Further defining the molecular spectrum and long-term follow-up of 17 patients with Dyggve-Melchior-Clausen and Smith-McCort dysplasia type 2.

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus. In this study, we investigated 17 affected individuals (8 males, 9 females) from 10 unrelated consanguineous families, 10 diagnosed with DMC and seven with SMC type 2. The mean age at diagnosis was 9.61 ± 9.72 years, ranging from 20 months to 34 years, and the average height at diagnosis was 92.85 ± 15.50 cm. All patients exhibited variable degrees of short trunk with a barrel chest, protruding abdomen, hyperlordosis, and decreased joint mobility. A total of nine different biallelic variants were identified, with six being located in the DYM gene and the remaining three detected in RAB33B. Notably, five variants were classified as novel, four in the DYM gene and one in the RAB33B gene. This study aims to comprehensively assess clinical, radiological, and molecular findings along with the long-term follow-up findings in 17 patients with DMC and SMC type 2. Our results suggest that clinical symptoms of the disorder typically appear from infancy to early childhood. The central notches of the vertebral bodies were identified as early as 20 months and tended to become rectangular, particularly around 15 years of age. Pseudoepiphysis was observed in five patients; we believe this finding should be taken into consideration when evaluating hand radiographs in clinical assessments. Furthermore, our research contributes to an enhanced understanding of clinical and molecular aspects in these rare "skeletal golgipathies," expanding the mutational spectrum and offering insights into long-term disease outcomes.

Review of patients with achondroplasia: a single-center's experience with follow-up and associated morbidities.

Achondroplasia (ACH; MIM #100,800), caused by a heterozygous gain of function pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3; MIM*134,934), is the most prevalent and most readily identifiable cause of disproportionate short stature that is compatible with life. In addition, individuals with achondroplasia face significant medical, functional, and psychosocial challenges throughout their lives. This study assessed associated morbidities in patients with achondroplasia at a single center in Turkey. In this study, the clinical findings and associated morbidities of a group of patients with achondroplasia (n = 68) with clinical multidisciplinary follow-up at a single center between the years 2005-2023 are evaluated retrospectively. A total of 68 patients, 30 male (44.1%) and 38 female (55.9%), were evaluated. In the majority (84.2%) of patients, shortness of extremities was detected in the prenatal period at an average of 28.7 gestational weeks (± 3.6 SDS) with the aid of ultrasonography. More than half (n = 34/63, 54%) of the patients had a father of advanced paternal age (≥ 35 years). Among the complications, respiratory system manifestations, including obstructive sleep apnea (70%), ear-nose-throat manifestations including adenoid hypertrophy (56.6%) and otitis media (54.7%), neurological manifestations due to foramen magnum stenosis (53.2%), and skeletal manifestations including scoliosis (28.8%), are represented among the most common. The mortality rate was 7.3% (n = 5/68).Conclusion: This study not only represents the first retrospective analysis of the associated morbidities of patients with achondroplasia from a single center in Turkey but also will provide a reference point for future studies.

Enhancing systematic reviews in orthodontics: a comparative examination of GPT-3.5 and GPT-4 for generating PICO-based queries with tailored prompts and configurations.

OBJECTIVES: The rapid advancement of Large Language Models (LLMs) has prompted an exploration of their efficacy in generating PICO-based (Patient, Intervention, Comparison, Outcome) queries, especially in the field of orthodontics. This study aimed to assess the usability of Large Language Models (LLMs), in aiding systematic review processes, with a specific focus on comparing the performance of ChatGPT 3.5 and ChatGPT 4 using a specialized prompt tailored for orthodontics. MATERIALS/METHODS: Five databases were perused to curate a sample of 77 systematic reviews and meta-analyses published between 2016 and 2021. Utilizing prompt engineering techniques, the LLMs were directed to formulate PICO questions, Boolean queries, and relevant keywords. The outputs were subsequently evaluated for accuracy and consistency by independent researchers using three-point and six-point Likert scales. Furthermore, the PICO records of 41 studies, which were compatible with the PROSPERO records, were compared with the responses provided by the models. RESULTS: ChatGPT 3.5 and 4 showcased a consistent ability to craft PICO-based queries. Statistically significant differences in accuracy were observed in specific categories, with GPT-4 often outperforming GPT-3.5. LIMITATIONS: The study's test set might not encapsulate the full range of LLM application scenarios. Emphasis on specific question types may also not reflect the complete capabilities of the models. CONCLUSIONS/IMPLICATIONS: Both ChatGPT 3.5 and 4 can be pivotal tools for generating PICO-driven queries in orthodontics when optimally configured. However, the precision required in medical research necessitates a judicious and critical evaluation of LLM-generated outputs, advocating for a circumspect integration into scientific investigations.

