Further Delineation of the Proximal 16p11.2 Microdeletion Syndrome: Novel Findings Among 22 New Individuals.

The recurrent chromosome 16p11.2 BP4-BP5 microdeletion (MIM #611913) predisposes to a neurodevelopmental disorder with variable associated congenital anomalies and susceptibility to early-onset obesity. We identified 22 new individuals with proximal 16p11.2 deletions through retrospective data analysis at our institution and performed phenotyping through in-depth chart review. Our cohort exhibited a spectrum of neurodevelopmental abnormalities largely consistent with other publications, however they also were found to have a higher rate than expected of congenital anomalies, some of which have not yet been reported in association with 16p11.2 microdeletions to our knowledge. This series contributes to the body of data on this population, which we anticipate will continue to evolve along with increased uptake of genetic testing.

Presentation of ichthyosis after substrate reduction therapy in Gaucher type 1.

We describe a case in which a type 1 Gaucher patient developed ichthyosis weeks after starting substrate reduction therapy (SRT) with eliglustat. There are no reports of ichthyosis in the literature in enzyme replacement or SRT for Gaucher disease. Ichthyosis is seen with type 2 and 3 Gaucher disease, but not type 1. This raises the question: Why would a patient develop ichthyosis after starting SRT?

Complete Blood Count Values Over Time in Young Children During the Dengue Virus Epidemic in the Dominican Republic From 2018 to 2020.

Background: Dengue fever (DF) is a mosquito-borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low-resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1-10 of fever. Participants were classified as DF-negative and DF-positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed-models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF-positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk-stratified screenings for resource-limited settings.

Expanding the phenotype of neurofibromatosis type 1 microdeletion syndrome.

Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics. This cohort consists of 57 individuals with NF-1 microdeletion syndrome (28 type-1, 4 type-2, 2 type-3, 9 atypical deletions, and 14 indeterminate). We note 38/56 (67.9%) with describable facial features, 25/57 (43.8%) with plexiform neurofibromas, and 3/57 (5.2%) with malignant peripheral nerve sheath tumors within the observed period. The most reported neurodevelopmental manifestations from school-age or older individuals included 39/49 (79.6%) with developmental delays, 35/49 (71.4%) with expressive and/or receptive speech delays, 33/41 (80.5%) with learning difficulties, and 23/42 (54.8%) with attention-deficit/hyperactivity disorder. Full-scale IQ testing data was available for 22 individuals (range: 50-96). Of the 21 adults in this cohort, 14/21 (66.7%) graduated from high school, and 4/21 (19.0%) had some college experience. Many individuals received academic support (i.e., special education, individual education plan). In this cohort, neurocognitive outcomes in adults varied more than typically reported in the literature.

Clinical Outcomes and Management Strategies for Capitellum and Trochlea Fractures: A Systematic Review.

Purpose: Capitellum and trochlea fractures, also referred to as coronal shear fractures of the distal humerus, are infrequent yet challenging intra-articular fractures of the elbow. There are a variety of surgical approaches and fixation methods with often variable outcomes. This systematic review investigates interventions, outcomes and complications of capitellum and trochlea fractures. Methods: A systematic review of studies published in MEDLINE, EMBASE, Web of Science and Cumulative Index to Nursing and Allied Health literature (CINAHL) was conducted to assess the clinical outcomes of capitellum and trochlea fractures managed surgically. Data on patient demographics, surgical approach, implant usage, postoperative outcomes and complications were compiled. Results: Forty-one studies met the inclusion criteria with a total of 700 patients. Surgical interventions primarily utilized either the lateral (79%) or antero-lateral (15%) approaches with headless compression screws as the most common fixation method (68%). Clinical outcomes were measured using the Mayo Elbow Performance Index (MEPI) with a mean score of 89.9 (±2.6) and the DASH score with a mean of 16.9 (±7.3). Elbow range of motion showed a mean flexion of 126.3° (±19.4), extension of 5.71° (±11.8), pronation of 75.23° (±12.2), and supination of 76.6° (±9.8). The mean flexion-extension arc was 113.7° (±16.9), and the mean pronation-supination arc was 165.31° (±9.41). Complications occurred in 19.8% of cases, with re-interventions required in 8.3% of cases, mainly due to symptomatic implants and elbow stiffness requiring surgical release. Other complications included implant removal (10.4%), overall reported stiff elbows (6%), nerve palsies (2%), non-union (1.5%), and infection (1.2%). Conclusion: The treatment of capitellum and trochlea fractures yields satisfactory outcomes but has a considerable rate of complications and reoperations primarily due to symptomatic implants and elbow stiffness. There is noteworthy variability in the achieved range of motion, suggesting unpredictable outcomes. Deficits in functionality and range of motion are common after surgery, especially with more complex injury patterns.

Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome reveal deficits of circadian rhythm and sleep-wake behavior.

Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature. Here, we report a cohort of 28 individuals with SKS that represent nine MTOR pathogenic variants. We conducted a detailed natural history study and found pathophysiological deficits among individuals with SKS in addition to the common neurodevelopmental symptoms. These symptoms include sleep-wake disturbance, hyperphagia, and hyperactivity, indicative of homeostatic imbalance. To characterize these variants, we developed cell models and characterized their functional consequences. We showed that these SKS variants display a range of mechanistic target of rapamycin (mTOR) activities and respond to the mTOR inhibitor, rapamycin, differently. For example, the R1480_C1483del variant we identified here and the previously known C1483F are more active than wild-type controls and less responsive to rapamycin. Further, we showed that SKS mutations dampened circadian rhythms and low-dose rapamycin improved the rhythm amplitude, suggesting that optimal mTOR activity is required for normal circadian function. As SKS is caused by gain-of-function mutations in MTOR, rapamycin was used to treat several patients. While higher doses of rapamycin caused delayed sleep-wake phase disorder in a subset of patients, optimized lower doses improved sleep. Our study expands the clinical and molecular spectrum of SKS and supports further studies for mechanism-guided treatment options to improve sleep-wake behavior and overall health.

Aminotransferase trends in propionic acidemia.

Propionic acidemia is a metabolic condition with multiple serious acute and chronic presentations that require strict monitoring. Literature on liver function abnormalities in propionic acidemia is scarce, and the mechanism of liver impairment in this condition remains unclear. Currently, there is no indication for liver-function tests during follow-up and their clinical or prognostic utility is unknown. This study aimed to determine aminotransferase trends in individuals with propionic acidemia at a single institution. We retrospectively evaluated and classified the aminotransferases of 12 patients with propionic acidemia during hospital admissions and routine office visits. The present findings suggest that aminotransferase elevations are very common in this population and can persist beyond acute illness. During hospitalization events, aminotransferases were not a predictor of severity, duration of stay, and readmission within 1 month. Understanding aminotransferase trends in these patients will help clinicians make decisions in the acute setting and potentially in the follow-up of new therapies.

Dandy-Walker malformation in an individual with ABL1 variant.

Dandy-Walker malformation (DWM) is often sporadic, but there are a growing number of genetic disorders that have been associated with this condition. We present a female individual with a de novo variant in ABL1, c.734A>G (p.Y245), who was diagnosed prenatally with DWM. ABL1-related neurodevelopmental disorder was recently identified but brain malformations have not been well characterized to date. We reviewed the published literature and identified one additional individual with DWM and ABL1-related disorder, which suggests a possible association with this malformation.

Operative Management of Extensor Carpi Ulnaris Instability: A Systematic Review.

Background Posttraumatic extensor carpi ulnaris (ECU) instability is an increasingly recognized cause of ulnar-sided wrist pain that occurs when the ECU subsheath is disrupted. Purpose The purpose of this systematic review was to assess outcomes of operatively treated posttraumatic ECU instability. Methods A systematic search of Medline, Embase, Web of Science, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases was performed using "extensor carpi ulnaris" as the keyword. Studies were systematically screened and data extracted independently by two reviewers. Results Eight retrospective studies met the inclusion criteria with a total of 97 wrists. The mean age was 32 years (13-61). Patients underwent either primary repair (40%) using sutures and anchors, or reconstruction (60%) using extensor retinaculum flaps. One study performed deepening of the osseous ulnar groove. Two studies compared preoperative and postoperative values. They both reported a significant improvement in pain scores, functional scoring instruments, satisfaction, and grip strength. The rest of the studies reported similarly favorable outcomes across the same outcomes. Concomitant pathologies were identified in 66% of the study population. Complications occurred in 9% of the sample size, including ECU tendinitis, ulnar sensory nerve irritation, and reintervention for concomitant pathology. None of the studies reported recurrence or reruptures. However, five patients (6.7%) did not return to their previous activity level. Conclusion Patients can expect favorable outcomes with a potentially low complication rate. Nevertheless, the heterogeneity of the sample population, operative techniques, and outcome measures warrant further standardized studies. Level of Evidence IV.

