Search

This paper aims to investigate the advances in recent years in the recognition and therapy of treatment-resistant depression starting from the concepts of: depressive disorder, resistance and pseudoresistance to drug treatment in depression, and appropriate treatments of treatment-resistant depression.An extensive research was carried out on scientific databases such as: PubMed, PsychInfo and Cochrane Library, until May 2022, using the keywords "major depression", "treatment-resistant depression", "staging", "instrumental therapies for resistant depression", "esketamine" and "psilocybin".Subjects who do not respond to antidepressants show a form of treatment resistance that requires an approach with additional pharmacological and/or instrumental therapies. Recently, esketamine and psilocybin are of particular interest among clinicians, and instrumental treatments such as: vagus nerve stimulation, deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, epidural cortical stimulation, and electro convulsive therapy, are being added to them.Treatment-resistant depression has increasingly become a public health problem due to the significant number of relapses, hospitalizations and mortality it entails, with increased demand for the use of more drugs, therapeutic resources by health services, and loss of quality of life for patients. Treatment-resistant depression needs to be addressed through the creation of dedicated study protocols. Future research should focus on the need to establish operational, valid and appropriate criteria, both on the psychopathological, clinical governance and therapeutic levels, focusing on the latest therapies in order to provide reliable data on the benefits, risks and costs associated with their use.

Introduction Joubert syndrome (JS) is an autosomal recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including congenital retinal dystrophy. The function of different retinal elements (rod, cone, bipolar cells) can be objectively evaluated by electroretinogram (ERG) recordings. Our work aims to evaluate the retinal function (by ERG recordings) in patients with JS with or without congenital retinal dystrophy. In addition, since clinical trials should be performed in the near future in JS, our results could provide information about the possible usefulness of ERG recordings in the assessment of the efficacy of treatments targeted to improve the retinal involvement. Methods In this observational and prospective study, 24 children with genetic identification for JS (mean age 10.75 ± 6.59 years) and 25 healthy age-similar normal control subjects (control group, mean age 10.55 ± 3.76 years) were enrolled. On the basis of the presence/absence of retinal dystrophy at fundus examination, patients with JS were divided into two groups: patients with JS with retinal dystrophy (16 children, mean age 11.00 ± 6.74 years, providing 16 eyes; JS-RD group) and patients with JS without retinal dystrophy (8 children, mean age 10.50 ± 6.45 years, providing 8 eyes; JS-NRD group). In patients with JS and controls, visual acuity (VA), dark-adapted, light-adapted, and 30-Hz flicker ERGs were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Results When compared to controls, patients in the JS-RD and JS-NRD groups showed significant abnormalities of the values of dark-adapted, light-adapted, and 30-Hz flicker ERG parameters. The ERG and VA changes were not significantly correlated. Conclusions Our results suggest that a dysfunction of photoreceptors and bipolar cells occurs in patients with JS with or without retinal dystrophy. The retinal impairment can be detected by ERG recordings and this method should be proposed to evaluate the effectiveness of adequate treatment targeted to improve the retinal impairment in patients with JS.

The inositol 1,4,5-triphosphate receptor type 1 (

In the pediatric context, parents' and patients' engagement in the care process is strongly recommended and could be pursued using patient-reported outcome measures (PROMs), which therefore become useful for planning and monitoring treatments. Nevertheless, few data are available from families of children with neurodevelopmental disorders such as visual impairment (VI). The Visual Impairment Developmental Autonomy (VIDA) project aims to develop and validate a patient- and parent-reported tool to measure the most relevant aspects concerning everyday adaptive abilities in children and adolescents with visual impairment: the VIDA scale. The present paper illustrates the Delphi process of item generation engaging parents and patients and presents a protocol for the validation of this new co-designed tool in an Italian visually impaired pediatric population. Twenty-three families and five adolescents provided a list of 192 items and assessed their relevance. Items were categorized in 5 areas of adaptive abilities (i.e., table manners, clothing, personal hygiene, orientation and mobility, and socio-affectivity) and into three age ranges based on the patient's age. The final 102-item Vida Scale will be administered to a minimum of 300 visually impaired children together with measures of quality of life and child adjustment to investigate its psychometric properties.

BackgroundJoubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the ‘molar tooth sign’. Over 40 JS-associated genes are known, accounting for two-thirds of cases.MethodsWhile most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known ‘founder variants’ in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in ~550 European patients with JS and compared them with controls (>15 000 Italian plus gnomAD), and with an independent cohort of ~600 JS probands from the USA.ResultsAll variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216c.218G>T) was significantly enriched in American compared with European patients with JS, whileMKS1c.1476T>G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes.Two recurrent variants (MKS1c.1476T>G andKIAA0586c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from aMKS1c.1476T>G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from aKIAA0586c.428delG healthy homozygote.ConclusionThis study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants.

PURPOSE. The purpose of this study was to perform a detailed longitudinal phenotyping and genetic characterization of 32 Italian patients with a nonsyndromic retinal dystrophy and mutations in the CEP290 gene. METHODS. We reviewed the clinical history and examinations of 32 patients with a nonsyndromic retinal dystrophy due to mutations in the CEP290 gene, followed up (mean followup: 5.9 years) at 3 Italian centers. The clinical examinations included: best corrected visual acuity (BCVA), optical coherence tomography (OCT), and full-field electroretinogram (ERG). RESULTS. Patients (mean age = 19.0 ± 3.4 years) had a mean BCVA of 1.73 ± 0.20 logMAR. Longitudinal analysis of BCVA showed a nonsignificant decline. Central retinal thickness (CRT) declined significantly with age at an exponential rate of 1.0%/year (P = 0.001). At disease onset, most patients (19/32; 49.4%) had nystagmus. The absence of nystagmus was significantly associated with better BCVA and more preserved CRT (P < 0.05). ERG showed undetectable responses in most patients (64.0%), whereas reduced scotopic and photopic responses were observed in four patients (16.0%) who had no nystagmus. We identified 35 different variants, among which 12 were novel. Our genotype-phenotype correlation analysis shows a significantly worse BCVA in patients harboring a loss-of-function mutation and the deep-intronic variant c.2991+1655A>G. CONCLUSIONS. Our study highlights a mild phenotype of the disease, characterized by absence of nystagmus, good visual acuity, considerably preserved retinal morphology, and recordable ERG, confirming the wide spectrum of CEP290-related retinal dystrophies. Finally, in our cohort, the deep intronic variant c.2991+1655A>G was associated with a more severe phenotype.

Background Heterozygous mutations in the PACS1 gene have been shown to cause Schuurs-Hoeijmakers syndrome, a rare condition characterized by intellectual disability and peculiar facial dysmorphisms. To date, 52 cases have been reported (49 postnatally and 3 prenatally diagnosed). Case report We describe a child carrying the recurrent PACS1 c.607C>A variant; besides the typical neurodevelopmental and physical features of the condition, he also showed previously unreported cerebellar and ocular findings. Conclusions Our findings expand the clinical and neuroimaging presentation of Schuurs-Hoeijmakers syndrome and confirm the power of "genotype first" approach in patients with syndromic phenotypes. We also suggest a role for PACS1 in influencing cerebellar and ocular development.

Research has shown that the ability to integrate complementary sensory inputs into a unique and coherent percept based on spatiotemporal coincidence can improve perceptual precision, namely multisensory integration. Despite the extensive research on multisensory integration, very little is known about the principal mechanisms responsible for the spatial interaction of multiple sensory stimuli. Furthermore, it is not clear whether the size of spatialized stimulation can affect unisensory and multisensory perception. The present study aims to unravel whether the stimulated area’s increase has a detrimental or beneficial effect on sensory threshold. Sixteen typical adults were asked to discriminate unimodal (visual, auditory, tactile), bimodal (audio-visual, audio-tactile, visuo-tactile) and trimodal (audio-visual-tactile) stimulation produced by one, two, three or four devices positioned on the forearm. Results related to unisensory conditions indicate that the increase of the stimulated area has a detrimental effect on auditory and tactile accuracy and visual reaction times, suggesting that the size of stimulated areas affects these perceptual stimulations. Concerning multisensory stimulation, our findings indicate that integrating auditory and tactile information improves sensory precision only when the stimulation area is augmented to four devices, suggesting that multisensory interaction is occurring for expanded spatial areas.

BackgroundJoubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%.In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies.MethodsWe reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes.ResultsHeterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents.ConclusionHeterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk.