Early diagnostic clues of mucolipidosis type II: Significance of radiological findings.

Mucolipidosis type-II (ML-II) is an ultra-rare disorder caused by deficiency of N-acetylglucosaminyl-1-phosphotransferase enzyme due to biallelic pathogenic variants in GNPTAB gene. There are a few known about the natural history of ML-II. In this study, we presented the natural course of 24 patients diagnosed with ML-II. Mean age at diagnosis was 9.3 ± 5.7 months. All patients had coarse face, developmental delay, and hypotonia. The mean survival time was 3.01 ± 1.4 years. The oldest patient was 6.5 years old. Twelve patients died due to lung infection and respiratory failure. We observed early and significant radiological findings of ML-II were different from typical dysostosis multiplex such as femoral cloaking, rickets-like changes, and talocalcaneal stippling. These are significant findings observed in the fetal or newborn period which is considered to be highly characteristic of ML-II and disappears in the first year. Cloaking, rickets-like changes, and stippling were not observed in patients older than three months of age and this suggests that these findings disappear within the first year. These radiological features can be used as important clues for diagnosis. We detected eight different pathogenic variants in GNPTAB gene, three of them were novel.

Clinical Evaluation of Pediatric Patients with Hereditary Angioedema.

Hereditary angioedema is a rare, potentially life-threatening disease. There is a lack of data describing the clinical course of hereditary angioedema (HAE) in children. We aimed to evaluate the clinical characteristics of pediatric patients with hereditary angioedema: The age of disease onset, age at diagnosis, the frequency of angioedema attacks, the total number of attacks before diagnosis, the regions where angioedema attacks were observed, accompanying abdominal pain, and serum levels of C4 and C1 esterase inhibitor were obtained and recorded. In addition, the results of SERPING1 (C1INH) gene sequence analysis of the patients in this group were also collected from medical records and recorded. While none of the patients reported a skin rash as a symptom of attack, there was formication observed in the region of angioedema in 46.9% (n = 15) of the patients and pruritus in 6.2% (n = 2) of the patients. At disease onset, the complaints of the patients regarding location of edema were on the hands of 32.3% (n = 10), on the feet of 9.7% (n = 3), on the faces of 25.7% (n = 8), and abdominal attacks in 32.3% of the patients (n = 10). Four different variants, one of which was novel, were detected in the SERPING1 gene in eight different families. The results of this study suggest that hereditary angioedema is diagnosed only when the patient requests examination following recurrent angioedema. Severe laryngeal edema attacks in patients without a diagnosis of HAE are fatal at a higher rate than attacks in patients with a diagnosis. Thus, awareness of the symptoms of HAE is necessary, and correct diagnosis is essential to proper treatment.

Elastography findings in acne scar patients who were treated with microneedling.

BACKGROUND: Acne scar (AS) is a frequent sequela in patients with acne. In addition to advanced treatment methods, microneedling (MN) is still used as an effective option in the treatment of AS. However, similar to most diseases in dermatology, there is no objective tool to determine the severity of AS and to evaluate the treatment outcome. OBJECTIVES: In the current study, we aimed to evaluate skin elasticity in AS patients who have undergone MN therapy. Furthermore, other purposes were to determine the relationships between the history of isotretinoin use, demographic data, and changes in skin elasticity. METHODS: In order to evaluate the skin elasticity of 20 patients with AS, shear wave elastography (SWE) was performed before and after MN treatment. The physician's clinical assessment was evaluated with quantitative AS severity scale. In order to show that SWE is a consistent method, three repeated measurements were performed on 24 healthy participants. RESULTS: A significant increase was found between the shear-wave velocity (SWV) values that were measured baseline and after treatment in the patient group (P = 0.033). In the control group, there was no significant difference between the three repeated measurements (P > 0.05). A statistically significant decrease was also detected in the AS severity scores (P < 0.005). CONCLUSIONS: In AS patients who underwent MN treatment, a significant increase was found in skin elasticity compared to the baseline. We argued that SWE is a method that can be useful to evaluate skin elasticity before and after similar cosmetic procedures and dermatological diseases.

