cerebrospinal fluid circulation appeared preserved. He walked at 3 years and said his first words at 5 years. He had restricted interests, stereotypical behaviours, and communication difficulties with logorrhoea and rigid tendencies. He had swallowing disorders and ate pureed food until 5 years old. He started orthoptic and sensorimotor therapy at the age of 8 months and speech therapy from 4 years to 9 years old. He went to ordinary school at 3 years with the assistance of a school-aid and family support.

He met the criteria for severe ASD at 9 years, as assessed using the Childhood Autism Rating Scale (CARS: 40.5), Autism Diagnostic Interview Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). Genetic whole exome sequencing identified a pathogenic de novo variant in ANKRD11 (NM_001256183.1:c.6792dup; p.(Ala2265Argfs*8), confirming the diagnosis of KBG syndrome. This variant was classified as pathogenic in ClinVar and has been reported in other affected individuals. No other genetic variation was identified. The patient continued speech and sensorimotor therapy, he also had occupational therapy to learn to write on a computer and attended a therapeutic social group at 11 years old. He was maintained in a regular school with the help of a school-aid.

A comprehensive neuropsychological evaluation conducted at 12 years (Wechsler Intelligence Scale for Children-IV, Purdue Pegboard motor test, memory and executive tests, BHK writing test, and Rey–Osterrieth Complex Figure Test and BRIEF parental questionnaire) identified a heterogeneous cognitive profile with below-average full IQ (82) and markedly reduced processing speed (66), while verbal abilities (101) and working memory skills (97) were preserved (Table 1).

Table 1.

Time course of neuropsychological assessments pre- and post-PFAC shunting procedure in the case of KBG syndrome

Domain	Test	12 Years PREOPERATIVE	13 Years POSTOPERAVTIVE	22 Years FOLLOW-UP
Wechsler intelligence scale	IQ	82	101*	103*
	Verbal comprehension	101	132**	135**
	Perceptual reasoning	81	94	88
	Working memory	97	100	128***
	Processing speed	66	66	66
Language	Similarities	0,00	2,33**	2,33**
	Vocabulary	1,33	1,66	2,33*
	Pictures naming	-2,47	-1,33*	0,23**
	Categorical verbal fluency	-1,77	-0,70*	-0,39*
Episodic memory	stories immediate recall	-3,00	0,00***	0,66***
	Stories delayed recall	-3,00	0,00***	1,33***
	List of words imm. recall	-2,66	0,66***	-1,89
	List of word delayed recall	-4,41	-2,00**	-3,14*
	Rey incident visual memory	-2,62	-1,78	-2,00
Social cognition	Wechsler Comprehension	-1,00	1,33**	1,33**
	Emotions processing	-1,00	-1,00	0,33*
	Theory of Mind	-2,80	-2,80	-1,80*
	CARS-ASD (cut-off =30)	40,5	33,5	30,5
Fine motricity	BHK writing	-2,55	0,22**	-0,70*
	Purdue motricity both hands	-4,40	-3,90	-3,29*
Executive Functions	Trail making test A	-3,45	-0,09***	-0,66**
	Trail making test B	-0,18	0,48	0,50
	London Tower execution time	-4,00	-2,09*	-0,91***
	London Tower 1st trial success	-0,81	-1,63	0,80
	Phonemic verbal fluency	-0,71	1,33*	-0,45
	Rey Complex Figure copy	-5,31	-1,38***	-1,10***
	BRIEF parental questionnaire (T score)
	Inhibition	70	66	65
	Flexibility	70	65	53*
	Emotional control	80	62*	40****
	Initiation	60	49*	59
	working memory	70	48**	52*
	Planification	60	50*	73
	Organization	50	40*	66
	Monitor	60	51	55
	Behavior regulation index	70	66	51*
	Metacognitif index	70	48**	67
	Global executive score	70	54*	61

