Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Eye Manifestations of Shprintzen-Goldberg Craniosynostosis Syndrome: A Case Report and Systematic Review.

ABSTRACT: 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.

SUBMITTER: Choi JH

PROVIDER: S-EPMC7895601 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A Rare Case of Shprintzen-Goldberg craniosynostosis syndrome with Hirschsprung disorder: Dental characteristics and its Clinical Management.

Project description:Shprintzen-Goldberg syndrome (SGS) is an autosomal dominant syndrome caused by de novo gene mutations. It is characterized by a number of congenital defects such as craniofacial, skeletal, neurological, and connective tissue abnormalities. It is characterized by craniosynostosis and marfanoid features. To our knowledge, approximately 75 shprintzen-goldberg syndrome cases have been documented since it was first described in 1982. Rare cases of shprintzen-goldberg syndrome have been reported in which the mutated gene was inherited from an unaffected parent through their germline cells i.e., egg or sperm cells. This is a case report of a 6-year-old boy with clinically diagnosed Shprintzen-Goldberg Syndrome with Hirschsprung disease. Patient reported with multiple caries and malpositioned teeth. The treatment initiated with awareness about cariogenic foods, oral hygiene instructions and diet counselling. Subsequently, comprehensive rehabilitation was done. Key words:Dental management, Craniosynostosis, Hirschsprung disorder.

| S-EPMC10767731 | biostudies-literature

Complications of Insufficient Dura and Blood Loss During Surgical Intervention in Shprintzen-Goldberg Syndrome: A Case Report.

Project description: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-ß) 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-ß 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.

| S-EPMC6698069 | biostudies-literature

Shprintzen-Goldberg syndrome presenting as umbilical hernia in an Indian child.

Project description:Shprintzen-Goldberg syndrome (S-G) is a rare connective tissue disorder characterised by craniosynostosis, craniofacial dysmorphism, skeletal, cardiovascular, neurological, and other abnormalities. We herein present a case of a five-year-old Indian child who presented to our clinic with reducible umbilical hernia since birth, mental retardation, and delayed developmental milestones. After meticulous clinical examination with subsequent integration of clinical findings and investigations, we diagnosed her to possibly have Shprintzen-Goldberg syndrome. An attempt to compare the findings of our index case with the classical features as described by Greally et al. has been made. Given the rarity of this syndrome and the paucity of medical literature measuring the magnitude of this condition in the Indian population, this case serves to promote awareness of this rare entity.

| S-EPMC3941576 | biostudies-literature

Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome.

Project description:Goldberg-Shprintzen syndrome (OMIM 609460) (GOSHS) is an autosomal recessive multiple congenital anomaly syndrome distinguished by intellectual disability, microcephaly, and dysmorphic facial characteristics. Most affected individuals also have Hirschsprung disease and/or gyral abnormalities of the brain. This syndrome has been associated with KIAA1279 gene mutations at 10q22.1. Here we report a 16 yr old male patient referred to Center for Comprehensive Genetic Services, Tehran, Iran in 2015 with cardinal features of GOSHS in addition to refractory seizures. Whole exome sequencing in the patient revealed a novel nonsense (stop gain) homozygous mutation in KIAA1279 gene (KIAA1279: NM_015634:exon6:c.C976T:p.Q326X). Considering the wide range of phenotypic variations in GOSHS, relying on phenotypic characteristics for discrimination of GOSH from similar syndromes may lead to misdiagnosis. Consequently, molecular diagnostic tools would help in accurate diagnosis of such overlapping phenotypes.

| S-EPMC5329763 | biostudies-literature

Mutations in the TGF-? repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.

Project description:Elevated transforming growth factor (TGF)-? signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-? signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-? in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-? activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-? signaling cascades and higher expression of TGF-?-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-? signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm.

| S-EPMC3545695 | biostudies-literature

In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome.