EXTL3-Associated Immunoskeletal Dysplasia with Neurodevelopmental Abnormalities: A Lethal Phenotype.

Background: Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA) caused by Exostosin-Like Glycosyltransferase 3 (EXTL3) biallelic mutations is a very rare syndrome with only 16 cases reported in the literature. Skeletal dysplasia, neurodevelopmental delay, immunodeficiency, liver, and kidney cysts are the most common findings of this syndrome. Case Presentation: Here, we report on a patient who exhibited a lethal phenotype with clinical characteristics of this syndrome and had a homozygous pathogenic mutation in EXTL3 gene. Conclusions: ISDNA should be kept in mind in the differential diagnosis of patients presenting with neuro-immuno-skeletal dysplasia phenotype.

Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand abnormal calcification type: Further expanding the mutational spectrum and dental findings of three new patients.

Genetic skeletal disorders are clinically and genetically heterogeneous group of disorders that affect the normal development, growth, and maintenance of the human skeleton. Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (SMED-SL/AC; MIM# 271665) is a rare autosomal recessive genetic skeletal disorder characterized by distinctive facial features, disproportionate short stature, vertebral, metaphyseal, and epiphyseal abnormalities. This unique phenotype is caused by biallelic loss-of-function variants in Discoidin domain receptor 2 gene (DDR2, MIM# 191311). To date, only 10 pathogenic variants (six missense, two nonsense, one deletion, and one splice site) in DDR2 have been reported in patients with SMED-SL/AC. Dental anomalies related to skeletal dysplasia can include various abnormalities in the number, shape, and position of teeth in the jaw, as well as enamel hypoplasia and dentinogenesis imperfecta. Although abnormal dentition has previously been reported, orodental findings were described in only six patients with SMED-SL/AC. This study aimed to define the clinical, dental, radiological, and molecular findings of three new SMED-SL/AC patients from three unrelated families. Three DDR2 variants, two of which were novel, were detected with the aid of Sanger sequencing. Interestingly, one of the patients was diagnosed with Wilson's disease (WD) during the follow-up, a co-occurrence that has never been reported in patients with SMED-SL/AC so far.

Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report.

BACKGROUND: Sphingosine phosphate lyase insufficiency syndrome (SPLIS) caused by inactivating mutations in the human SGPL1 gene results in congenital nephrotic syndrome, adrenal insufficiency, ichthyosis, immunodeficiency, and a wide range of pathological neurological features. We present a novel mutation in the SGPL1 gene causing hypocalcemia, primary adrenal insufficiency (PAI), nephrotic syndrome, subclinical hypothyroidism, lymphopenia, ptosis, and pathologic neuroimaging findings. CASE: A Turkish male infant presented with bruising at 2 months of age and was diagnosed with hypocalcemia, PAI, and subclinical hypothyroidism. At the age of 15 months, he was admitted to the hospital with ptosis. Other systemic manifestations included persistent lymphopenia and nephrotic syndrome. Magnetic resonance imaging (MRI) of the brain and orbit demonstrated asymmetric contrast enhancement in the left cavernosal sinus, orbital apex, and thinning at the bilateral optic nerve. Whole exome sequencing (WES) revealed a homozygous c.1432C > G (p.Gln478Glu) variant in the SGPL1 gene (NM_003901.4), which has not previously been reported in the literature. CONCLUSIONS: Novel mutations in SGPL1 are still being identified. This case reminded us that SPLIS should not be considered for patients with nephrotic syndrome alone. Still, PAI may also include patients with neurological disorders, hypocalcemia, and pathological neuroimaging findings such as thinning at the bilateral optic nerve.

