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![Clinical features of the patient in our study. (a-c) Axial and sagittal of the spine demonstrated an abnormal pathologic anchoring of the spinal cord to S1 in the caudal vertebral column and symptom of lipomyelomeningocele at the level of L4 and L5. The patient was also found to have spina bifida occulta from L4 to S1. Magnetic resonance imaging (MRI) showed a moderate scoliosis of her spine (a and c, MRI; b, anteroposterior X-ray). (d-f) The patient was also found to have normal craniofacial characteristics and long slender fingers and bilateral pes cavus. (g,h) A de novo missense mutation of c336C>G, p.C112W was found in patient (II-1) [Color figure can be viewed at wileyonlinelibrary.com]](profile/Kaiqiang-Sun-2/publication/331848838/figure/fig1/AS:890182140170240@1589247369391/Clinical-features-of-the-patient-in-our-study-a-c-Axial-and-sagittal-of-the-spine.png)
Clinical features of the patient in our study. (a-c) Axial and sagittal of the spine demonstrated an abnormal pathologic anchoring of the spinal cord to S1 in the caudal vertebral column and symptom of lipomyelomeningocele at the level of L4 and L5. The patient was also found to have spina bifida occulta from L4 to S1. Magnetic resonance imaging (MRI) showed a moderate scoliosis of her spine (a and c, MRI; b, anteroposterior X-ray). (d-f) The patient was also found to have normal craniofacial characteristics and long slender fingers and bilateral pes cavus. (g,h) A de novo missense mutation of c336C>G, p.C112W was found in patient (II-1) [Color figure can be viewed at wileyonlinelibrary.com]
Source publication
Shprintzen‐Goldberg syndrome (SGS) is a rare systemic connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular manifestations. It is associated with a significant risk of intellectual disability, a feature which distinguishes it from Marfan and Loeys‐Dietz syndromes. SGS is mainly caused by mutations in the SKI gene, a...
Contexts in source publication
Context 1
... was verified by target PCR and Sanger sequencing and confirmed to be a de novo mutation (Figure 1h). Adding our finding to previously described SKI mutations, a mutation hotspot was apparently revealed in the DHD domain of exon 1. ...
Context 2
... 10-year-old female patient reported here was initially diagnosed with lipomeningomyelocele, tethered cord, spina bifida, and mild thoracolumbar scoliosis (Figure 1a-c). She had no SGS-related clinical findings apart from long fingers. ...
Context 3
... is tall and slim with her height at the 97th centile for age and her weight just above the 25th centile so she has somewhat marfanoid habitus. She has pes cavus, normal intellectual development and no craniofacial (Figure 1d-f) or cardiovascular abnormalities (Supporting Information Figure S1A-D). ES revealed a de novo missense mutation in SKI exon 1 DHD domain, the gene associated with SGS (Figure 1h). ...
Context 4
... is tall and slim with her height at the 97th centile for age and her weight just above the 25th centile so she has somewhat marfanoid habitus. She has pes cavus, normal intellectual development and no craniofacial (Figure 1d-f) or cardiovascular abnormalities (Supporting Information Figure S1A-D). ES revealed a de novo missense mutation in SKI exon 1 DHD domain, the gene associated with SGS (Figure 1h). ...
Context 5
... has pes cavus, normal intellectual development and no craniofacial (Figure 1d-f) or cardiovascular abnormalities (Supporting Information Figure S1A-D). ES revealed a de novo missense mutation in SKI exon 1 DHD domain, the gene associated with SGS (Figure 1h). One other patient with spina bifida occulta from The SKI proto-oncogene is a negative regulator of the TGF-β signaling pathway, which participates widely in cellular biological activities such as cell proliferation, differentiation, apoptosis, and migration (Massague, 2012;Weiss & Attisano, 2013). ...
Similar publications
SKI pathogenic variations are associated with Shprintzen–Goldberg Syndrome (SGS), a rare systemic connective tissue disorder characterized by craniofacial, skeletal and cardiovascular features. So far, the clinical description, including intellectual disability, has been relatively homogeneous, and the known pathogenic variations were located in tw...
Citations
... (d) [4,8]. (e) [8,9,10]. (Supplementary Materials) ...
Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a rare autosomal dominant condition that was first documented in literature in 1982. The disorder is caused by pathogenic variants in the proto-oncogene SKI gene, a known suppressor of TGF-β activity, located on chromosome 1p36. There is considerable phenotypic overlap with Marfan and Loeys-Dietz syndromes. Common clinical features of SGS include craniosynostosis, marfanoid habitus, hypotonia, dysmorphic facies, cardiovascular anomalies, and other skeletal and connective tissue abnormalities. Ocular manifestations may include hypertelorism, downslanting palpebral fissures, proptosis, myopia, and ectopia lentis. We describe a 25-year-old male with the syndrome. Genetic analysis revealed a novel c.350G>A (p.Arg117His) de novo variant, which was predicted to be pathogenic by the CTGT laboratory. The patient presented with dysmorphic features, marfanoid habitus, severe joint contractures, mitral valve insufficiency, aortic root dilatation, and a history of seizures. His ocular manifestations included hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia. Ophthalmic manifestations are an integral component of the syndrome; however, they have not been well characterized in the literature. From a systematic review of previously published cases to date, we summarize the eye and ocular adnexa manifestations reported.
