Rare Disorder Research Articles

Polymyxin-B induced bartter-like syndrome: an unusual adverse effect

Introduction and Importance: Bartter syndrome is a rare autosomal recessive disorder affecting renal tubular function, leading to electrolyte and volume homeostasis disturbances. It can also manifest as Bartter-like syndrome, a rare side effect of certain medications. Polymyxin-B, used to treat multidrug-resistant infections, is infrequently associated with BLS, making early recognition crucial to prevent severe electrolyte imbalances. Case Presentation: A 73-year-old female with coronary artery disease, COPD, hyperlipidemia, and other comorbidities presented with fever, respiratory distress, and hypoxia on mechanical ventilation. Initial labs showed leukocytosis, anemia, and normal potassium. Despite broad-spectrum antibiotics, sputum cultures revealed pandrug-resistant Acinetobacter baumannii, sensitive only to Polymyxin-B. After six days of Polymyxin-B, the patient developed fever, hypotension, hypokalemia, hypomagnesemia, and polyuria. Urine studies indicated increased potassium excretion. A diagnosis of Bartter like syndrome was made. Polymyxin-B was discontinued, and the patient’s electrolytes normalized, resolving the polyuria. She was discharged with daily potassium and magnesium supplements. Clinical Discussion: Bartter-like syndrome can result from Polymyxin-B-induced tubular dysfunction, characterized by hypokalemia and hypomagnesemia. Close electrolyte monitoring is essential for patients receiving this antibiotic, particularly in those with complex medical conditions. Early recognition allowed for timely discontinuation of Polymyxin-B, which rapidly reversed the electrolyte disturbances. Conclusion: This case underscores the importance of recognizing Polymyxin-B-induced Bartter-like syndrome. Clinicians should be vigilant for electrolyte disturbances in patients undergoing treatment with Polymyxin-B, ensuring timely interventions to mitigate adverse outcomes.

Intermittent Explosive Disorder

Intermittent explosive disorder is characterized by recurrent episodes of inability to resist aggressive impulses, resulting in damage to other people or other people's property. In the history of DSM, it first appeared as 'isolated explosive disorder' in DSM-III. However, with some changes in the diagnostic criteria, it is included under the title of 'destructive, impulse control and conduct disorders' in DSM-5. Although previous studies have shown it is a rare disorder, recent epidemiological studies suggest it may be more common than thought. For this reason, it is essential to master the clinical features and learn the treatment methods in order to recognize people with this disorder and apply the appropriate treatment.

Short and longterm outcome of minimally invasive therapy of median arcuate ligament syndrome.

Median arcuate ligament syndrome (MALS) is a rare disorder caused by compression of the celiac artery (CA) by the median arcuate ligament (MAL). Common symptoms include postprandial abdominal pain, diarrhea, and weight loss. While laparoscopic MAL division has long been considered the procedure of choice, robotic-assisted procedures have been increasingly used since their introduction. Aim of this study was to evaluate peri- and postoperative outcomes after minimally invasive MAL release. A retrospective analysis of patients undergoing minimally invasive MAL release at the Department of Surgery, Charité - Universitätsmedizin Berlin, between 2014 and 2023 was performed. 20 patients met the inclusion criteria and underwent either laparoscopic (n = 3) or robotic (n = 17) MAL release. Most common preoperative symptoms were postprandial abdominal pain (90%), weight loss (45%), diarrhea (30%), and nausea (25%). Comparing laparoscopic and robotic surgery, neither the median duration of surgery (minutes: 98 (90-290) vs. 125 (80-254); p = 0.765), the median length of hospital stay (days: 4 (3-4) vs. 5 (3-6); p = 0.179) and intraoperative blood loss (< 50ml in both groups, p = 1.0) showed significant differences. Peak systolic velocity in the CA was significantly reduced postoperatively (cm/s: 320 (200-765) vs. 167 (100-500), p < 0.001). Postoperatively, 17 (85%) patients reported symptom improvement, while 4 (20%) patients had no symptom relief at last follow-up. In 3 cases, follow-up imaging showed evidence of respiratory-related CA stenosis. Despite being complex and challenging procedures, laparoscopic and robotic-assisted MAL release are safe procedures with low risk of postoperative complications and good longterm outcomes.

Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. Symptoms range from cerebral demyelination (cALD) to adrenal insufficiency and slowly progressive myeloneuropathy. cALD is fatal if not treated with hematopoietic cell transplantation in the early stages of the disease course. This can be achieved through cascade testing or newborn screening (NBS). Due to the lack of predictive measures of disease trajectory, patients are monitored with frequent MRI scans and hormone testing to ensure timely intervention. With this study, we wanted to explore how the diagnosis of ALD, before the development of cALD, and the follow-up program affected patients and their parents. Using semi-structured interviews, we interviewed seven parents of children with ALD aged 3–11 and four patients with ALD aged 18–25. Because NBS for ALD has not been implemented in Denmark, the patients were identified through either cascade testing or after having presented with adrenal insufficiency. We generated five themes: (I) ALD patients maintained mental resilience despite diagnosis and surveillance; (II) patients’ concerns matured with age and centered around situations that confronted them with their patient status; (III) parents of children with ALD had both short-term and long-term worries for their children’s health; (IV) parents took on a huge psychological burden; and (V) due to its rarity, the diagnosis of ALD evoked a sense of isolation and disease-related loneliness. Overall, we found a large discrepancy in the experiences reported by parents and patients. Despite the small sample size, we identified patterns that suggest that while the early diagnosis took a significant psychological toll on the parents, patients lived relatively carefree lives despite their ALD diagnosis.

Long-Term Lung Function and Pseudomonas aeruginosa Infection in Genotyped Primary Ciliary Dyskinesia.

Rationale: Primary ciliary dyskinesia is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease, known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in primary ciliary dyskinesia grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa. Methods: In this retrospective, observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated FEV1 z-score trends and compared them at ages 10, 25, and 50 years, while Generalized Estimating Equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Measurements and Main Results: We included 127 genotyped subjects, 6,691 spirometries and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early onset and sustained decline in lung function, while DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures were on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa. Conclusion: Long-term lung function in primary ciliary dyskinesia follows discrete genotype specific profiles and appear independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC40 as variants associated with early onset severe lung function impairment persisting in the long term.

A qualitative study on the field experience of genetic counseling in Korea.

In Korea, genetic counseling services began with the opening of genetic clinics in the early 1990s; in recent years, demand for these services has increased. However, genetic counseling is not an officially recognized healthcare service under the Korean national health insurance system; further, its certification is not recognized as a medical qualification. To clarify the role and significance of genetic counselors, this study examined their field experiences. To this end, we conducted focus group interviews with 11 certified genetic counselors, six advanced practice nurses, and four regular nurses. The interviews were transcribed verbatim and examined using thematic analysis. We found that even though Korea did not recognize their roles, the participants met their responsibilities and primary duties. In addition, they faced challenges during counseling due to a lack of formal education in genetics and genomics. Moreover, they encountered dilemmas related to the legal and ethical aspects of decision support for family testing or prenatal diagnosis due to the complexity of rare genetic disorders. However, they attempted to acquire the specialized knowledge needed to support patients with rare genetic disorders and their families, gradually developing practical experience and specialized knowledge. Therefore, it is necessary to develop manuals, establish systems, and improve working environments to provide high-quality and specialized genetic counseling. Additionally, there is a need for national support, such as establishing set wages for genetic counselors, developing a national qualification certification system, and securing dedicated personnel.

Reversal of Denervation Changes in Infraspinatus Muscle After Operative Management of Paralabral Cysts: An MRI-Based Study.