White Blood Cell/Mean Platelet Volume Ratio as a Predictor of Long-Term Outcomes but Not Coronary Artery Disease Severity in Non-ST Elevation Myocardial Infarction Patients.

Background White blood cell count (WBC) and mean platelet volume (MPV) have been shown to be hematologic parameters of prognostic significance in acute coronary syndrome. We sought to determine the relationship between the WBC/MPV ratio (WMR), coronary artery disease (CAD) complexity, and long-term clinical outcomes in patients with non-ST elevation myocardial infarction (NSTEMI). Hypothesis WMR has a relationship with the complexity of CAD and long-term clinical outcomes in NSTEMI patients. Methods A total of 289 NSTEMI patients who underwent coronary angiography were divided into two groups according to the median WMR (>970 or ≤970). CAD complexity was assessed with the SYNTAX score. Results The WMR was not associated with the synergy between percutaneous coronary intervention (PCI) with Taxus and cardiac surgery (SYNTAX) score on multivariate linear regression analysis (ß=0.08, 95% CI = -0.76-2.21, p = 0.14). However, it was of prognostic significance on Kaplan-Meier survival analysis in overall patients (log-rank p = 0.03) and in patients with a SYNTAX Score <22 (log-rank p = 0.01). Follow-up data showed that major adverse cardiac events (MACE) (p = 0.02), death (p < 0.001), non-fatal MI (p = 0.03), ischemia-driven revascularization (p = 0.03), and heart failure (p = 0.04) were more frequent in the high WMR group. After adjustment for age, sex, eGFR, troponin levels, and the Global Registry of Acute Coronary Events (GRACE) score in Cox regression models, the association of high WMR with the cumulative incidence of MACE was preserved (overall patients (HR=1.85, 95% CI 1.1-3.12, p=0.02) and patients with a SYNTAX score <22 (HR=2.06, 95% CI 1.15-3.67, p=0.01). Conclusion The WMR was not related to CAD complexity, but it was associated with long-term clinical outcomes in patients with NSTEMI who underwent coronary angiography.

A Rare Autoinflammatory Disorder in a Pediatric Patient with Favorable Response to Etanercept: Sideroblastic Anemia with B Cell Immunodeficiency, Periodic Fevers, and Developmental Delay Syndrome.

Introduction: Sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome is caused by biallelic TRNT1 mutations. TRNT1 gene encodes a CCA-adding tRNA nucleotidyl transferase enzyme. Mutant TRNT1 results in immunodeficiency and anemia in various degrees, accompanied by several organ involvement. Case Presentation: We present here a 15-month old male, demonstrated brittle hair, growth hormone deficiency, recurrent fever, arthritis, recurrent infections, mild anemia, and hypogammaglobulinemia. The patient did not respond to colchicine treatment, and after establishing SIFD diagnosis with the presence of homozygote c.948-949delAAinsGG (p.Lys317Glu) mutation in TRNT1 gene, we commenced monthly intravenous immunoglobulin replacement and weekly subcutaneous etanercept. A rapid resolution of fever episodes and infections occurred after initiation of this treatment regimen. Afterward, both anemia and growth parameters have improved during follow-up. Conclusion: SIFD syndrome should be considered in patients with recurrent fever, arthritis, and growth retardation even in the absence of severe anemia and prominent hypogammaglobulinemia.

Xanthan-gelatin and xanthan-gelatin-keratin wound dressings for local delivery of Vitamin C.