Interlocking intramedullary nail for forearm diaphyseal fractures in adults-A systematic review and meta-analysis of outcomes and complications.

PURPOSE: The purpose of this systematic review is to examine the outcomes, complications, and potential advantages of using anatomical interlocking intramedullary nails (IMN) in the treatment of radius and ulnar shaft diaphyseal fractures in adults. METHODS: Medline, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched between January 2000 and January 2023. Studies meeting criteria were observational or randomized controlled trials evaluating outcomes in IMN for adult diaphyseal forearm fractures. Standardized data extraction was performed and a quality assessment tool was used to evaluate individual study methodology. Descriptive statistics for interventions, functional outcomes, and complications were reported. Meta-analysis was performed for patient-reported outcome measures and operative time. RESULTS: A total of 29 studies involving 1268 patients were included with 764 (60%) undergoing IMN, 21% open reduction and internal fixation (ORIF), and 9% hybrid fixation. There was no significant difference between groups in DASH and Grace-Eversmann scores. Operative time was significantly shorter in IMN compared with ORIF. The DASH scores were: 13.1 ± 6.04 for IMN, 10.17 ± 3.98 for ORIF, and 15.5 ± 0.63 in hybrids. Mean operative time was 65.3 ± 28.7 in ORIF and 50.8 ± 17.7 in IMN. Complication rates were 16.7% in the IMN group, 14.9% in ORIF, and 6.3% in hybrid constructs. There were 11 cases of extensor pollicis rupture in the IMN group. Average IMN pronation and supination were 78.3° ± 7.9° and 73° ± 5.0°, respectively. Average ORIF pronation and supination was 82.15° ± 1.9° and 79.7° ± 4.5°, respectively. CONCLUSIONS: Similar functional outcomes and complication rates along with shorter operative times can be achieved with IMN compared with ORIF. The use of IMN is promising, however, higher quality evidence is required to assess appropriate indications, subtle differences in range of motion, implant-related complications, and cost-effectiveness. Trail Registration PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42022362353).

Homozygosity for disease-causing variants in AMT and GLDC in a patient with severe nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is a relatively well-characterized inborn error of metabolism that results in a combination of lethargy, hypotonia, seizures, developmental arrest, and, in severe cases, death early in life. Three genes encoding components of the glycine cleavage enzyme system-GLDC, AMT, and GCSH-are independently associated with NKH. We report on a patient with severe NKH in whom the homozygous pathogenic variant in AMT (NM_000481.3):c.602_603del (p.Lys201Thrfs*75) and the homozygous likely pathogenic variant in GLDC(NM_000170.2):c.2852C>A (p.Ser951Tyr) were both identified. Our patient demonstrates a novel combination of two homozygous disease-causing variants impacting the glycine cleavage pathway at two different components, and elicits management- and genetic counseling-related challenges for the family.

Integrating cryptic diversity into coral evolution, symbiosis and conservation.

Understanding how diversity evolves and is maintained is critical to predicting the future trajectories of ecosystems under climate change; however, our understanding of these processes is limited in marine systems. Corals, which engineer reef ecosystems, are critically threatened by climate change, and global efforts are underway to conserve and restore populations as attempts to mitigate ocean warming continue. Recently, sequencing efforts have uncovered widespread undescribed coral diversity, including 'cryptic lineages'-genetically distinct but morphologically similar coral taxa. Such cryptic lineages have been identified in at least 24 coral genera spanning the anthozoan phylogeny and across ocean basins. These cryptic lineages co-occur in many reef systems, but their distributions often differ among habitats. Research suggests that cryptic lineages are ecologically specialized and several examples demonstrate differences in thermal tolerance, highlighting the critical implications of this diversity for predicting coral responses to future warming. Here, we draw attention to recent discoveries, discuss how cryptic diversity affects the study of coral adaptation and acclimation to future environments, explore how it shapes symbiotic partnerships, and highlight challenges and opportunities for conservation and restoration efforts.