Paralabral cysts at the spinoglenoid notch are rare disorders that can potentially lead to compressive suprascapular neuropathy. Given their infrequency, a standard treatment protocol has not yet been established. This study aimed to assess changes in the infraspinatus muscle using magnetic resonance imaging (MRI) and to compare the outcomes of 2 different surgical methods. It was hypothesized that surgical intervention could alleviate compressive neuropathy, with comparable outcomes between the 2 surgical approaches. Cohort study; Level of evidence, 3. This retrospective review encompassed 43 patients undergoing arthroscopic labral repair for a paralabral cyst at the spinoglenoid notch, with cyst decompression (27 patients; labral repair with cyst decompression [LRCD] group) or without cyst decompression (16 patients; labral repair only [LRO] group). Preoperative MRI focused on evaluating the condition of the infraspinatus and teres minor muscles. Electromyography (EMG) was conducted on 36 patients (21 in LRCD and 15 in LRO) to assess suprascapular nerve function. Postoperative evaluations were performed in 35 patients at postoperative 1 year, excluding those lost to follow-up. Postoperative MRI findings (24 patients in LRCD and 11 patients in LRO) and functional outcome scores including recovery of external rotation power were compared with preoperative status in both groups. Preoperative MRI revealed denervation changes or atrophy of the infraspinatus in 26 of the 43 patients (60.4%). Among the 36 patients who underwent preoperative EMG, 21 patients (58.3%; 13 patients in LRCD and 8 patients in LRO) showed evidence of suprascapular neuropathy. A discrepancy between EMG and MRI findings was noted in 10 patients, with 5 patients showing suprascapular neuropathy according to EMG despite normal muscle status on MRI scans, and the remaining 5 vice versa. Notable atrophy of the infraspinatus was seen in 6 patients and teres minor hypertrophy in 5 patients, all of whom exhibited concurrent infraspinatus atrophy. Postoperatively, cyst disappearance was observed in all cases in both LRCD (24 patients) and LRO (11 patients) groups. Denervation changes in the infraspinatus were resolved in all patients. In patients with infraspinatus atrophy, some improvement was noted. Teres minor hypertrophy persisted in 2 of 4 patients. Improvements were similar in both groups (all P > .05). External rotation power improved postoperatively in both groups (from 39.1 ± 18.6 to 50.6 ± 17.7 N in LRCD, P < .001; from 45.1 ± 16.0 to 54.2 ± 10.7 N in LRO, P = .025). Both LRCD and LRO surgical approaches appear to be effective for paralabral cysts at the spinoglenoid notch. Suprascapular neuropathy can be successfully addressed by both methods. However, conditions with severe infraspinatus atrophy and teres minor hypertrophy warrant further investigation in larger series.

Epidermolytic Hyperkeratosis Type 1 with a New Heterozygous Mutation in KRT1 Gene: A Case Report

Background: Epidermolytic hyperkeratosis (EHK) formerly known as bullous ichthyosiform erythroderma, is a rare autosomal dominant inheritance condition with a prevalence ranging from 1:200,000 to 1:300,000. The underlying etiology of which is a mutation in the genes responsible for keratin proteins synthesis, primarily in KRT1 and KRT10 genes, cataloged under OMIM number 113800. Clinicopathological presentations include blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescence, characterized by the hallmark features of generalized dry skin, scaling, hyperkeratosis, and frequently associated with erythroderma. EHK may present with or without palmoplantar keratoderma involvement, depending on the keratin gene variant. Case report: A 24-year-old male of Arab descent was born with diffuse skin hyperkeratotic plates featuring erythematous fissures, covering his entire body, resembling a collodion baby. His birth was full-term via cesarean section without complications, although he later developed developmental dysplasia of the hip. By the time he started primary school, he began experiencing severe thickening of the skin around his joints, reducing flexibility and leading to contractures and significant disfigurement. He is undergoing treatment with acitretin. Genetic testing using Next-Generation Sequencing (NGS) was performed to identify the responsible gene, revealing a novel heterozygous variant in the KRT1 gene (OMIM 139350), while no variant was detected in the KRT10 gene. Conclusion: EHK type 1 manifests with a new heterozygous variant in the KRT1 gene. This rare disorder, associated with variant in genes related to keratin production such as KRT1 and KRT10, results in distinctive skin features present from birth, as well as joint problems and fungal foot infections. Genetic testing has confirmed the presence of a variant in the KRT1 gene.

A Novel Pathogenic Mutation in WNK1 Gene Causing HSAN Type II in Three Siblings.

