Brugada syndrome (BrS) is an inherited arrhythmic disorder characterized by ST-segment elevation (STE) on leads V1-V3 of electrocardiograms (ECG), and associated with an increased risk of sudden cardiac death (SCD). Although a high prevalence has been reported in some Southeast Asian countries, systematic epidemiological data from mainland China are currently lacking. This retrospective cross-sectional study enrolled 117,050 hospitalized patients at a tertiary hospital in Southern China between 2023 and 2024. Standard 12-lead electrocardiograms (ECG) were recorded from participants. Suspected BrS cases received either pharmacological challenge with propafenone or had right precordial leads placed in high intercostal spaces, followed by ambulatory ECG monitoring. BrS diagnosis was confirmed according to the 2013 h/EHRA/APHRS expert consensus criteria. A total of 244 BrS cases were confirmed, yielding a prevalence of 208.5 per 100,000 persons (95
Abstract Background Nephrocalcinosis and cystinuria are two distinct kidney disorders. Nephrocalcinosis is the abnormal, generalised deposition of calcium salts, primarily calcium phosphate or calcium oxalate, within the kidney's parenchyma, and has multiple causes including metabolic disorders, monogenic kidney diseases and medications. Cystinuria, resulting from pathogenic variants in SLC3A1 or SLC7A9 which impair amino acid reabsorption in the proximal convoluted tubule leads to cystinuria and predisposes to cystine stone formation. Case Here we describe a patient with recurrent episodes of renal colic from the age of 17 years and the formation of calcium containing kidney stones as well as medullary nephrocalcinosis. Biochemical investigations revealed evidence of mild hypophosphatemia and cystinuria. Genetic screening identified a heterozygous likely pathogenic variant in SLC34A3 consistent with the kidney stones and nephrocalcinosis as well as a heterozygous likely pathogenic variant in SLC7A9 consistent with the cystinuria phenotype. Genetic testing of available relatives identified several additional family members carrying one or more of these variants, enabling diagnosis, early risk stratification and counselling. Conclusions This case highlights the rare co-occurrence of medullary nephrocalcinosis and cystinuria secondary to two heterozygous genetic variants. It demonstrates the role of genetic screening in patients with kidney stone disease phenotypes and the correlation of clinical and biochemical phenotypes with genetic findings. Identification of these variants facilitated personalised management and screening of at-risk relatives.
Abstract Rare diseases (RDs) affect millions across the Community of Portuguese-Speaking Countries (CPLP), yet fragmented governance, uneven diagnostic capacity, and limited data interoperability constrain timely diagnosis and access to care. Anchored in the first-ever World Health Assembly (WHA) resolution on RDs, this position paper outlines a pragmatic Lusophone agenda that couples standards-based data infrastructure with regulatory alignment, workforce development, and cross-border collaboration. We conducted a narrative, policy-oriented synthesis drawing on scientific literature, policy and institutional documents, international RD initiatives, and existing collaborative efforts among CPLP countries. We focus on Orphanet RD codes (ORPHAcodes) for disease coding, the Human Phenotype Ontology (HPO) for structured phenotyping, Global Alliance for Genomics and Health (GA4GH) Phenopackets for computable case exchange, and governance models for secure, federated data sharing. We highlight operational lessons from European Reference Networks and tele-expertise platforms, and we foreground equity and privacy safeguards—dynamic consent and federated analytics—as key design considerations for low-connectivity contexts. Building on the experiences of Brazil and Portugal, as well as emerging African initiatives, we propose a sequenced roadmap for national registries, virtual multidisciplinary boards, and capacity-building pipelines aligned with global standards. Implementation metrics include time to confirmed diagnosis, proportion of molecular confirmations, and geographic equity in access. The recommendations are intended as a propositional roadmap requiring national validation, local adaptation, and sustained governance to reduce inequities in RD care.