Role of CAMK2D in neurodevelopment and associated conditions.

The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes-CAMK2A, CAMK2B, CAMK2G, and CAMK2D-of which the first three have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in humans. We identified eight individuals harboring heterozygous variants in CAMK2D who display symptoms of intellectual disability, delayed speech, behavioral problems, and dilated cardiomyopathy. The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms. Together, we describe a cohort of individuals with neurodevelopmental disorders and cardiac anomalies, harboring pathogenic variants in CAMK2D, confirming an important role for the CAMK2D isozyme in both heart and brain function.

A Study on the Efficacy and Safety of Pipeline Shield Stents and Nonmodified Surface Flow-Diverting Stents in Patients with Intracranial Aneurysms.

BACKGROUND: Few studies have compared the Pipeline Shield stents with previous generations of flow-diverting stents (FDSs) for the treatment of unruptured intracranial aneurysms. This study aimed to evaluate the efficacy and safety of Pipeline Shield stents and FDSs without modified surfaces. METHODS: The present evaluation is a retrospective cohort study of patients endovascularly treated with Pipeline Shield stents or FDSs without modified surfaces for unruptured intracranial aneurysms between January 2014 and June 2022. The data analyzed were obtained from the anonymized database of our institution's interventional radiology service. RESULTS: A total of 147 patients with 155 unruptured intracranial aneurysms were included. Of the 155 aneurysms, 96 were treated with Pipeline Shield stents and 59 with FDSs without modified surfaces. The aneurysms treated with Pipeline Shield stents had higher 6-month (O'Kelly-Marotta [OKM] D; 87.5% vs. 71.4%; P = 0.025) and 1-year (OKM D; 82.5% vs. 63.0%; P = 0.047) occlusion rates than the aneurysms treated using FDSs without modified surfaces. No differences between the devices were found at the 1-year follow-up in the incidence of ischemic stroke (P = 0.939) or hemorrhagic complications (P = 0.559). CONCLUSIONS: Pipeline Shield stents demonstrated superior complete occlusion rates (OKM D) at both the 6-month and the 1-year follow-up assessments compared with nonmodified surface FDSs. No significant differences were found in the safety profiles between the 2 types of stents with regard to thromboembolic complications and ischemic events. Further research with larger study populations is necessary to validate these findings.

Proximal Row Carpectomy With Soft Tissue Interposition: A Systematic Review of Clinical Outcomes.

Proximal row carpectomy (PRC) with soft tissue interposition arthroplasty (STIA) presents an alternative approach to addressing wrist arthritis patterns involving the capitate and/or lunate fossa, in lieu of wrist arthrodesis. This systematic review aimed to evaluate clinical outcomes and techniques associated with PRC-STIA in patients with advanced wrist arthritis. We conducted a systematic review using databases including PubMed, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials. Inclusion criteria involved articles reporting outcomes of patients who underwent PRC-STIA with at least 1 relevant outcome. The analysis encompassed 8 studies involving 106 patients (108 wrists) meeting the inclusion criteria. A majority of patients were men (69%, n = 88), with a mean age of 54.4 ± 12.7 years and an average follow-up of 4.8 ± 6.3 years. Dorsal capsule was the most commonly interposed tissue (63%, 5 out of 8 studies). Patients receiving STIA achieved comparable patient-reported outcome measures scores to those undergoing PRC alone. Postoperative pain, measured by the Visual Analog Scale, averaged 3.7 ± 0.6. The Disabilities of the Arm, Shoulder, and Hand score averaged 27.8 ± 8, while the Patient-Rated Wrist Evaluation score averaged 41.5 ± 25.9. Five complications were reported in three studies. The addition of STIA into PRC for patients with capitate and/or lunate fossa cartilage degeneration yielded outcomes akin to traditional PRC, improving wrist function, pain, and grip strength in a safe and straightforward manner. Future research should prioritize high-quality comparative studies, extended follow-up periods, and standardized core outcome measures for a more comprehensive understanding of its role in wrist arthritis treatment.

Outcomes and Associated Extracardiac Malformations in Neonates from Colombia with Severe Congenital Heart Disease.