Hereditary sensory and autonomic neuropathy (HSAN) is a rare genetic disorder that primarily affects the peripheral nervous system, leading to a progressive loss of the ability to perceive pain, temperature, and touch. This condition can result in severe complications, including injuries and infections due to the inability to feel pain. HSAN is classified into nine types, with types I and VII exhibiting autosomal dominant inheritance, while the others follow an autosomal recessive pattern. In this study, we examined three affected brothers of Turkish Azeri descent, aged 20, 23, and 25 years. They presented symptoms such as a lack of temperature and pain sensation, frequent wounds and infections, self-harm, and hyperkeratosis. To identify the genetic cause of their condition, whole-exome sequencing (WES) was performed, followed by Sanger sequencing to confirm the findings. The results revealed a homozygous likely pathogenic nonsense mutation, c.2971C > T (p.Arg991Ter), in exon 9 of the WNK1 gene. This mutation results in the truncation of three isoforms of the WNK1 protein, which are essential for pain perception. This discovery enhances our understanding of HSAN and highlights the importance of genetic testing for accurate diagnosis and future screening.

CLCN2-related leukoencephalopathy with novel compound heterozygous variants followed with magnetic resonance imaging over 17 years: a case report

BackgroundCLCN2-related leukoencephalopathy (CC2L) is a rare autosomal recessive disorder caused by biallelic variants of CLCN2, which encodes chloride channel 2. Although CC2L is associated with distinct radiological features, it presents with a wide range of clinical features.Case presentationA 34-year-old woman presented to our hospital with a sudden onset of vertigo with headache. The patient reported intermittent headaches and tingling in both arms since the age of 31 years. On the first visit, the patient was alert and neurologically intact, except for slight hyperreflexia of the limbs without laterality. Head magnetic resonance imaging (MRI) showed high-intensity signals on axial T2-weighted fluid-attenuated inversion recovery and diffusion-weighted images bilaterally in the posterior limbs of the internal capsules, cerebral peduncles, superior and middle cerebellar peduncles, decussation of superior cerebellar peduncles, and central tegmental tract. All the patient’s symptoms were resolved or eased following supportive care. The patient stopped attending our hospital at the age of 46 years. At 51 years of age, the patient revisited our hospital because of the recurrence of vertigo, headache, and nausea. She did not present with any abnormalities by neurological examination. Head MRI showed widespread high-intensity signals similar to those 17 years ago. Genetic testing revealed compound heterozygous variants in CLCN2 (NM_004366.6): a novel variant c.1828 C > T, p.(Arg 610*) from her father and c.61dup, p.(Leu21Profs*27) from her mother. The patient was finally diagnosed with CC2L. She received supportive treatment, which made her symptoms manageable.ConclusionsThis is a detailed report of a patient with adult-onset CC2L who was successfully diagnosed and followed up with head MRI. This report provides new insights into CC2L and highlights its persistent, distinct, and stable characteristics observed in head MRI over one decade and the difficulty in forming a diagnosis without MRI when patients have minimal and common symptoms, such as in the present case.

Gluteric aciduria ( type-I) Presenting as Bilateral Subdural Hygroma- A Case Report with Literature Review

Glutaric aciduria type 1 (GA-1) is an autosomal recessive rare neurometabolic disorder caused by absent or deficient activity of glutaryl- CoA dehydrogenase. Patient with gluteric aciduria are more likely to develop collection in the subdural space secondary to cerebral atrophy and expansion of CSF spaces. A 1 year and 10 months toddler presented with increased head circumference since birth and generalized seizure for last few days. Neuroimaging showed bilateral subdural collection of CSF intensity. Bilateral subdural peritoneal shunt was inserted. With early diagnosis and adequate treatment , the majority of children with gluteric aciduria type-I are able to live normal. However treatment for gluteric aciduria type-I must be continued for life to avoid lifethreatening complications Bang. J Neurosurgery 2024; 13(2): 162-164

Molecular and Clinical Heterogeneity in Hungarian Patients with Treacher Collins Syndrome—Identification of Two Novel Mutations by Next-Generation Sequencing

Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder with variable penetrance and high genetic and phenotypic heterogeneity. It is caused by pathogenic variants in the TCOF1, POLR1D, POLR1C, and POLR1B genes, and its major characteristic features are malar and mandibular hypoplasia, downward slanting of the palpebral fissures, and conductive hearing loss. In this study, five patients (two males and three females, age range from 2 to 29 years) with TCS were tested by Next-Generation Sequencing (NGS)-based sequencing and clinically characterized. Genetic analyses detected two deletions and one insertion in the TCOF1 gene and one missense variant in the POLR1D gene. Two novel mutations, c.1371_1372insT (p.Lys458*) in the TCOF1 gene and c.295 G&gt;C (p.Gly99Arg) in the POLR1D gene, were identified. Moreover, two already known mutations, c.4369_4373del (p.Lys1457Glufs*12) and c.2103_2106del (p.Ser701Argfs*9) in the TCOF1 gene, were detected. The novel TCOF1 c.1371_1372insT mutation was associated with mild craniofacial manifestations and very rare symptoms of TCS, i.e., developmental delay and moderate intellectual disability. Although incomplete penetrance is a known phenomenon in TCS, surprisingly, the majority of our patients inherited the disease-causing variants from an asymptomatic mother. The unique feature of our study is the observation of causative mutation transmission between asymptomatic family members. Our results expanded the clinical and mutational spectrum of TCS and further confirmed the inter- and intra-familial variability of this disorder.

Pregnancy and delivery after functional hemispherectomy for Rasmussen’s encephalitis: a case report

BackgroundRasmussen’s encephalitis (RE) is a rare neurologic disorder characterized by progressive seizures and unilateral cerebral atrophy with onset during childhood and unknown etiology. When medical therapy appears refractory, surgical disconnection of the affected hemisphere is indicated. Quality of life after functional hemispherectomy is largely good, affected females may therefore pursue pregnancy. However, data on pregnancy and delivery in RE post hemispherectomy is extremely rare.Case presentationWe present the case of a patient with left functional hemispherectomy for RE at the age of seven, who experienced two successful pregnancies. In both pregnancies, her post-surgical symptoms including right-sided spasticity, cephalgia, dizziness, and impairment of vision and speech deteriorated but improved to pre-pregnancy level after delivery. Neurologic sequelae post-hemispherectomy overlapped with clinical signs of preeclampsia and required close diagnostic surveillance during both pregnancies.ConclusionThere are no data on the interaction between RE, hemispherectomy and pregnancy, making maternal and fetal risk assessment difficult. Due to the complexity of the condition and symptoms, management of RE in pregnancy remains highly challenging and requires an interdisciplinary approach. This is the first case description of two successful pregnancies in a woman with RE and status post-hemispherectomy. Further evidence is urgently required to improve counseling and management of affected women.

A Rare Cause of Recurring Lung Infection: Moebius Syndrome

Moebius syndrome is a rare congenital disorder characterized by bilateral paralysis of the VIth and VIIth cranial nerves, leading to facial diplegia and bilateral paralysis of ocular abduction, often associated with orofacial anomalies. This work reports a case collected at the pediatric infectious diseases and pneumo-allergology department of the Children's Hospital of Rabat, of a 9-month-old male infant, 6th of a family of six, of non-consanguineous parents, with a delay in psychomotor acquisitions. The examination shows facial dysmorphism with hypertelorism, epicanthus and right facial paralysis. Since birth, he has had swallowing disorders causing repeated respiratory infections, hence his hospitalization in our training. The etiopathogenesis of this disease remains controversial, with a great clinical heterogeneity whose observed signs are mainly due to the involvement of the VIth and VIIth cranial pairs, mainly resulting in various orofacial and ocular anomalies. The treatment remains symptomatic based on a multidisciplinary approach. The aim of this observation is to identify the particularities of this syndrome with a view to early diagnosis and effective management.