Mirror movement disorder (MMD) is a rare neurological condition characterized by involuntary movements on one side of the body that mirror intentional movements on the opposite side. Understanding the pathophysiology of this condition requires a comprehensive assessment of corticospinal tract integrity through multimodal approaches. This mini review includes our previously published case of a patient with MMD, and reviews recent advances reported in the literature. As MMD is a complex neurological disease, it needs a detailed evaluation. We have evaluated our case using whole-exome sequencing, computed tomography (CT), diffusion tensor imaging (DTI), and transcranial magnetic stimulation (TMS) to elucidate the underlying mechanisms. Whole-exome sequencing analysis prioritized variants in neurologically expressed genes using a predefined logarithm of odds (LOD) score threshold; variants of uncertain significance were further assessed through in silico predictive modeling tools (SIFT, PolyPhen-2, and CADD) to determine likely pathogenicity. Furthermore, recent studies in the field expand our findings by contextualizing them within the broader literature on axon guidance molecules, genetic underpinnings, and emerging therapeutic strategies. The multidisciplinary approach can provide insight into the complex interplay between structural abnormalities and functional motor output in this rare disease, while highlighting the critical role of the corticospinal fiber decussation in normal bimanual coordination.
Progressive Encephalopathy with Brain Edema and/or Leukoencephalopathy-1 (PEBEL-1) is a rare, rapidly progressive, and often fatal infantile neurometabolic disorder caused by pathogenic variants in the NAXE gene. Loss of NAXE impairs the NAD(P)HX repair pathway, leading to toxic accumulation of damaged nicotinamide nucleotide metabolites. The clinical course typically shows recurrent, fever-triggered neurological decompensation, mimicking combined metabolic and mitochondrial dysfunction. The condition progresses quickly to severe neuroregression and death. This report describes an early-onset, lethal case of NAXE-related encephalopathy exhibiting the classical fluctuating course and rapid decline. A 5-month-old male infant, born to consanguineous parents with a history of multiple unexplained infant deaths, presented with fever, acute encephalopathy, and seizures. Initial metabolic evaluation suggested a neurometabolic disorder. Whole-exome sequencing identified a homozygous NAXE variant (c.401_402del, p.Phe134TrpfsTer13) consistent with PEBEL-1. Despite intensive management, including a mitochondrial cocktail, corticosteroids, and intravenous immunoglobulin, the child experienced progressive neuroregression, choreoathetosis, hypotonia, and intractable seizures. His condition continued to deteriorate, culminating in death secondary to aspiration. The clinical course illustrates the characteristic severity and high lethality of NAXE deficiency. This case highlights the diagnostic complexity of NAXE-related infantile encephalopathy, a disorder with overlapping metabolic and mitochondrial features and a rapidly progressive, treatment-refractory course. The underlying defect in NAD(P)HX repair renders conventional metabolic and immunomodulatory therapies largely ineffective. Early genetic testing is crucial, especially in consanguineous families with recurrent neonatal or infant deaths. Although emerging therapies such as NAD⁺ precursors (e.g., niacin) or pyridoxine supplementation are under investigation, their clinical efficacy remains uncertain. NAXE variant should be considered in infants presenting with episodic encephalopathy, movement disorder, and unexplained neuroregression.
Split notochord syndrome is an extremely rare and controversial congenital anomaly considered part of the broader spectrum of complex spinal dysraphism and neurenteric developmental disorders. It results from abnormal embryological separation of the endoderm and ectoderm, leading to a range of vertebral, spinal cord, and potential enteric malformations. Due to significant overlap with other dysraphic conditions, diagnosis is primarily radiological and often challenging. We report a case of a 10-day-old female neonate presenting with a dorsal lumbosacral swelling noted since birth, delivered at home to a mother with no antenatal care. Physical examination revealed a midline, skin-covered spinal mass without cerebrospinal fluid leakage. MRI of the spine, performed using a low-field (0.5 Tesla) system, demonstrated a midline vertebral defect, widening and segmentation abnormalities of posterior elements, and duplication of the spinal cord, with additional features suggestive of severe spinal dysraphism within the neurenteric spectrum. The diagnosis was based solely on imaging findings without surgical or histopathological confirmation. The constellation of findings was most consistent with probable split notochord syndrome within the neurenteric spectrum. The neonate received supportive management but deteriorated and died after seven days of hospitalization. This case highlights a severe form of spinal dysraphism within the split notochord/neurenteric spectrum diagnosed on MRI in a resource-limited setting. It underscores the importance of early antenatal surveillance and postnatal imaging for prompt recognition of complex congenital spinal anomalies. MRI remains the key diagnostic modality for defining the extent of disease and guiding management, although overlap between entities within this spectrum may limit strict diagnostic classification.