Recently, functional dressings that can protect the wound area from dehydration and bacterial infection and support healing have gained importance in place of passive dressings. This study aimed to develop temporary and regenerative xanthan/gelatin (XGH) and keratin/xanthan/gelatin hydrogels (KXGHs) that have high absorption capacity and applicability as a wound dressing that can provide local delivery of Vitamin C (VC). Firstly, xanthan/gelatin hydrogels were produced by crosslinking with different glycerol concentrations and characterized to determine the hydrogel composition. According to their weight ratios, xanthan, gelatin, and glycerol hydrogels are named. If their weight ratio is 1:1:2 (w/w/w), the group name is selected as X1:GEL1:GLY2. X1:GEL1:GLY2 hydrogel was selected for biocompatibility, mechanical property, water vapor transmission rate (WVTR), and porosity. The addition of keratin to X1:GEL1:GLY2 improved L929 fibroblasts viability and increased protein release. Water vapor transmission of XGHs and KXGHs was between 3059.09 ± 126 and 4523 ± 133 g m-2 d-1; therefore, they can be suitable for granulating, low to moderate exudate wounds. XGH and KXGHs loaded with VC had higher water uptake, making it more convenient for exudate wounds. VC was released for 100 h, and VC containing XGHs and KXGHs increased the collagen synthesis of L929 fibroblasts. All of the hydrogels (XGH, KXGH, and VC-KXGHs) inhibited the bacteria transmission. In conclusion, our results suggest that VC-XGH and VC-KXGH can be candidates for temporary wound dressing materials for skin wounds.

Investigation of Genetic Causes in a Developmental Disorder: Oculoauriculovertebral Spectrum.

OBJECTIVE: Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated. DESIGN/SETTING/PATIENTS: A cohort of 23 Turkish patients with OAVS, referred to Hacettepe University Hospital, Department of Pediatric Genetics from 2008 to 2018, was included in this study. Minimal diagnostic criteria for OAVS were considered as unilateral microtia or hemifacial microsomia with preauricular skin tag. The cohort was clinically reevaluated for craniofacial and extracranial findings. Molecular etiology was investigated using candidate gene sequencing following copy number variant (CNV) analysis. WES was also performed for 2 of the selected patients. RESULTS: Patients in the study cohort presented similar demographic and phenotypic characteristics to previously described patients in the literature except for a higher frequency of bilaterality, cardiac findings, and intellectual disability/developmental delay. CNV analysis revealed a possible genetic etiology for 3 patients (13%). Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 (EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS. CONCLUSION: Detailed clinical evaluation for any patient with OAVS is recommended due to a high rate of accompanying systemic findings. We further expand the existing genetic heterogeneity of OAVS by identifying several CNVs and a phenotypically overlapping disorder, MFDM.

Two Siblings with Kaufman Oculocerebrofacial Syndrome Resembling Oculoauriculovertebral Spectrum.

Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder which represents a phenotype mainly involving craniofacial and neurodevelopmental manifestations due to UBE3B gene mutations. The vast majority of the affected individuals exhibit microcephaly, eye abnormalities, and typical facial gestalt including blepharophimosis, ptosis, telecanthus, upslanting palpebral fissures, dysplastic ears, and micrognathia. We encountered 2 siblings in whom severe psychomotor delay, distinctive facial features, hearing loss, and respiratory distress were observed. Some clinical manifestations of the patients, including epibulbar dermoid, microtia, and multiple preauricular tags, were reminiscent of the oculoauriculovertebral spectrum. However, 2 affected siblings exhibited a similar clinical picture consisting of microcephaly, severe developmental and cognitive disabilities, failure to thrive, and dysmorphic features, which were not fully consistent with oculoauriculovertebral spectrum. Also, hypoplastic nails, considered as a core manifestation of Coffin-Siris syndrome, were present in our patients. Therefore, whole-exome sequencing was carried out in order to identify the underlying genetic alterations, contributing to the complex phenotype shared by the 2 siblings. A homozygous pathogenic mutation was found in both affected siblings in the UBE3B gene which caused Kaufman oculocerebrofacial syndrome. Kaufman oculocerebrofacial syndrome should be considered among the autosomal recessive causes of blepharophimosis-mental retardation syndromes, particularly in populations with a high rate of consanguineous marriages, even if there are dysmorphic facial features that are not typically associated with the phenotype.

Three new cases of Crisponi /cold induced sweating syndrome (CS/CISS1) in Turkish families.