Neimann-Pick Diseases: Beyond Lipid Accumulation – Genetic, Diagnostics, and Therapeutic Strategies

Rare genetic disorders are the group of disorders/diseases that occur in such a low count that they are not considered much active market for therapeutics unless encouraged by appropriate incentives and support. They are too rare to be fully investigated and managed by health professionals. Genetic disorders are caused by change in genes and are often serious and complex. Around the world, most affected individuals are found to be children. They can be progressive and might get worse as children grow older. Niemann-Pick diseases (NPD) is one such group of rare genetic diseases that are characterized by unwanted and abnormal accumulation of lipids within the cells. In this review, we discuss the history, genetic basis, clinical manifestations and diagnostic approaches for NPD. We further discuss the pathophysiology of accumulation of lipids and their impact on cellular functions and organ systems and various management strategies.Keywords: Rare disease; Genetic mutation; Lipid metabolism; Cholesterol trafficking; Neurological abnormalities

Optimizing the anesthetic care of patients with aromatic l-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder that results in a lack of the monoamine neurotransmitters dopamine, serotonin, norepinephrine, and epinephrine. Patients present with a wide spectrum of symptoms, including motor and autonomic dysfunction, hypotonia, and developmental delay, often before the age of one. Until recently, treatment options were limited to symptom control, but the recent approval of the first gene therapy for AADC deficiency in Europe and the UK has provided an alternative to treating symptoms for this disease. Eladocagene exuparvovec is a one-time gene therapy, administered bilaterally to the putamen by magnetic resonance imaging-guided stereotactic neurosurgery. While administration of the gene therapy itself is minimally invasive, the anesthetic management of patients with AADC deficiency is challenging due to the absence of sympathetic regulation secondary to the lack of adrenergic neurotransmitters. Optimal anesthetic management requires an understanding of the complex and heterogeneous nature of the disease. Hemodynamic instability, temperature dysregulation, and hypoglycemia are of primary concern, but there are also challenges regarding intravenous access and airway management. A thorough preoperative assessment is essential and should be guided by the patient's history. Advanced planning is necessary regarding the timing of the procedure schedule and operative plan; meticulous preparation, simulation for the operating room, as well as communication with all perioperative staff members, are crucial. Intraoperatively, utmost care must be taken to protect the skin, maintain body temperature, and to prepare for inotropic and/or glycemic support as needed. Postoperative intensive care management is necessary for consideration of postoperative extubation and provision of supportive care. With careful planning, preparation, and vigilance, patients with AADC deficiency can safely undergo anesthesia.

Psychological conditions of caregivers of adult subjects with Prader-Willi syndrome

BackgroundPrader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder. Individuals with PWS face a range of cognitive, behavioral, and emotional challenges that require comprehensive and lifelong care, posing significant demands on their caregivers. The study is not only aimed to assess the psychological conditions of caregivers of adult subjects with PWS focusing on psychological distress and coping, but also to shed light on a crucial yet often overlooked aspect of healthcare. This study aims to compare the psychological well-being of individuals with PWS and their caregivers, providing valuable insights that can potentially improve the quality of care for these individuals. The sample recruited at the Division of Auxology, IRCCS Istituto Auxologico Italiano, was composed of 30 adult subjects with PWS (11 men and 19 women; mean age ± SD: 36.4 ± 10.31 years; mean Body Mass Index (BMI): 35.7 ± 8.92: kg/m2) and their caregivers (10 men and 20 women). To assess the psychological condition of caregivers, the Italian-validated versions of the Depression Anxiety and Stress Scale (DASS-21) and the Coping Orientation to the Problems Experiences (COPE) were used, while to assess the psychological well-being of individuals with PWS and their caregivers, the Italian validated version of the Psychological General Well-Being Index (PGWBI) was used.ResultsDepression (p < 0.001), Stress (p = 0.050), and Total score (p = 0.009) of DASS 21 were higher in the caregivers of subjects with PWS than in the general population. PGWBI scores of caregivers were significantly lower than in individuals with PWS in Positive Well-being (p < 0.001), General Health (p = 0.006), Vitality (p = 0.004), and the total score (p = 0.006). The depression subscale of PGWBI was higher in caregivers than in subjects with PWS. Correlations between the subscales of COPE and the total score of PGWBI in caregivers revealed that the Avoidance subscale of COPE had a negative significant correlation with the total score of PGWBI (p = 0.003).ConclusionsOur results highlighted several critical insights into the profound emotional and psychological challenges faced by the caregivers of individuals with PWS.

Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain.

Transcription factor 4 (TCF4) has been implicated in a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. Mutations or deletions in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare neurodevelopmental disorder. A detailed understanding of its spatial expression across the developing brain is necessary for comprehending TCF4 biology and, by extension, to develop effective treatments for TCF4-associated disorders. However, most current knowledge is derived from mouse models, which are invaluable for preclinical studies but may not fully capture the complexities of human neuropsychiatric phenotypes. This study compared TCF4 expression in the developing mouse brain to its regional and cellular expression patterns in normal prenatal, neonatal, and young adult rhesus macaque brains, a species more relevant to human neurodevelopment. While the general developmental expression of TCF4 is largely conserved between macaques and mice, we saw several interspecies differences. Most notably, a distinct layered pattern of TCF4 expression was clear in the developing macaque neocortex but largely absent in the mouse brain. High TCF4 expression was seen in the inner dentate gyrus of adult mice but not in macaques. Conversely, TCF4 expression was higher in the adult macaque striatum compared to the mouse striatum. Further research is needed to show the significance of these interspecies differences. Still, they underscore the importance of integrating rodent and primate studies to comprehensively understand TCF4 function and its implications for human disorders. Moreover, the primate-specific expression patterns of TCF4 will inform genetic and other therapeutic strategies to treat TCF4-associated disorders.

Phenotypic Variability in Camurati–Engelmann Disease: A Case Report of a Family with the c.653G&gt;A Pathogenic Variant in the TGFB1 Gene

Camurati–Engelmann Disease (CED), or Progressive Diaphyseal Dysplasia, is a rare autosomal dominant disorder caused by heterozygous mutations in the TGFB1 Gene, essential for bone regeneration. This study examines the genotype–phenotype relationship in a family diagnosed with CED, specifically focusing on a missense variant (c.653G&gt;A, p.Arg218Cys). The family comprised a mother and her two children, all of whom were found to carry the same disease-causing variant. The second child exhibited severe symptoms by age six, including progressive weakness and joint pain, leading to wheelchair dependency. The mother displayed milder symptoms with preserved independence. The firstborn son, initially asymptomatic, developed gait abnormalities and pain during adolescence. Clinical evaluations revealed characteristic hyperostosis of long bones, with significant variability in symptom onset and severity among family members, potentially indicative of genetic anticipation. This case underscores the importance of genetic testing and interdisciplinary management in CED, as traditional treatments, including corticosteroids and NSAIDs, often yield limited efficacy and notable side effects. Our findings contribute to the understanding of CED’s pathophysiology and highlight the necessity for tailored therapeutic approaches. The identification of the common TGFB1 variant in this family reinforces the critical role of TGFB1 in bone metabolism and suggests avenues for further research into targeted therapies. Such reports enhance awareness and provide valuable insights for healthcare professionals managing rare genetic disorders.

Mendelian Susceptibility to Mycobacterial Disease with Signal Peptide Peptidase-like 2A (SPPL2A) Deficiency: A Case Report

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by immunodeficiency, leading to increased susceptibility to mycobacterial infections. Studies have identified several genes that are associated with MSMD in the interferon-gamma/interleukin (IL)-12/IL-23 signaling pathway. One of these genes is signal peptide peptidase-like 2A (SPPL2A), which is very rare, and defects in this gene have been reported only in 3 patients with MSMD. This case report presents the rare SPPL2A deficiency with an abnormal presentation, which adds to the limited number of these genetic defects. This report presents the case of a 1-year-old boy who developed Bacillus Calmette-Guerin infection (BCGitis), lymphadenopathy, and an arm abscess that required surgical drainage following BCG vaccination. The patient had hypogammaglobulinemia, normal B-cell counts, normal CD4 counts, low CD8 counts, and SPPL2A deficiency, which is related to MSMD. The patient received a second line of anti-tuberculosis agents. SPPL2A deficiency is associated with MSMD and can cause severe BCGitis and disruption of immunoglobulin production.