Pemphigus foliaceus (PF) typically presents with superficial blistering but may occasionally manifest in atypical non-blistering forms that mimic other inflammatory dermatoses. We report a diagnostically challenging case of PF presenting with widespread psoriasiform plaques without clinically evident blistering. A 71-year-old woman with a background of eczema presented with widespread erythematous, scaly plaques clinically resembling psoriasis. Skin punch biopsy was performed with histopathological examination and direct immunofluorescence testing. Histopathology demonstrated psoriasiform epidermal hyperplasia with parakeratotic crusting and foci of possible superficial acantholysis. Direct immunofluorescence revealed intercellular IgG and C3 deposition; although the immunofluorescence pattern was considered more compatible with pemphigus vulgaris, the histological findings were suggestive of pemphigus foliaceus. The final diagnosis of PF was established through clinical-pathological correlation. Following treatment of secondary Staphylococcus aureus infection and initiation of systemic corticosteroids with azathioprine and adjunctive doxycycline, the patient achieved marked clinical improvement with resolution of plaques within six weeks. This case highlights that PF may present without clinically apparent blistering and can closely mimic psoriasiform dermatoses. Histopathological examination with immunopathological correlation is essential for accurate diagnosis. Early recognition and prompt systemic immunosuppressive therapy can lead to excellent clinical outcomes.
SELENON -related congentital myopathy is a rare autosomal recessive congenital myopathy characterized by early-onset axial weakness, spinal rigidity, and progressive respiratory insufficiency. Although cases have been reported in several Middle Eastern populations, this condition has not previously been described in Lebanon. The purpose of this study is to report the first Lebanese cases of SELENON-related congenital myopathy and to highlight the role of exome sequencing in establishing a precise diagnosis in a previously unreported geographic setting. We conducted a clinical and genetic evaluation of affected individuals from three unrelated Lebanese families presenting with axial hypotonia, spinal stiffness, and respiratory involvement suggestive of an underlying myopathy. Detailed clinical assessments were performed, followed by exome sequencing to identify potential pathogenic variants. Genetic findings were interpreted in correlation with clinical phenotypes. Exome sequencing identified pathogenic or likely pathogenic variants in the SELENON gene in all three families, confirming the diagnosis of SELENON-related congenital myopathy. Clinically, patients demonstrated early axial weakness, progressive spinal rigidity, and varying degrees of respiratory compromise. A history of consanguinity was noted in the families, consistent with the autosomal recessive inheritance pattern. The use of exome sequencing was instrumental in achieving a definitive diagnosis, particularly given the nonspecific clinical presentation and the rarity of the condition in Lebanon. This report represents the first documented cases of SELENON-related congenital myopathy in Lebanese patients. Our findings underscore the clinical heterogeneity of the disorder and emphasize the added value of exome sequencing in diagnosing rare neuromuscular diseases, especially in regions where such conditions are unfamiliar or underrecognized.