Bold type indicates pathological scores (i.e. Wechsler index < 70, z score <-1.65 and T score ≥ 65). Asterisks (*) indicate ± 1 standard deviation compared to preoperative scores. Differences (postoperative score − preoperative score) ≥ 1 SD were considered as high improvement (gain) and differences ≤ − 1 SD as high decrease (loss). All results are in z scores, except for Wechsler scale (m = 100, sd = 15), Brief scale (m = 50, sd = 10) and CARS scale (cut-off = 30). Tests used: WISC.IV Wechsler intelligence scale for children / WAIS.IV Wechsler intelligence scale for adults, Nepsy2 A developmental Neuropsychological assessment, CMS Children memory scale stories, BEM 144 Battery of memory efficiency list of words, MEM.IV Memory adult scale stories, ROCF Rey-Osterrieth Complex Figure. Postoperative results showed ASD-score reduction and high improvements in intellectual, language, executive functions, social cognition and verbal memory domains compared to preoperative scores; theory of mind and fine motricity were still low

He was short-tempered with serious executive dysfunction (impulsivity, poor planning, and reduced flexibility), emotional dysregulation (emotional outbursts), impaired social interactions (poor theory of mind), deficits in verbal episodic memory, and motor difficulties including severe dysgraphia (Table 1).

At that time, MRI showed cyst enlargement from 20 mL to 34 mL (Fig. 1) and increased prominence of the superior vermian folia, which may have reflected either chronic mass effect or mild vermian atrophy. The patient presented with frequent headaches, significant motor and coordination difficulties including impaired ball catching, inability to ride a bicycle, and difficulties with handwriting. Behavioral and emotional difficulties were also noted, including impulsivity, reduced cognitive flexibility, emotional outbursts, and impaired social interactions. Given the progressive cyst enlargement and the clinical symptoms burden, neurosurgical intervention was recommended. The procedure performed was a cystoperitoneal shunt placement. After opening the posterior fossa cyst, a proximal catheter was inserted into the cyst cavity and connected to an Atlas valve. The distal catheter was then tunneled into the peritoneal cavity. No fenestration into the subarachnoid spaces or ventricles was performed. The postoperative course was uneventful. The patient experienced transient headaches in the weeks following shunting procedure, which resolved spontaneously without intervention. No complications were documented, including no infection, hemorrhage, overdrainage, shunt revision, or reoperation.

Fig. 1.

PFAC appearance pre and post cystoperitoneal shunt in a patient with KBG syndrome. A: pre-surgery 3DT2 and B: pre-surgery 3DT1, C: Eighteen-month post-surgery 3DT1, D: 10 years post-surgery 3DT1. (A–B) Preoperative T2- and T1-weighted sagittal MR images showing the cerebellar cyst at 12 years of age (A, B), and postoperative sagittal T1-weighted images at 13 (C) and 22 years (D), demonstrating reduction of the PFAC (34 mL vs. 10 mL) and progressive redeployment of the cerebellum

Following cystoperitoneal shunt, we retrospectively performed an arterial spin labeling (ASL) perfusion analysis to explore potential links between the cerebellar cyst and the patient’s behavioral disturbances. Its purpose was solely to generate hypotheses regarding the potential functional impact of the lesion and the mechanisms underlying the observed postoperative changes (acquisition parameters in Table 2). Cerebral blood flow (CBF) was compared between the patient and 13 age-matched healthy controls (mean age 11.4 ± 1.1 years, 9 male) drawn from our laboratory database. Controls were selected on the basis of an age-match to the patient, no reported medical history, a radiologically normal MRI, and written informed consent from the child and their family at inclusion. This control group was scanned on the same scanner and with the same protocol as our patient. The analysis was performed using a whole-brain voxel-wise approach in SPM12, with age as a covariate and an explicit cortical grey-matter mask. No region of interest was predefined. The statistical threshold was set at the cluster level at p < 0.05, family-wise-error (FWE) corrected.

Table 2.