... 1 3 inframe deletions that cluster in two distinct N-terminally located regions of the protein (Doyle et al. 2012;Carmignac et al. 2012;Au et al. 2014;Schepers et al. 2015;Poninska et al. 2016;Saito et al. 2017;Zhang et al. 2019). The first region, known as the R-SMAD binding domain, is located in the SMAD2/3-binding domain of SKI (residues 20-35). ...
... Her clinical presentation, which included lipomeningomyelocele, tethered cord, and spina bifida, was not totally consistent with SGS. Apart from a marfanoid habitus and long slender fingers, she did not have the typical SGS-related clinical findings such as intellectual disability, or craniofacial and cardiovascular abnormalities (Zhang et al. 2019). ...
... e Patient 9: note hypertelorism, down-slanting eyes, proptosis, arachnodactyly and joint contractures et al. 2017). In the 43 patients carrying a pathogenic variant in the SKI gene described in the literature, the craniofacial phenotype was extremely consistent, except for one patient reported by Zhang (Zhang et al. 2019). More specifically, features including dolichocephaly, hypertelorism, down-slanting eyes, malar hypoplasia, and high/narrow 1 3 palate were found in more than 90% of probands (Schepers et al. 2015). ...
SKI pathogenic variations are associated with Shprintzen–Goldberg Syndrome (SGS), a rare systemic connective tissue disorder characterized by craniofacial, skeletal and cardiovascular features. So far, the clinical description, including intellectual disability, has been relatively homogeneous, and the known pathogenic variations were located in two different hotspots of the SKI gene. In the course of diagnosing Marfan syndrome and related disorders, we identified nine sporadic probands (aged 2–47 years) carrying three different likely pathogenic or pathogenic variants in the SKI gene affecting the same amino acid (Thr180). Seven of these molecular events were confirmed de novo. All probands displayed a milder morphological phenotype with a marfanoid habitus that did not initially lead to a clinical diagnosis of SGS. Only three of them had learning disorders, and none had intellectual disability. Six out of nine presented thoracic aortic aneurysm, which led to preventive surgery in the oldest case. This report extends the phenotypic spectrum of variants identified in the SKI gene. We describe a new mutational hotspot associated with a marfanoid syndrome with no intellectual disability. Cardiovascular involvement was confirmed in a significant number of cases, highlighting the importance of accurately diagnosing SGS and ensuring appropriate medical treatment and follow-up.
Kraniyosinostoz, kraniyal sütürlerin erken kapanması olarak tanımlanmaktadır. Çocuklarda yaklaşık prevalansının 1/1400 ile 1/2100 seviyesinde olduğu tahmin edilmektedir. Kraniyosinostozların oluşumundan rahim içi ortam, poligenik arka plan, beyin büyüme ve gelişimi, spesifik monogenik ve kromozomal bozukluklar gibi bir çok heterojen faktörün etkileşimi sorumlu tutulmaktadır. Bu sebeple etiyolojik değerlendirme detaylı ve basamaklı incelemeyi gerektirmektedir. Klinik seyir içerisinde ortaya çıkabilecek komplikasyonlar ve eşlik edebilecek diğer sistemlerle ilgili problemler sebebiyle yönetimi çoklu disiplinli bir ekip ile gerçekleştirilmelidir. Kraniyosinostozlar literatürdeki birçok derleme ve çalışmada, patofizyoloji, tanısal yaklaşımlar, genetik temel, moleküler tanı algoritmaları ve hastalığın yönetimi gibi farklı yönleri ile değerlendirilmiştir. Bu derlemede ise kraniyosinostozlar ilişkili dismorfoloji terimleri, dismorfik değerlendirmede önemli özellikler, sendromik/nonsendromik kraniyosinostozların ayrımı, tanınabilir sendromik kraniyosinostozların bir özeti ve moleküler tanı yaklaşımları konuları açısından ele alınacaktır.
Patient: Female, 9
Final Diagnosis: Mandibular hypoplasia secondary to Shprintzen-Goldberg Syndrome
Symptoms: Difficulty swallowing
Medication: —
Clinical Procedure: Bilateral mandibular osteotomy and distraction for mandibular hypolasia
Specialty: Neurosurgery
Objective
Rare disease
Background
Shprintzen-Goldberg syndrome (SGS) is an extremely rare collagenopathy, most often caused by autosomal-dominant mutations in the SKI proto-oncogene, which is a component of the transforming growth factor beta (TGF-β) signaling pathway. Approximately 50–60 cases of SGS have been recorded in the literature worldwide since its discovery in 1982. This collagen disorder affects bone and vascular development throughout the body, resulting in craniosynostosis, scoliosis, chest deformities, and aortic root dilation. Patients may have problems in the central nervous system, including Chiari 1 malformation, hydrocephalus, and dilation of the lateral ventricles. Unfortunately, the symptoms of SGS closely parallel those of related collagenopathies involving mutations in the TGF-β signaling pathway, which makes accurate diagnosis difficult without genetic testing, especially in cases with complex presentation.
Case Report
In this report we present the unique and complex disease manifestations in a 9-year-old girl with SGS. The patient had severe cervical spinal instability that resolved after surgical occipital-C4 fusion with an autograft from the rib. Midface distraction surgery was used to treat the patient’s craniosynostosis and related facial deformities. This surgery was complicated by loss of 750 mL of blood due to insufficient dura and prominent vasculature.
Conclusions
Connective tissue symptoms associated with SGS can involve dural and vascular problems, as seen in this case report. Thus, the risk of extreme blood loss should be anticipated any time midface distraction surgery is performed on an SGS patient. Continued research is needed to define how this case relates to the SGS patient population.