Abstract Introduction Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder characterized by progressive neurodegeneration. Its marked clinical variability complicates genotype–phenotype correlations, making the reporting of novel variants important. The present report describes a case of NPC associated with novel compound heterozygous (CH) variants in the NPC1 gene with intrafamilial phenotypic heterogeneity. Case presentation A 20-month-old girl presented with delayed walking. She had a history of prolonged neonatal jaundice. Family history was notable for a male sibling who had been genetically diagnosed with NPC and died in infancy. Physical examination revealed hepatosplenomegaly. Laboratory investigations revealed microcytic anemia, thrombocytopenia, elevated aspartate aminotransferase, and hypertriglyceridemia. Abdominal ultrasonography demonstrated hepatosplenomegaly. Whole exome sequencing identified novel variants of uncertain significance (VUS) in the NPC1 gene (c.3422T > A (p. Val1141Asp) and c.2870G > C (p. Cys957Ser) in trans configuration) with predicted deleterious effects. The same variants were previously detected in a deceased sibling, supporting segregation within the family. A probable diagnosis of Niemann–Pick disease type C (NPC) was made based on clinical features, family history, and identification of compound heterozygous NPC1 variants in trans configuration. Definitive confirmation was limited by the absence of NPC-specific biomarker testing. The patient is currently under regular follow-up, and genetic counseling has been provided to the parents. Literature review In a review of 10 NPC cases, six patients (60.0%) were male, with ages ranged from the neonatal period to 67 years. Clinical manifestations varied according to the age at onset of neurological symptoms. Genetic analysis identified CH variants in the NPC1 gene, including novel variants in 20% of cases. Conclusions The identification of novel NPC1 variants may expand the mutational spectrum of NPC. More importantly, this case illustrates the classical intrafamilial phenotypic discordance in NPC between a perinatal rapidly fatal form in one sibling and an early infantile neurological form in the propositus — a clinically significant pattern that remains underrecognized.
The clinical translation of CRISPR- Cas9 therapeutics requires rigorous and biologically grounded evaluation of genome editing fidelity that extends beyond conventional measures of on-target efficiency and canonical off-target detection. Existing fidelity assessment strategies often capture limited aspects of editing outcomes and do not fully account for context-dependent biochemical, epigenetic, and cellular heterogeneity that can influence therapeutic safety and efficacy. This review focuses on analytical and translational frameworks for CRISPR fidelity assessment, with emphasis on the strengths and limitations of current bioanalytical platforms. Recent advances integrating orthogonal technologies including digital droplet PCR, genome-wide off-target mapping approaches (e.g., CIRCLE-seq and GUIDE-seq), and single-cell proteogenomic profiling enable more comprehensive characterization of editing outcomes across molecular and functional dimensions. Applications in edited T cells targeting immune checkpoints and in hematopoietic stem cell correction models illustrate how multi-layered analyses can reveal context-dependent variability and previously undetected off-target effects. Emerging approaches, including integrative scoring frameworks and AI-assisted analytical models, are discussed in an exploratory context, with emphasis on current limitations, validation requirements, and challenges in standardization. In addition, ongoing efforts toward minimally invasive monitoring strategies are considered with respect to their potential, as well as their current constraints. Despite significant progress, major challenges remain in assay harmonization, cross-platform comparability, and translation to clinically actionable frameworks. Accordingly, CRISPR fidelity is best understood as a multi-dimensional biological phenotype that requires careful, context-specific evaluation. This perspective provides a balanced foundation for advancing genome editing toward safer and more reliable therapeutic applications.
Abstract Congenital eyelid eversion is an uncommon, benign condition characterised by the outward turning of the eyelids, predominantly affecting the upper eyelids and often associated with systemic or syndromic conditions. We present a rare case of isolated bilateral congenital eyelid eversion in a term male neonate, detected immediately after birth. There were no signs of syndromic features or systemic abnormalities. Importantly, a family history was noted, with an older male sibling who had a similar condition at birth, indicating a possible genetic predisposition. Progressive clinical improvement of the ectropion was observed with conservative treatment, and by the sixth day after birth, it had completely resolved. This case illustrates the potential for a positive outcome with conservative treatment for isolated congenital eyelid eversion and emphasises the importance of recognising familial patterns in its clinical evaluation.