MRI acquisition parameters across the three assessments

	12 YEARS PREOPERATIVE	13 YEARS	22 YEARS
MRI brand	General Electrics	General Electrics	General Electrics
Field strength (T)	1.5	3.0	3.0
Model	Signa HDxt	Discovery MR750	Signa Premier
3D T1-weighted
TR (ms)	12.4	6.9	6.9
TE (ms)	5.2	3.0	3.0
Flip angle (°)	13	13	13
In-plane resolution (mm)	0.43 × 0.43	1.0 × 1.0	1.0 × 1.0
Slice thickness (mm)	1.4	1.0	1.0
Number of slices	240	156	156
3D pCASL
TR (ms)	4428	4453	4453
TE (ms)	10.5	11.0	11.0
Post-labelling delay (ms)	1025	1025	1025
In-plane resolution (mm)	1.875 × 1.875	1.875 × 1.875	1.875 × 1.875
Slice thickness (mm)	4	4	4
Matrix	128 × 128	128 × 128	128 × 128
Number of slices	40	46	46
FOV (cm)	24 × 24	24 × 24	24 × 24
Diffusion
TR (ms)	—	—	7000
TE (ms)	—	—	75
Diffusion directions	—	—	60
b-value (s/mm²)	—	—	3000 (+ reversed b = 0)
Voxel size (mm)	—	—	0.86 × 0.86
Slice thickness (mm)	—	—	2.3
Resting-state fMRI
TR (ms)	—	—	1500
TE (ms)	—	—	29
Flip angle (°)	—	—	90
Voxel size (mm)	—	—	1.718 x 1.718
Slice thickness (mm)	—	—	2
Gap between slices	—	—	2 - 2
Matrix	—	—	128 x 128
Number of slices	—	—	69

MRI data were acquired at three time points: preoperatively at age 12 years (1.5T GE Signa HDxt), and postoperatively at age 13 years (3.0T GE Discovery MR750) and age 22 years (3.0T GE Signa Premier). Parameters are reported for three acquisition sequences: three-dimensional T1-weighted structural imaging, three-dimensional pseudo-continuous arterial spin labelling (3D pCASL), diffusion-weighted imaging, and resting-state functional MRI. Diffusion and resting-state fMRI were acquired at the 22-year time point only. FOV: field of view; TR: repetition time; TE: echo time; fMRI: functional magnetic resonance imaging. — indicates sequence not acquired at that time point

A single significant cluster of reduced rCBF was identified in the left superior temporal sulcus (STS; T = 8.64, Z = 4.66, pFWE < 0.05; MNI coordinates [− 62, − 38, 4]; Fig. 2). To quantify the perfusion deficit at the individual level, CBF values of our patient and his control group were extracted from this cluster and we used the modified t-test for single-case studies [15]. The patient’s CBF (30.52 ml/100 g/min) was markedly lower than that of controls (mean = 79.25, SD = 8.05; t = − 5.83, p < 0.001; Z-CC = − 6.05, 95% CI [− 8.50, − 3.60]). These findings raise the hypothesis that posterior fossa compression may have exerted some remote effects on cortical perfusion in regions critical for social cognition, given the known key role of the STS in social perception and cognition [16, 17].

Fig. 2.

Longitudinal arterial spin labelling pattern pre and post PFAC shunting procedure in a patient with KBG syndrome. 3D views of the significantly decreased regional cerebral blood flow (rCBF; in blue) in the left superior temporal sulcus (circles) obtained from a whole brain voxel wise arterial spin labelling analysis comparing our patient at 12 years of age with an age-matched control group before surgery P<0.05 FWE (A). Longitudinal dotted lines after surgery highlight that there were no longer differences in rCBF at rest between our patient and controls (B: 13 years; C: 22 years)

Eighteen months post cystoperitoneal shunt (13 years), the cyst had decreased in volume to 10 mL (vs. 34; Fig. 1). Age-standardised neuropsychological tests, using the exact same protocol, revealed noticeable improvement in patient IQ from 82 to 101 (+ 1SD), and verbal Wechsler index rose from 101 to 132 (+ 2SD). Episodic verbal memory improved importantly (+ 3SD), as did executive functions, with gains in planning (+ 3SD), flexibility (+ 3 SD)). He showed better self-control and parents reported fewer anger issues and reduction of emotional regulation impairments (-1SD). CARS showed a reduction of ASD score from 40.5 to 33.5 (Table 1). The patient reported that he was now able to maintain eye contact with others, which he had been unable to do prior to surgery. His family reported better organisation of his ideas with more coherent speech, less rigidity in everyday life, better memorization skills (e.g., multiplication tables), increased empathy with overall social engagement, a reduction in behavioural difficulties, and better analytical skills, consistent with the improvement observed in the Wechsler Similarities subtest (Table 1). However, visual-motor processing speed remained markedly impaired, and difficulties in theory of mind and fine motor skills persisted, consistent with the underlying KBG syndrome phenotype. He continued in a regular school and achieved satisfactory results thanks to the help of a school-aid, the use of a computer to write, and extra-time on tests. He still needed help with everyday tasks like tying his shoes, doing up buttons and going to middle school on his own. He still underwent sensorimotor therapy, occupational therapy and therapeutic social group.