Joubert Syndrome (JS) is a rare inherited neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation (i.e. the molar tooth sign) and variable organ involvement. The aim of the present study was to describe functional limitations and disabilities in a large sample of adult patients with a diagnosis of JS. We administered the International Classification of Functioning (ICF) checklist to thirty-six adult Italian patients with JS or their caregivers through telephone calls. None-to-mild impairment was documented for basic cognitive and mental functions, whereas severe deficit emerged for higher-order skills and language. A mismatch between individuals’ capacity for daily activity and social participation and the actual performance in these fields emerged, suggesting that adults with JS may greatly benefit from external support from the caring environment. Indeed, specific facilitators were highlighted, including communication technologies as well as family members, healthcare professionals and peers support. Mild-to-severe barriers have been identified by adult patients with JS in the domains of services, systems and policies. These findings highlight challenges and barriers for adults with JS in areas of daily functioning that may be improved by investing in rehabilitation care models that embed social support programs and policies into clinical interventions.IMPLICATIONS FOR REHABILITATIONChildren with Joubert Syndrome, a child-onset rare inherited neurodevelopmental condition, are growing up and becoming adults; a life course approach in rehabilitation is needed;There is a substantial lack of information on the long-term adaptive daily functioning of children with a diagnosis of Joubert Syndrome;In this paper, the International Classification of Functioning (ICF) was applied to assess the daily functioning in people with JS;Severe deficits emerged for high-order skills and language, whereas the use of communication technologies and the engagement of family members were highlighted as key facilitators;These findings highlight the need for a change of paradigm in the care model of subjects with JS, with the embedding of social support in rehabilitation programs. Children with Joubert Syndrome, a child-onset rare inherited neurodevelopmental condition, are growing up and becoming adults; a life course approach in rehabilitation is needed; There is a substantial lack of information on the long-term adaptive daily functioning of children with a diagnosis of Joubert Syndrome; In this paper, the International Classification of Functioning (ICF) was applied to assess the daily functioning in people with JS; Severe deficits emerged for high-order skills and language, whereas the use of communication technologies and the engagement of family members were highlighted as key facilitators; These findings highlight the need for a change of paradigm in the care model of subjects with JS, with the embedding of social support in rehabilitation programs.

The aim of the present work is to introduce a novel wearable device suitable to be used to investigate perception in interactive tasks, on individuals with and without sensory disabilities. The system is composed by small units embedded with sensors and actuators that allows emitting different kind of stimuli (light, haptic, sound) and to record the user response, thanks to a capacitive sensor. We validated the system by implementing an interception task in three different sensory modalities: visual, tactile and auditory. Six subjects with normal sight were asked to tap either a static or a moving stimulus generated by 6 units placed on their forearm. Results suggest that the system can effectively provide new insights in characterizing how perception principles vary when perceptual judgement occurs through different senses. This confirms the device potential in contributing to the design of rehabilitation protocols rooted on neuroscientific findings, for people with sensory impairments.

The acquisition of spatial cognition is essential for both everyday functioning (e.g., navigation) and more specific goals (e.g., mathematics), therefore being able to assess and monitor spatial cognition from the first years of life would be essential to predict developmental outcomes and timely intervene whenever spatial development is compromised. Several shreds of evidence have indicated that spatial development can be compromised in the case of development with atypical sensory experience such as blindness. Despite the massive importance of spatial abilities for the development of psychomotor competencies across childhood, only a few standardized and experimental methods have been developed to assess them in visually impaired children. In this review, we will give a short overview of current formal (standardized) and informal (experimental) methods to assess spatial cognition in visually impaired children, demonstrating that very few validated tools have been proposed to date. The main contribution of this current work is to highlight the need of ad hoc studies to create and validate clinical measures to assess spatial cognition in visually impaired individuals and address potential future developments in this area of research.