Congenital heart disease (CHD) is a common structural anomaly, affecting ~ 1% of live births worldwide. Advancements in medical and surgical management have significantly improved survival for children with CHD, however, extracardiac malformations (ECM) continue to be a significant cause of morbidity and mortality. Despite clinical significance, there is limited literature available on ECM in neonates with CHD, especially from Latin America. A cross-sectional study of neonates with severe CHD evaluated by the medical-surgical board team at Fundación Cardiovascular de Colombia from 2014 to 2019 was completed to characterize morbidity, mortality, surgical outcomes, and ECM. Demographics and surgical outcomes were compared between neonates with and without ECM. Medical record data were abstracted and descriptive statistical analysis was performed. Of 378 neonates with CHD, 262 had isolated CHD (69.3%) and 116 had ECM (30.7%). The most common ECM was gastrointestinal (n = 18, 15.5%) followed by central nervous system (n = 14, 12%). Most neonates required a biventricular surgical approach (n = 220, 58.2%). Genetic testing was performed more often for neonates with ECM (n = 65, 56%) than neonates with isolated CHD (n = 14, 5.3%). Neonates with ECM had lower birth weight, longer hospital stays, and higher postsurgical complications rates. There was no difference in survival between groups. Overall, Screening for ECM in neonates with CHD is important and identification of ECM can guide clinical decision-making. These findings have important implications for pediatric healthcare providers, especially in low- and middle-income countries, where the burden of CHD is high and resources for managing CHD and extracardiac malformations may be limited.

Prenatal and infantile diagnosis of craniosynostosis in individuals with RASopathies.

Fetuses with RASopathies can have a wide variety of anomalies including increased nuchal translucency, hydrops fetalis, and structural anomalies (typically cardiac and renal). There are few reports that describe prenatal-onset craniosynostosis in association with a RASopathy diagnosis. We present clinical and molecular characteristics of five individuals with RASopathy and craniosynostosis. Two were diagnosed with craniosynostosis prenatally, 1 was diagnosed as a neonate, and 2 had evidence of craniosynostosis noted as neonates without formal diagnosis until later. Two of these individuals have Noonan syndrome (PTPN11 and KRAS variants) and three individuals have Cardiofaciocutaneous syndrome (KRAS variants). Three individuals had single suture synostosis and two had multiple suture involvement. The most common sutures involved were sagittal (n = 3), followed by coronal (n = 3), and lambdoid (n = 2) sutures. This case series confirms craniosynostosis as one of the prenatal findings in individuals with RASopathies and emphasizes the importance of considering a RASopathy diagnosis in fetuses with multiple anomalies in combination with craniosynostosis.

The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy.

Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in-person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician-scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self-advocates and early-stage investigators were featured throughout the program to encourage a sustainable, diverse, long-term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies.

Treatment-naive and post-treatment glucosylsphingosine (lyso-GL1) levels in a cohort of pediatric patients with Gaucher disease.

Glucosylsphingosine (lyso-GL1) is a biomarker used to monitor disease and treatment response in Gaucher disease. Data from adults show that higher values of lyso-GL1 are associated with increased disease progression, however similar data in the pediatric population is lacking. In a cohort of pediatric patients, we present a relationship between lyso-GL1 value and Gaucher type, age, and treatment response. Data from this study may serve as a reference for providers monitoring children with Gaucher disease.

Clinical and ocular abnormalities in DEGCAGS syndrome-Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities.

PURPOSE: To describe clinical and ocular abnormalities in a case of Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). METHODS: A clinical report. CASE DESCRIPTION: An infant born to a consanguineous Middle Eastern family who was delivered by cesarean section because of in utero growth restriction, premature labor, and breech presentation. Post-partum medical problems included hypotension, generalized hypotonia, bradycardia, apnea requiring resuscitation and positive pressure ventilation, facial dysmorphia, skeletal malformations, and disorders of the gastrointestinal, immune, urinary, respiratory, cardiac, and visual systems. The family reported that a previous child had severe hypotonia at birth and was given the diagnosis of hypoxic ischemic encephalopathy; that child remains on a ventilator in a chronic care facility. Our patient was found to be homozygous for a novel pathogenic missense variant in theZNF699 zinc finger gene on chromosome 19p13 causing a syndrome known as Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). We review this variable syndrome, including abnormalities of the visual system not described previously. CONCLUSIONS: We describe the 15th child to be presumably identified with the DEGCAGS syndrome and the first individual with homozygous missense variants in the ZNF699 gene who had complete clinical examination and detailed retinal imaging.