Delayed Puberty and Anosmia in CHARGE Syndrome: A Case Report




anosmia, delayed puberty, CHARGE syndrome


A 26-year-old lady presented to the paediatric clinic at 11 years of age with poor growth. The detection of delayed
puberty, anosmia, coloboma and hearing impairment led to a diagnosis of CHARGE syndrome. This was confirmed
by a heterogenous de novo pathogenic variant c.6955C >T:p.(Arg2319Cys) detected in the CHD7 gene. Detailed
assessment, including olfaction, ophthalmic and auditory examination should be part of the evaluation framework in children with delayed growth and puberty.


Download data is not yet available.

Author Biographies

Yee Lin Lee, Universiti Putra Malaysia

Department of Paediatrics

Luke Toh, KK Women's and Children's Hospital

Department of Diagnostic and Interventional Imaging

Fabian Yap, KK Women's and Children Hospital

Department of Paediatric Endocrinology


Vissers L. E., van Ravenswaaij C. M., Admiraal R et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36(9):955–7.

Verloes A. Updated diagnostic criteria for CHARGE syndrome: A proposal. Am J Med Genetics Part A, 2005;133A(3):306–8.

Hale CL, Niederriter AN, Green GE, et al. Atypical phenotype associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria. Am J Med Genet A. 2016;170A(2):344–54.

Sedlmeyer Il, Palmert MR. Delayed puberty: Analysis of a large case series from an academic center. J Clin Endocrinol Metab. 2002;87(4):1613-20.

Manning BJ, Yusufzai T. The ATP-dependent chromatin remodeling enzymes CHD6, CHD7, and CHD8 exhibit distinct nucleosome binding and remodeling activities. J Biol Chem. 2017;292(28):11927-36.

He D, Marie C, Zhao C et al. Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination. Nat Neurosci. 2016;19(5):678–89.

Sanlaville D, Etchevers HC, Gonzales M, et al. Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet, 2006;43(3):211–7.

Bergman JE., Janssen N, Hoefsloot LH. et al (2011). CHD7 mutations and CHARGE syndrome: The clinical implications of an expanding phenotype. J Med Genet. 2011; 48:334-42.

Jongmans MCJ, van Ravenswaaij-Arts CMA, Pitteloud N, et al. CHD7 mutations in patients initially diagnosed with Kallmann syndrome – the clinical overlap with CHARGE syndrome. Clin Genet. 2009;75(1):65–71.

Bergman JEH, de Ronde W, Jongmans MCJ, et al. The results of CHD7 analysis in clinically well-characterized patients with Kallmann syndrome. J Clin Endocrinol Metab. 2012;97(5):E858–62.

Dode C, Hardeline JP. Kallman syndrome. Eur J Hum Genet. 2009;17(2):139-46.

Vesseur AC, Verbist BM, Westerlaan HE, et al. CT findings of the temporal bone in CHARGE syndrome: Aspects of importance in cochlear implant surgery. Eur Arch Otorhinolaryngol. 2016;273(12):4225–40.

Bauer PW, Wippold FJ II, Goldin J, Lusk RP. Cochlear implantation in children with CHARGE association. Arch Otolaryngol Head Neck Surg. 2002;128(9):1013–7.

Trider CL, Arra-Robar A, van Ravenswaaij-Arts, Blake K. Developing a CHARGE syndrome checklist: Health supervision across the lifespan (from head to toe). Am J Med Genet A. 2017;173(3):684–91.

Boehm U, Bouloux PM, Dattani MT, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism–pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547–64.



How to Cite

Lee, Y. L., Toh, L., & Yap, F. (2020). Delayed Puberty and Anosmia in CHARGE Syndrome: A Case Report. Journal of the ASEAN Federation of Endocrine Societies, 35(1), 122–124.



Case Reports