Using the same whole-brain voxel-wise approach, ASL-MRI analysis performed on a 3.0T GE Discovery MR750 (acquisition parameters in Table 2) revealed no significant cluster of reduced rCBF compared to 16 age-matched controls (mean age 12.6 ± 1.5 years, 6 male; Fig. 2), drawn from our laboratory database, scanned on the same scanner and with the same protocol as our patient.

At 22 years (10 years post-surgery), cyst volume was stable at 10 mL and MRI showed cerebellum redeployment (Fig. 1). The cystoperitoneal shunt remained in place and functioned normally, without any revision or replacement since the initial cystoperitoneal shunt. The patient was considered likely to remain shunt-dependent in the long term. They were no history of seizures, unremarkable sleep, he had no auditory problems and no long-term medication. Since childhood, he wore strong corrective glasses to correct visual impairments, which may have affected his visual-motor processing speed.

The patient had discontinued all specialist follow-up approximately four years prior to the last assessment and was now actively involved in an associative socialisation group for adults with ASD. Despite the interruption of rehabilitations, he successfully completed a degree in computer science, in 3 years instead of 2 and with supplementary time for exams. He was not employed, having recently relocated with his family to a rural area and needing many working accommodations, as well as some family supervision in daily life, living with his parents due to a relative autonomy. He reported that he remained able to maintain eye contact, reflecting sustained gains in social engagement over the 10-year follow-up period (Fig. 3).

Fig. 3.

Longitudinal clinical, neuropsychological, and neuroimaging timeline. Three parallel tracks document the patient’s trajectory from birth to age 22: clinical events and therapeutic interventions (beige), neuropsychological assessments (blue), and multimodal neuroimaging findings (green). The red horizontal line marks the cysto-peritoneal shunt (age 12–13 years), the pivotal intervention. Dotted lines indicate temporal correspondence between concurrent assessments. ASL: arterial spin labelling; rCBF: regional cerebral blood flow; STS: superior temporal sulcus; rs-fMRI: resting-state functional MRI; FBA: fixel-based analysis; DWI: diffusion-weighted imaging

Neuropsychological testing (using WAIS IV) showed sustained postoperative progress (average IQ, improved verbal abilities, better planning; Table 1), and even high improvements compared to preoperative results in working memory (+ 3SD), executive speed (+ 3SD) and lexical access (+ 3SD), as well as in emotional control (-4SD). His speech was still sometimes logorrheic, with a monotonous and stuttered tone. He still had theory of mind and motor issues, but his writing skills had improved. Caregiver-reported and scale-based autistic features appeared less severe, as reflected by CARS score (30.5 vs. 40.5 prior to PFAC shunting procedure), with progress in social interactions, empathy and autonomy in daily life. Visual-motor processing speed, theory of mind difficulties, and fine motor impairments remained present, reflecting the persistence of core KBG syndrome features.

ASL-MRI analysis were performed on a 3.0T GE Signa Premier (acquisition parameters in Table 2) using the same whole-brain voxel-wise approach with 8 age-matched controls (mean age 24.6 ± 4 years, 3 male; Fig. 2), drawn from our laboratory database, included on the same scanner and with the same protocol as our patient. Those analyses failed to detect any difference from controls.

