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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

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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.

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

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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.

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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.

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