Introduction Joubert syndrome (JS) is a recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including optic nerve morphologic abnormalities. The function of the visual pathways, including the optic nerve, can be objectively evaluated by visual evoked potential (VEP) recordings. Our work aims to employ VEP to evaluate the neural conduction along the visual pathways in JS patients with or without optic nerve morphologic abnormalities (ONMA). Methods In this observational and prospective study, 18 children with genetic diagnosis of JS (mean age 8.78 ± 5.87 years) and 17 healthy age-similar control subjects (control group, 9.05 ± 6.02 years) were enrolled. Based on presence/absence of ONMA at fundus examination, JS patients were divided into two groups: the JS-A group (eight patients with ONMA) and JS-N group (ten patients without ONMA). Following the ISCEV standards, pattern VEPs were recorded in patients and controls in response to 60’ and 15’ checks to obtain a prevalent activation of large or small axons, respectively. Results Compared to controls, both the JS-A and JS-N groups showed significant abnormalities in 60’ and 15’ VEP implicit time and amplitude. Only in the JS-N group were values of 15’ VEP implicit significantly correlated with the corresponding values of visual acuity. Conclusions Our results suggest that a visual pathways dysfunction (of both large and small axons) detectable by VEP may occur in JS patients regardless of the presence of ONMA. Since clinical trials are envisaged in the near future to address JS-related ocular problems, our results might provide information about the potential usefulness of VEP recordings to assess the efficacy of treatments targeted to improve the visual pathways’ function.

Summary Congenitally blind infants are not only deprived of visual input but also of visual influences on the intact senses. The important role that vision plays in the early development of multisensory spatial perception1, 2, 3, 4, 5, 6, 7 (e.g., in crossmodal calibration8, 9, 10 and in the formation of multisensory spatial representations of the body and the world1,2) raises the possibility that impairments in spatial perception are at the heart of the wide range of difficulties that visually impaired infants show across spatial,8, 9, 10, 11, 12 motor,13, 14, 15, 16, 17 and social domains.8,18,19 But investigations of early development are needed to clarify how visually impaired infants’ spatial hearing and touch support their emerging ability to make sense of their body and the outside world. We compared sighted (S) and severely visually impaired (SVI) infants’ responses to auditory and tactile stimuli presented on their hands. No statistically reliable differences in the direction or latency of responses to auditory stimuli emerged, but significant group differences emerged in responses to tactile and audiotactile stimuli. The visually impaired infants showed attenuated audiotactile spatial integration and interference, weighted more tactile than auditory cues when the two were presented in conflict, and showed a more limited influence of representations of the external layout of the body on tactile spatial perception.20 These findings uncover a distinct phenotype of multisensory spatial perception in early postnatal visual deprivation. Importantly, evidence of audiotactile spatial integration in visually impaired infants, albeit to a lesser degree than in sighted infants, signals the potential of multisensory rehabilitation methods in early development. Video abstract, Highlights • Visually impaired infants have a distinct phenotype of audiotactile perception • Infants with severe visual impairment (SVI) place more weight on tactile locations • SVI infants show attenuated audiotactile spatial integration and interference • SVI infants do not show an influence of body representations on tactile space, Gori et al. show that infants with severe visual impairment have a distinct phenotype of multisensory spatial perception. Compared to sighted infants, they show attenuated audiotactile spatial integration and interference, have a more limited influence of body representations on tactile space, and place a greater weight on tactile than auditory cues.

Vision and touch play a critical role in spatial development, facilitating the acquisition of allocentric and egocentric frames of reference, respectively. Previous works have shown that children’s ability to adopt an allocentric frame of reference might be impaired by the absence of visual experience during growth. In the current work, we investigated whether visual deprivation also impairs the ability to shift from egocentric to allocentric frames of reference in a switching-perspective task performed in the visual and haptic domains. Children with and without visual impairments from 6 to 13 years of age were asked to visually (only sighted children) or haptically (blindfolded sighted children and blind children) explore and reproduce a spatial configuration of coins by assuming either an egocentric perspective or an allocentric perspective. Results indicated that temporary visual deprivation impaired the ability of blindfolded sighted children to switch from egocentric to allocentric perspective more in the haptic domain than in the visual domain. Moreover, results on visually impaired children indicated that blindness did not impair allocentric spatial coding in the haptic domain but rather affected the ability to rely on haptic egocentric cues in the switching-perspective task. Finally, our findings suggested that the total absence of vision might impair the development of an egocentric perspective in case of body midline-crossing targets.

To determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations. Twenty-eight patients harbouring 23 heterozygous pathogenic variants (ten novel) in tubulin genes TUBA1A (n = 10), TUBB2B (n = 8) or TUBB3 (n = 5) were studied by a brain MRI scan performed either on a 1.5 T (n = 10) or 3 T (n = 18) MR scanner with focus on the posterior fossa. Cerebellar anomalies were detected in 24/28 patients (86%). CD was recognised in 19/28 (68%) including cortical cerebellar dysplasia (CCD) in 18/28, either involving only the cerebellar hemispheres (12/28) or associated with vermis dysplasia (6/28). CCD was located only in the right hemisphere in 13/18 (72%), including four TUBB2B-, four TUBB3- and five TUBA1A-mutated patients, while in the other five TUBA1A cases it was located only in the left hemisphere or in both hemispheres. The postero-superior region of the cerebellar hemispheres was most frequently affected. The cerebellar involvement in tubulinopathies shows specific features that may be labelled as ‘tubulin-related CD’. This pattern is unique and differs from other genetic causes of cerebellar dysplasia. • Cortical cerebellar dysplasia without cysts is suggestive of tubulin-related disorder. • Cerebellar dysplasia in tubulinopathies shows specific features labelled as ‘tubulin-related CD’. • Focal and unilateral involvement of cerebellar hemispheres has important implications for counselling.

BackgroundJoubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain–hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25–30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS.MethodsRenal features were investigated in 93 Italian patients, including biochemical tests, ultrasound and 1-deamino-8D-arginine vasopressin test in children with reduced basal urine osmolality. A subset of patients was followed-up over time.ResultsAt last examination, 27 of 93 subjects (29%) presented with CKD, ranging from isolated urinary concentration defect (UCD) to end-stage renal disease. Both normal and pathological urine osmolality levels remained stable over time, even when obtained at very early ages. Follow-up data showed that the probability of developing CKD can be modelled as a function of the urine osmolality value, exceeding 75% for levels ConclusionsWe conclude that the frequency of CKD in JS increases with age and is higher than previously reported. Urine osmolality represents an early sensitive quantitative biomarker of the risk of CKD progression.

It has been shown that the total or partial lack of visual experience is associated with a plastic reorganization at the brain level, more prominent in congenital blind. Cortical thickness (CT) studies, to date involving only adult subjects, showed that only congenital blind have a thicker cortex than age-matched sighted population while late blind do not. This was explained as a deviation from the physiological mechanism of initial neural growth followed by a pruning mechanism that, in congenital blind children, might be reduced by their visual deprivation, thus determining a thicker cortex. Since those studies involved only adults, it is unknown when these changes may appear and whether they are related to impairment degree. To address this question, we compared the CT among 28 children, from 2 to 12 years, with congenital visual impairments of different degree and an age-matched sighted population. Vertex-wise analysis showed that blind children, but not low vision one, had a thicker cortical surface in few clusters located in occipital, superior parietal, anterior-cingular, orbito-frontal, and mesial precentral regions. Our data suggest that the effect of visual impairment on determining thicker cortex is an early phenomenon, is multisystemic, and occurs only when blindness is almost complete.

ObjectiveTo estimate the prevalence of Joubert syndrome (JS) in Italy applying standards of descriptive epidemiology and to provide a molecular characterization of the described patient cohort.MethodsWe enrolled all patients with a neuroradiologically confirmed diagnosis of JS who resided in Italy in 2018 and calculated age and sex prevalence, assuming a Poisson distribution. We also investigated the correlation between proband chronological age and age at diagnosis and performed next-generation sequencing (NGS) analysis on probands' DNA when available.ResultsWe identified 284 patients with JS: the overall, female- and male-specific population-based prevalence rates were 0.47 (95% confidence interval [CI] 0.41–0.53), 0.41 (95% CI 0.32–0.49), and 0.53 (95% CI 0.45–0.61) per 100,000 population, respectively. When we considered only patients in the age range from 0 to 19 years, the corresponding population-based prevalence rates rose to 1.7 (95% CI 1.49–1.97), 1.62 (95% CI 1.31–1.99), and 1.80 (95% CI 1.49–2.18) per 100,000 population. NGS analysis allowed identifying the genetic cause in 131 of 219 screened probands. Age at diagnosis was available for 223 probands, with a mean of 6.67 ± 8.10 years, and showed a statistically significant linear relationship with chronological age (r2 = 0.79; p < 0.001).ConclusionsWe estimated for the first time the age and sex prevalence of JS in Italy and investigated the patients’ genetic profile. The obtained population-based prevalence rate was ≈10 times higher than that available in literature for children population.