Finally, multimodal brain imaging was performed (Fig. 4) with the aim of investigating the mechanisms underlying the patient’s clinical improvement. Resting-state functional MRI analysis seeded from the STS cluster which initially showed reduced cerebral blood flow revealed strengthened functional connectivity with temporal networks compared to 12 age-matched controls (p = 0.06 FWE, Fig. 1). Diffusion MRI using fixel-based analysis demonstrated increased fibre density and bundle cross-section within the left temporal lobe and corticospinal tract compared to 12 age-matched controls (Fig. 4). Although these two findings did not survive correction, anatomical consistency with regions relevant to social cognition may suggest a compensatory neuroplastic process.

Fig. 4.

3D view of the resting-state functional MRI seeded from the STS cluster (circle), and fibre density and bundle cross-section analysis. A – B: 3D views of resting-state functional MRI, seeded from the superior temporal sulcus cluster initially showing rCBF reduction (circle), demonstrating strengthened functional connectivity with temporal networks in our patient at 22 years compared to age-matched controls. In red, enhanced functional connectivity in temporal networks in our patient compared to controls; in blue, decreased connectivity in our patient compared to controls (p=0.06 FEW). Functional connectivity results were only exploratory trends and did not survive correction. C: 10 years postoperative analysis of fibre density and bundle cross-section in a patient with KBG syndrome compared to 8 age-matched controls. Circles indicate increased fibre density and bundle cross-section in the left STS (**) and corticospinal (*) tracts in a right-handed patient compared to controls. Whole-brain fixel-based analysis of group differences in fiber density and bundle cross-section between our patient at 22 years and age-matched controls. Circles indicate increased fiber density and bundle cross-section in the left superior temporal sulcus and corticospinal tracts in our right-handed patient compared to controls. Anatomical connectivity results were only exploratory trends and did not survive correction.

Discussion

To our knowledge, no long-term neuropsychological and multimodal neuroimaging study post PFAC shunting procedure has been hitherto reported in KBG syndrome, nor in other syndromic forms of ASD. However, cognitive improvements in language, executive functioning and emotional regulation have been reported after posterior fossa cyst surgery [14] and in other forms of cerebellum-involved surgery, such as Chiari [18, 19].

The patient we report on showed important and sustained improvement post PFAC cystoperitoneal shunt over a 10-year period, especially in social domains, working and episodic memory, emotional regulation and lexical access compared to preoperative scores. The marked postoperative improvement observed in this patient was temporally associated with cyst decompression. Although causality cannot be established from a single case, we hypothesize that decompression may have facilitated functional reorganization of cerebello-cerebral networks, thereby allowing the patient to benefit more effectively from ongoing therapeutic and educational interventions. These networks are crucial for the development of social cognition and their alterations are known to be involved in autism spectrum disorders [20, 21, 22]. Reversible STS hypoperfusion, strengthened temporal connectivity, and microstructural changes in temporal lobe white matter may support a compensatory neuroplastic mechanism. These observations should be considered hypothesis-generating and cannot be used to generalize surgical indications.

These results also align with the emerging literature linking PFACs to temporal lobe hypoperfusion and impaired social functioning [23]. The structural basis for such remote effects may involve the cerebello-temporal pathway [24], which demonstrated bidirectional structural connectivity between cerebellar lobule and STS via the superior longitudinal fascicles and cerebellar peduncles. This pathway provides a plausible anatomical substrate through which posterior fossa compression could exert some remote effects on cortical perfusion and social cognition networks.

The patient initially exhibited pronounced ASD features and executive dysfunction, which are features at the more severe end of the reported KBG neurobehavioral spectrum [25]. His developmental trajectory after cyst shunting procedure shifted toward a more common course for KBG syndrome [26, 27]. Such a spontaneous improvement, even after long-term rehabilitation, is quite unusual. Hence, the improvements reported here are unlikely to reflect a natural or spontaneous progression [28]. The use of age-standardised tests with good test-retest reliability and a good correlation between the children and adult versions [29] also supports the relevance of our observation, and the long interval between each assessment ensured consistent results over time and minimised the test–retest effect.