Acute promyelocytic leukemia (APL) is highly curable with targeted therapy combining all-trans retinoic acid (ATRA) and arsenic trioxide, yet the microgranular variant (M3v) frequently mimics monocytic leukemia and may delay diagnosis. Although FLT3 internal tandem duplications are common cooperating lesions, concurrent FLT3 tyrosine kinase domain (FLT3-TKD) mutations and MYC amplification remain rarely reported in APL. We report a genomically defined case of M3v-APL harboring both FLT3-TKD (D835Y) and high-level MYC amplification (≥ 8 copies/cell). A 35-year-old woman presenting with pancytopenia, disseminated intravascular coagulation, and prominent schistocytosis suggestive of secondary microangiopathic changes underwent immediate bone marrow examination, flow cytometry, FISH, RT-PCR, and targeted next-generation sequencing using a 54-gene myeloid panel. Diagnostic studies confirmed PML::RARA fusion (bcr-3 isoform), FLT3-TKD D835Y (variant allele frequency 42
Abstract Rare neurological and neuropsychiatric syndromes, although individually uncommon, collectively contribute to misdiagnosis, avoidable investigations, and occasional preventable harm. Many of these conditions sit at the interface of neurology and psychiatry and are vulnerable to diagnostic overshadowing, in which clinically unfamiliar presentations are dismissed as functional or psychiatric. This narrative review examines six clinically significant entities that exemplify this problem: Beauty Parlor Stroke Syndrome (BPSS), Alice in Wonderland Syndrome (AIWS), Alien Hand Syndrome (AHS) and Alien Limb Phenomenon (ALP), Exploding Head Syndrome (EHS), Cotard’s Delusion (CD), and the syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL). These conditions were selected because each is uncommon, each is reproducibly misclassified in routine practice (typically as a psychiatric, functional, or benign positional disorder), and each has a defined neurological substrate with implications for management. We provide a narrative synthesis of published literature, drawing on case series, cohort studies, narrative reviews, and consensus criteria such as the International Classification of Headache Disorders, 3rd edition (ICHD-3) for HaNDL. BPSS is discussed as a mechanical cause of vertebrobasilar ischaemia, classically following cervical hyperextension at a salon basin, in which symptoms are commonly attributed initially to benign positional vertigo or anxiety. AIWS is described as a perceptual disorder characterised by dysmetropsia and altered body schema, most often associated with migraine in adults and with viral infection (particularly Epstein–Barr virus) in children; reported lifetime prevalence in adult migraineurs varies between studies in the approximate range of 16–19%, with higher rates in those with migraine with aura. The distinction between AHS, typically of acute callosal or frontal medial origin, and ALP, more typically associated with parietal dysfunction in corticobasal syndrome, is clarified. EHS is presented as a benign sensory parasomnia that mimics serious intracranial events. Cotard’s delusion is described as a nihilistic delusion most often arising in severe depression with psychotic features and carrying a significant risk of self-neglect and suicide. HaNDL is framed according to ICHD-3 criteria as an important stroke and encephalitis mimic. We discuss cross-cutting diagnostic pitfalls, summarise recommended investigations and management, and outline the limitations of the current evidence base, which is dominated by case reports and small case series. We also briefly consider the limited but emerging role of digital symptom search and artificial-intelligence tools as adjuncts to clinical reasoning, not as substitutes for it.
Abstract Background Unilateral absence of the pulmonary artery (UAPA) is a rare congenital anomaly that may remain clinically silent until adulthood. Pregnancy and the postpartum period may unmask previously compensated congenital heart disease and pulmonary vascular disease, creating diagnostic challenges when patients present with heart failure symptoms. Case report A 22-year-old woman presented three months postpartum with rapidly progressive dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and generalized edema after an uncomplicated vaginal delivery. Peripartum cardiomyopathy was initially suspected; however, cyanosis, digital clubbing, elevated jugular venous pressure, right ventricular heave, and loud pulmonary component of the second heart sound suggested chronic right-sided pressure overload. Echocardiography showed right atrial and ventricular dilatation, reduced right ventricular function, severe tricuspid regurgitation, severe pulmonary hypertension, bidirectional shunting across a ventricular septal defect and patent ductus arteriosus, and non-visualization of the right pulmonary artery. Computed tomography confirmed unilateral absence of the right pulmonary artery, a large subaortic ventricular septal defect extending into the membranous septum, persistent patent ductus arteriosus, and systemic collateral supply to the right lung. These findings were most consistent with complex cyanotic congenital heart disease with severe pulmonary hypertension and clinically suspected Eisenmenger-like physiology unmasked postpartum. She improved with diuresis, oxygen therapy, anticoagulation, and pulmonary vasodilator therapy. Conclusion Postpartum heart failure with cyanosis, clubbing, or predominant right-sided findings should prompt evaluation for previously unrecognized congenital heart disease and pulmonary vascular disease. Right pulmonary artery agenesis may be an important associated finding, but pulmonary hypertension should be interpreted according to the complete congenital anatomy and shunt physiology.