Crisponi syndrome/Cold Induced Sweating Syndrome 1 (CS/CISS1) is a rare, autosomal recessive, multisystemic disease. Hyperthermia attacks, abnormal contractions in the muscles of the face and oropharynx, respiratory distress, camptodactyly, and swallowing difficulty are the main features of the condition in the neonatal period. Patients experience cold-induced sweating attacks and progressive kyphoscoliosis in childhood and adolescence. Mutations in the cytokine receptor like factor 1 (CRLF1) gene causes the CISS1 (Cold- induced sweating syndrome type 1) disease (over 95% of patients). CRLF1 is located in the ciliary neurotrophic factor receptor (CNTFR) pathway, which plays an important role in development and maintenance of neurons in the nervous system. In this study three patients from Turkey, clinically and molecularly diagnosed with CS/CISS1, are presented. Hyperthermia, swallowing difficulty, camptodactyly and pursing of the lips were present in all patients, and foot deformity in one patient. In the first patient a homozygous nonsense mutation NM_004750.5: c.531G > A; p.(Trp177Ter) in the 4th exon was detected. In the second patient a homozygous nonsense mutation NM_004750.5: c.776C > A; p.(Ser259Ter) in the 5th exon was detected. The third patient was homozygous for a missense mutation NM_004750.5: c.935G > T; p.(Arg312Leu) in the 6th exon. Early diagnosis is very important in this syndrome since most patients die in the neonatal period. Therefore, physicians should be suspicious for this disease in patients with dysmorphic features, hyperthermia attacks, camptodactyly, pursing of lips while crying, and swallowing difficulty.

Genetic disorders with symptoms mimicking rheumatologic diseases: A single-center retrospective study.

Musculoskeletal symptoms may be due to noninflammatory causes, including genetic disorders. We aimed to examine the final genetic diagnosis in patients who presented with musculoskeletal complaints to the rheumatology department. Patients who presented to the Department of Pediatric Rheumatology and were referred to the pediatric genetic department between January 2015 and May 2019 were evaluated retrospectively. A total of 60 patients, 19 boys (31.66%), with a mean age of 12.46 ± 1.41 years were included in the study. The total consanguinity rate was 25%. The most common (29.5%) cause of referral to the pediatric genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one-third of the patients (n: 19) were diagnosed and followed up by the pediatric genetics department. The diagnoses of patients were as follows: camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome (n: 3); trichorhinophalangeal syndrome (n: 1); progressive pseudorheumatoid dysplasia (n: 2); LIG4 syndrome (n: 1); H syndrome (n: 1); spondyloenchondrodysplasia (SPENCD) (n: 3); and nonspecific connective tissue disorders (n: 8). In the differential diagnosis of patients who are referred to the Department of Pediatric Rheumatology with complaints of the musculoskeletal system, genetic disorders should also be considered.

Natural history of TRPV4-Related disorders: From skeletal dysplasia to neuromuscular phenotype.

TRPV4-related disorders constitute a broad spectrum of clinical phenotypes including several genetic skeletal and neuromuscular disorders, in which clinical variability and somewhat overlapping features are present. These disorders have previously been considered to be clinically distinct phenotypes before their molecular basis was discovered. However, with the identification of TRPV4 variants in the etiology, they are referred as TRPV4-related disorders (TRPV4-pathies), and are now mainly grouped into skeletal dysplasias and neuromuscular disorders. The skeletal dysplasia group includes metatropic dysplasia, parastremmatic dysplasia, spondyloepiphyseal dysplasia Maroteaux type, spondylometaphyseal dysplasia Kozlowski type, autosomal dominant brachyolmia, and familial digital arthropathy-brachydactyly, whereas the neuromuscular group includes congenital distal spinal muscular atrophy (SMA), scapuloperoneal SMA and Charcot-Marie-Tooth neuropathy type 2C with common manifestations of peripheral neuropathy, joint contractures, and respiratory system involvement. Apart from familial digital arthropathy-brachydactyly, skeletal dysplasia associated with TRPV4 pathogenic variants share some clinical features such as short stature with short trunk, spinal and pelvic changes with varying degrees of long bone involvement. Of note, there is considerable phenotypic overlap within and between both groups. Herein, we report on the clinical and molecular spectrum of 11 patients from six different families diagnosed with TRPV4-related disorders. This study yet represents the largest cohort of patients with TRPV4 variants from a single center in Turkey.