While single-case findings must be interpreted with caution, particularly because the anatomical and functional connectivity analyses are exploratory in nature, these results should be considered cautiously. Thus, this observation suggests that cyst surgery may contribute, in addition to therapeutic interventions, to improving cognitive and social outcomes in selected neurodevelopmental cases. It highlights the putative role of the posterior fossa in modulating neurodevelopmental outcomes in KBG syndrome, and potentially in other genetic conditions associated with ASD.

Limitations

Some limitations should be acknowledged in this study. First, the single-case design precludes any generalization of the findings, and all results should be interpreted with appropriate caution.

Second, neuropsychological assessments were conducted across three time points. The preoperative and 18-month postoperative assessments used the same version of the Wechsler Intelligence Scale for Children, which may potentially introduce a test-retest effect. However, practice effects are typically reported in the range of 3 to 5 IQ points [30, 31]. Here, the observed gains of 19 points in full-scale IQ and 31 points in verbal index substantially exceed this range and are unlikely to be accounted for by familiarity with the test material alone.

The 22-year assessment use of an age-appropriate version of the Wechler-scale (WAIS-IV), could have introduced some cross-age incomparability, but the good correlation between the children and adult scales [30] and the fact that both scales share the same theoretical framework and normative metric highly mitigate this limit. Empirical studies have shown that Full Scale IQ scores obtained from the WISC and WAIS at age 16 are statistically comparable (corrected correlation of 0.89), with minimal mean differences, as their construct is made for longitudinal comparisons [32, 33]. The use of both instruments across this patient’s follow-up therefore reflects standard clinical practice in longitudinal neuropsychological assessment [33].

Third, this study involving a single patient, we didn’t perform a cerebellar whole-brain functional connectivity analysis. We focused our rs-fMRI analysis on the hypoperfused temporal region as a seed, as it represented the most clinically and functionally relevant region of interest in the context of this patient’s social and cognitive profile. Our exploratory imaging findings at the 22-year follow-up did not survive correction but the temporal findings are consistent with previous literature and do not appear to represent random observations. Although the cerebellum was included in the rs-fMRI acquisitions, cerebellar connectivity was not investigated in the present study, and this represents an interesting avenue for future research.

Fourth, the contribution of therapeutic interventions to the observed cognitive gains cannot be entirely excluded. Prior to cystoperitoneal shunt, the patient had received intensive multidisciplinary support, without achieving comparable progress. This observation raises the possibility that cyst decompression facilitated subsequent neurodevelopmental gains by enhancing the effectiveness of therapeutic and educational interventions, rather than replacing them. In this view, shunting procedure may have acted as an enabling factor within a broader multidisciplinary management strategy. Consistent with this interpretation, cognitive gains persisted and even progressed despite the discontinuation of all rehabilitations four years before the final assessment.

Although no conclusions can be drawn from a single case, these observations suggest a possible role of the posterior fossa in modulating neurodevelopmental outcomes in ASD-related genetic conditions. In selected cases, cyst decompression may contribute, alongside educational and therapeutic interventions, to improvements in cognitive and social functioning. These findings remain hypothesis-generating and require confirmation in larger studies.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

A.F. included the patient, performed the last neuropsychological assessments with M-L.C., conducted imaging acquisition for the last MRI and drafted the original manuscript.M-L.C performed the two first neuropsychological assessment and the last with A.F., and helped draft the original manuscript.L.F. and J.B. performed preprocessing and analyses of ASL-MRI, diffusion-weighted imaging data, including fixel-based analysis, and Resting State f-MRI.L.O. did the autism spectrum disorder investigations and follow-up.S.P. performed the posterior fossa surgery.V.D.-R. and S.C. reviewed all MRI data and contributed to manuscript writingA.M. provided access to the patient, allowed the genetic diagnosis and contributed to data interpretation, and revised the manuscript.A.S. and M.Z. first performed the multimodal MRI acquisition, contributed to the conceptualization of the study and revised the manuscript.N.B. first saw the cyst enlargement, asked for surgery and supervised the entire project, from patient inclusion to manuscript preparation.

Funding statement

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Patient and public Involvement

Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

Patient consent for publication

was obtained from the patient and his parents.

Competing interests

The authors declare no competing interests.