Deviation of paradigmatic mutations found in Shprintzen-Goldberg syndrome


  • Arnab Nandy Department of Paediatric Medicine, North Bengal Medical College, Darjeeling, West Bengal, India
  • Sankar K. Das Department of Paediatric Medicine, North Bengal Medical College, Darjeeling, West Bengal, India
  • Sumit Roy Department of Paediatric Medicine, North Bengal Medical College, Darjeeling, West Bengal, India
  • Shreyasi Das Department of Paediatric Medicine, North Bengal Medical College, Darjeeling, West Bengal, India



Craniofacial abnormality, Craniosynostosis, Germline mutation, Marfanoid habitus, Shprintzen-Goldberg Craniosynostosis syndrome, Undescended testis


Shprintzen-Goldberg (S-G) Syndrome known as rare congenital connective tissue disorder where craniosynostosis and marfanoid habitus found to be the usual presentation. Craniofacial dysmorphism with multi-organ involvement documented to be amongst prominent features of this syndrome. Case characteristics is five-month-old male infant with craniosynostosis, and motor developmental delay was evaluated for congenital connective tissue disorder. Dysmorphic craniofacial features like dolichocephaly, triangular forehead, ocular hypertelorism, micrognathia and retrognathia were noticed besides congenital umbilical hernia, empty scrotal sac, clinodactyly with long slender fingers, hyper-mobile joints, hypotonia. Subsequent investigations revealed normal male karyotype (46, XY) while genetic analysis depicted missense mutations in six different genes. Conventionally, mutation in SKI gene reported for its’ associated with S-G syndrome where dysregulation of TGF-β signaling was discussed as the primary reason. In the present case discussed here, it was found to have polygenic mutational association where few novel genetic mutations were seen.


Greally MT, Carey JC, Milewicz DM, Hudgins L, Goldberg RB, Shprintzen RJ, et al. Shprintzen‐Goldberg syndrome: A clinical analysis. Am J Med Genetics. 1998;76(3):202-12.

Shah B, Sahu S, Kalakoti P, Yadav S, Syed MA, Bhattad VB, et al. Shprintzen-Goldberg syndrome presenting as umbilical hernia in an Indian child. Australasian Med J. 2014;7(2):51.

Topouzelis N, Markovitsi E, Antoniades K. Shprintzen-Goldberg syndrome: case report. Cleft Palate Craniofac J. 2003;40(4):433-6.

Akutsu K, Morisaki H, Takeshita S, Sakamoto S, Tamori Y, Yoshimuta T, et al. Phenotypic heterogeneity of Marfan-like connective tissue disorders associated with mutations in the transforming growth factor-β receptor genes. Circulat J. 2007;71(8):1305-9.

Robinson PN, Neumann LM, Demuth S, Enders H, Jung U, König R, et al. Shprintzen–Goldberg syndrome: fourteen new patients and a clinical analysis. Am J Med Genetics Part A. 2005;135(3):251-62.

Schepers D, Doyle AJ, Oswald G, Sparks E, Myers L, Willems PJ, et al. The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen–Goldberg syndrome. Europ J Human Genetics. 2015;23(2):224.

Shprintzen RJ, Goldberg RB. A recurrent pattern syndrome of craniosynostosis associated with arachnodactyly and abdominal hernias. J Cranio Genetics Develop Biol. 1982;2(1):65-74.

Yadav S, Rawal G. Shprintzen-Goldberg syndrome: a rare disorder. Pan Afr Med J. 2016;23:227.

Saito T, Nakane T, Yagasaki H, Naito A, Sugita K. Shprintzen-Goldberg syndrome associated with first cervical vertebra defects. Pediatr Int. 2017;59(10):1098-100.

Kimura N, Inaba Y, Kameyama K, Shimizu H. Thoraco-abdominal aortic aneurysm rupture in a patient with Shprintzen-Goldberg syndrome. Inte Cardio Thoracic Surg. 2018;26(6):1039-40.

Schwartz M. Rho signalling at a glance. J Cell Sci. 2004;117(23):5457-8.

Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biology. 2003;13(1):13-22.

Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, et al. Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nature Genetics. 2012;44(11):1249.

Pauliks LB, Chan KC, Lorts A, Elias ER, Cayre RO, Valdes-Cruz LM. Shprintzen‐Goldberg Syndrome With Tetralogy of Fallot and Subvalvar Aortic Stenosis. J Ultrasound Med. 2005;24(5):703-6.

van Steensel MA, van Geel M, Parren LJ, Schrander- Stumpel CT, Marcus-Soekarman D. Shprintzen-Goldberg syndrome associated with a novel missense mutation in TGFBR2. Exp Dermatol. 2008;17:362-5.

Verstraeten A, Alaerts M, Van Laer L, Loeys B. Marfan syndrome and related disorders: 25 years of gene discovery. Human Mutation. 2016 Jun;37(6):524-31.

Al Kaissi A, Marrakchi Z, Nassib NM, Hofstaetter J, Grill F, Ganger R, et al. Craniosynostosis, Scheuermann's disease, and intellectual disability resembling Shprintzen-Goldberg syndrome: a report on a family over 4 generations: Case Report. Med. 2017;96(12).

Hoffjan S. Genetic dissection of Marfan syndrome and related connective tissue disorders: an update 2012. Mol Syndromol. 2012;3(2):47-58.

Bari A, Sadaqat N, Nawaz N, Bano I. Shprintzen-Goldberg Syndrome: A Rare Disorder. J College of Physicians and Surgeons-Pakistan: JCPSP. 2019;29(6):41-2.

Saal HM, Bulas DI, Allen JF, Vezina LG, Walton D, Rosenbaum KN. Patient with craniosynostosis and marfanoid phenotype (Shprintzen‐Goldberg syndrome) and cloverleaf skull. Am J Med Genetics. 1995;57(4):573-8.






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