Abstract Introduction The diagnosis of Hansen’s disease (HD) relies on the detection of the cardinal signs of leprosy. Clinical examination for nerve thickening carries significant inter observer variability, which emphasizes the significance of non-invasive investigations like nerve ultrasound. Objectives To describe the sonological characteristics of peripheral nerve involvement in Hansen’s disease. Methods A descriptive study spanning 1year was conducted among 37 consecutive patients with clinical features suggestive of leprosy who attended the Dermatology OPD in Government T.D. Medical College, Alappuzha (a tertiary care medical college in Kerala, India). After taking informed consent, history, complete dermatological examination including sensory, motor systems and peripheral nerves were done. Ultrasonography of bilateral ulnar nerves, median nerves, common peroneal nerves and posterior tibial nerves of all patients were done, assessing their cross sectional area, echo reflectivity and vascularity. All data were entered in Microsoft Excel sheet and analysed using SPSS 20.0 statistical software. Results The mean age was 39.9 years. Male to female ratio was 3.1:1. 21.6% were immigrants. 86.5% belonged to multibacillary type and 13.5% were paucibacillary. The most common type of leprosy was borderline tuberculoid. 3 pure neuritic leprosy cases were identified. 40.5% had lepra reactions, 80% of which being type 1 reaction. Initial presentation was in the form of lepra reaction in 6 patients. 83.7% patients had peripheral nerve enlargement at the time of presentation. 81.1% had impaired nerve sensation, 40.54% patients had motor function impairment, 43% patients had grade 2 disability and 1 patient had cranial nerve involvement. Out of the total 296 nerves imaged, 29 nerves which were not thickened clinically were found to be thickened while 7 nerves which were clinically identified as thickened, were found non-thickened on USG. On comparing clinical and sonological thickening of peripheral nerves, significant p value was obtained for all except left posterior tibial nerve. Hypoechogenicity was noted in 77 nerves. Increased vascularity was seen in only 7 nerves, out of which 4 were in type 1 reaction and 3 were in type 2 reaction. Conclusion Our study sheds light on the different clinical and sonological dimensions of leprosy. As peripheral nerve thickening is a cardinal feature of leprosy, clinical examination alone may end up in missing this crucial diagnosis. Ultrasonography being a newer, non-invasive and easily available investigation proves useful to study the changes in nerves even among patients without palpably enlarged nerves or neurological signs.
Abstract We present a case of developmental auditory–visual synesthesia and its neurophysiological investigation in a female patient in her late teens. She began experiencing persistent positive visual phenomena at age 14, followed by the development of auditory–visual synesthesia. Neurophysiological assessment was conducted using EEG testing. In this study, we focus on the resting EEG and its relationship to colored hearing synesthesia. During music performance, visual EEG inspection revealed a sequential frequency acceleration shifting from the left temporal regions (auditory cortex) to the left centroparietal regions at the onset of color perception, supporting the two-stage hyperbinding model of synesthesia.
Abstract Aim This systematic review aims to explore the psychosocial impact and mental health challenges of childeren and adoloscents with rare diseases (RDs) and their families. It examines their daily challenges, emotional distress, coping mechanisms, and resilience strategies while identifying systemic gaps in care and support. Methods The review adhered to PRISMA guidelines, employing a comprehensive search of databases; Google Scholar, PubMed and PsycINFO. Studies were selected based on predefined criteria and appraised for quality using the Mixed Methods Appraisal Tool (MMAT). Both qualitative and mixed method studies were included, focusing on mental health challenges, caregiver stress, coping mechanisms, and resilience strategies. Results Children and adolescents with RDs face significant emotional distress, including anxiety, depression, and a diminished quality of life, which are exacerbated by physical limitations, frequent hospitalizations, and social exclusion. Meanwhile, their primary caregivers endure profound emotional and financial burdens, compounded by the demands of advocacy roles and navigating fragmented care systems. Although families adopt various coping mechanisms, such as peer support and creative outlets like art therapy, systemic gaps in psychosocial support and access to interdisciplinary care remain prevalent. Conclusion The findings underscore the need for integrated, family-centred care models that address the multifaceted challenges of living with RDs. By fostering holistic medical, psychological, and social support systems, these models can enhance resilience, reduce the psychosocial burden, and improve the overall quality of life for children with RDs and their care.