Background Parent-child interaction is essential to promote adaptive emotional, cognitive, and social development. The majority of previous research on parent-child interaction is largely dependent on face-to-face exchanges that require the interactive partners to visually recognize reciprocal communicative bids. Therefore, previous findings in the field can only partially apply to the early interactive patterns occurring between visually impaired infants and their parents. The present study was aimed to systematically review the available evidence on parent-child interaction in the context of developmental visual impairment. Methods Fourteen papers were finally selected after literature search on PubMed and Scopus. Data synthesis was focused on three core topics: visually impaired children’s contribution to the interaction, parental caregiving behaviors with visually impaired children, and the association between parents’ behaviors and the developmental outcomes of children with visual impairment. Results Visually impaired children may exhibit reduced reactivity to maternal stimuli and less-than-optimal levels of interactive initiations in social exchanges. Parents of children with visual impairment may use more descriptive communicative acts and greater directiveness compared to mothers of sighted counterparts. Specific caregiving behaviors (e.g., responsiveness and goal setting) of parents of children with visual impairment may significantly support language and socio-emotional development as well as sensorimotor integration. Discussion Children with visual impairment may be less responsive and they may produce less clear communicative bids while interacting with their parents. Their parents may face specific challenges while engaging with them and they may become increasingly directive and intrusive. Nonetheless, even in the presence of visual impairment, the quality of parental caregiving behaviors appears to play a potential preventive role in the face of children’s socio-emotional and cognitive outcomes. These results suggest that early interventions focused on parent-child interactions are especially needed in this population.

The original version of this article, published on 4 July 2017, unfortunately contained a mistake. The following correction has therefore been made in the original: The first name of the author Raffaella Cusmai was rendered incorrectly and has now been corrected.

FOXG1-related syndrome is a developmental encephalopathy with a high phenotypic variability. A movement disorder presenting at onset is one of the main features, along with microcephaly and severe psychomotor delay without regression. Specific brain MRI findings facilitate the diagnosis. We report three cases of FOXG1-related syndrome, focusing on clinical onset, brain MRI and evolution over time in order to identify common features despite the three different underlying genotypes (14q12 deletion including the FOXG1 gene, FOXG1 intragenic mutation, 14q12 deletion including PRKD1 and a region regulating FOXG1 expression). In conclusion, we stress the importance of considering genetic syndromes in the differential diagnosis of early-onset movement disorders.

Joubert syndrome (JS) is an inherited autosomal recessive or X-lined disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features. It is estimated that retinal dystrophy is present in association with the typical neurological findings in about one-third of the patients. The aim of this study is to better characterize the macular region in JS patients with and without retinal dystrophy. We describe six individuals affected by JS as demonstrated by the presence of the typical “molar tooth sign” on MRI. The presence of retinal dystrophy was assessed by fundus examination and electrophysiology by means of full-field electroretinogram (ERG) and visual evoked potentials (VEP) at five spatial frequencies (300–15 min of arc). The macular region was examined with spectral domain optical coherence tomography (SD-OCT). All the exams were performed in awake conditions. All the patients underwent next-generation-sequencing analysis of known JS genes. Pathogenic biallelic variants in either the INPP5E gene or the AHI1 gene were detected in two pairs of siblings, all positive for retinal dystrophy. Genetic testing yielded no results in the remaining two patients, one with bilateral coloboma and retinal dystrophy and the other with normal fundus appearance. Decimal best-corrected visual acuity was between 0.1 and 1.0. In the two pairs of siblings, SD-OCT revealed a posterior staphyloma centred on the fovea, in one case associated with cystoid macular oedema. Macular morphology was just slightly altered in the fifth patient and completely normal in the last patient. Refractive error was between + 2.50 diopter sphere (DS) and − 8 DS and − 4 diopter cylinder ax 45°. ERG waves were markedly lower than the normal limits in both scotopic and photopic components in the two pairs of siblings and in the fifth subject, with VEP P100 latencies and amplitudes delayed and reduced in all spatial frequencies. ERG and VEP were within normal limits in the last patient. To our knowledge, macular staphyloma has not been described before in JS. Further work is warranted to assess the true prevalence of staphyloma in JS and its connection to retinal dystrophy.

Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients. Electronic supplementary material The online version of this article (doi:10.1007/s00439-014-1508-3) contains supplementary material, which is available to authorized users.