Project description:Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mutation was found in a cohort of 11 individuals with other marfanoid-craniosynostosis phenotypes. The interaction between SKI and Smad2/3 and Smad 4 regulates TGF-? signaling, and the pattern of anomalies in Ski-deficient mice corresponds to the clinical manifestations of SGS. These findings define SGS as a member of the family of diseases associated with the TGF-?-signaling pathway.

| S-EPMC3487125 | biostudies-literature

A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome).

Project description:Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family. A fourth child showed similar clinical features, with the exception of Hirschsprung disease. The association of these abnormalities in these children represents the Goldberg-Shprintzen syndrome (OMIM 235730). Mutation scanning of genes potentially involved in Hirschsprung disease, RET, GDNF, EDN3, and EDNRB, showed a sequence variant, Ser305Asn, in exon 4 of the EDNRB gene in the index patient of this family. The Ser305Asn substitution present in two of the four patients and four healthy relatives and absent in one of the remaining two patients illustrates the difficulties in interpreting the presence of mutations in families with Hirschsprung disease. It is unlikely that the EDNRB variant contributes to the phenotype. This consanguineous family might be useful for the identification of a Goldberg-Shprintzen locus.

| S-EPMC1734390 | biostudies-literature

Multiple Functions of KBP in Neural Development Underlie Brain Anomalies in Goldberg-Shprintzen Syndrome.

Project description:Kinesin-binding protein (KBP; KIF1BP; KIAA1279) functions as a regulator for a subset of kinesins, many of which play important roles in neural development. Previous studies have shown that KBP is expressed in nearly all tissue with cytoplasmic localization. Autosomal recessive mutations in KIAA1279 cause a rare neurological disorder, Goldberg-Shprintzen syndrome (GOSHS), characterized by microcephaly, polymicrogyria, intellectual disability, axonal neuropathy, thin corpus callosum and peripheral neuropathy. Most KIAA1279 mutations found in GOSHS patients are homozygous nonsense mutations that result in KBP loss-of-function. However, it is not fully understood how KBP dysfunction causes these defects. Here, we used in utero electroporation (IUE) to express KBP short hairpin RNA (shRNA) with green fluorescent protein (GFP) in neural progenitor cells of embryonic day (E) 14 mice, and collected brain slices at different developmental stages. By immunostaining of neuronal lineage markers, we found that KBP knockdown does not affect the neural differentiation process. However, at 4 days post IUE, many cells were located in the intermediate zone (IZ). Moreover, at postnatal day (P) 6, about one third of the cells, which have become mature neurons, remained ectopically in the white matter (WM), while cells that have reached Layer II/III of the cortex showed impaired dendritic outgrowth and axonal projection. We also found that KBP knockdown induces apoptosis during the postnatal period. Our findings indicate that loss of KBP function leads to defects in neuronal migration, morphogenesis, maturation, and survival, which may be responsible for brain phenotypes observed in GOSHS.

| S-EPMC6838004 | biostudies-literature

KBP interacts with SCG10, linking Goldberg-Shprintzen syndrome to microtubule dynamics and neuronal differentiation.

Project description:Goldberg-Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo. To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.

| S-EPMC7297230 | biostudies-literature

Goldberg-Shprintzen Syndrome Associated with a Novel Variant in the <i>KIFBP</i> Gene.

Project description:Goldberg-Shprintzen syndrome (GOSHS) is characterized by microcephaly, developmental delay, dysmorphic features, Hirschsprung disease (HSCR), and brain anomalies. The kinesin family binding protein (KIFBP; MIM 60937) gene has been identified as the responsible gene of the syndrome. To date, 16 different biallelic KIFBP mutations have been identified in 34 patients with GOSHS. Even though most of these mutations are nonsense and frameshift, 3 missense mutations have also been described. Here, we report an 18-month-old patient with microcephaly, developmental delay, dysmorphic features and HSCR. Exome analysis was performed to clarify the etiology of the clinical features. A previously unreported homozygous c.1723delC (p.H575Ifs*19) variant was detected in the last exon 7 of KIFBP which led to GOSHS. According to our findings, we suggest that this mutation expands mutational databases and contributes to the understanding of the phenotypic features of the syndrome.

| S-EPMC8339512 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data