Abstract Purpose Individuals with 22q11.2 deletion syndrome (22q11.2DS) show a wide range of somatic features. The syndrome also leads to increased prevalence of neuropsychiatric disorders including schizophrenia, attention deficit hyperactivity disorder and early-onset Parkinson’s disease, presumably mediated by alterations in dopaminergic neurotransmission. Diagnostic biomarkers already in clinical use for Parkinson’s disease are increased size of the echogenic area of the substantia nigra (SN) and reduced olfactory function. The aim of the study was to investigate these two characteristics in patients with 22q11.2DS but without Parkinson’s disease. Methods Olfactory function (sensitivity and discrimination) was assessed with the Sniffin’ Sticks test. The maximal size of the echogenic area of the substantia nigra (SNmax in mm2) in transcranial sonography was evaluated by two raters blinded to subjects’ clinical status. Findings of patients with 22q11.2DS and controls were compared in analyses of covariance. Results The sample for assessment of olfactory function comprised N = 60 patients (N = 37 males, m = 17.3 ± 8.8 years) and N = 60 controls. The sample for assessment of SN echogenicity comprised N = 50 patients (N = 30 males, m = 16.02 ± 7.8 years) and N = 50 controls. The group with 22q11.2DS showed impaired olfactory sensitivity (F1,105 = 36.109, p < .001, partial eta2 = .256) and discrimination (F1,109 = 51.248, p < .001, partial eta2 = .320) compared to controls. No significant group differences could be observed with regard to the SNmax (p = 0.167). Conclusions In this young sample previous findings demonstrating reduced olfactory function in 22q11.2DS were replicated, whereas no significant changes in echogenicity of SN were detected.
Abstract Purpose Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder frequently associated with sensorineural hearing loss (SNHL). Due to mitochondrial dysfunction, cochlear structures, especially the stria vascularis and outer hair cells, are susceptible to damage, causing progressive hearing impairment. Cochlear implantation (CI) offers rehabilitative potential, yet unique perioperative challenges related to anesthetic sensitivity and metabolic instability require tailored management strategies. Limited evidence exists regarding CI outcomes specifically in MELAS patients. This systematic review critically evaluates existing literature on CI efficacy, audiological outcomes, and perioperative considerations in MELAS. Methods A comprehensive systematic review following PRISMA guidelines was conducted. Databases including PubMed, Embase, Web of Science, and Scopus were searched for relevant studies reporting outcomes of CI in MELAS patients. Two independent reviewers performed article screening, data extraction, and risk-of-bias assessment. Results From 292 retrieved studies, 8 studies (n = 10 patients) were included. Audiological outcomes consistently showed substantial improvement in speech perception tests post-CI. Standardized assessments demonstrated enhanced sentence and word recognition, alongside improved auditory-evoked potentials (ABR, MLR). Patients reported improvement in social engagement and communication. Surgical interventions were successful despite unique perioperative challenges related to MELAS pathology, including anesthesia complications and metabolic crises. However, existing studies primarily consisted of individual case reports, limiting generalizability. Conclusion Cochlear implantation is an effective rehabilitative option for patients with MELAS syndrome and severe-to-profound sensorineural hearing loss, improving speech perception and communication. Audiological outcomes and electrophysiological measures support its role in restoring auditory function in this unique population. However, given the risks of metabolic decompensation, anesthetic sensitivity, and perioperative electrolyte disturbances in MELAS, careful planning of anesthesia and surgical protocols is critical to patient safety.
