MYRF mutation leads to a single manifestation of sexual development and mimics partial androgen insensitivity syndrome: a case report and literature review

Abstract

Objective

To highlight the challenges in diagnosing 46, XY disorder of sex development related to MYRF mutation.

Methods

We present an unusual case of a 12-year-old female child came for enlargement of clitoris and initially diagnosed as partial androgen insensitivity syndrome (AIS).

Results

On examination, the patient’s vulva was found virilized with 3cm-long clitoris. Her peripheral blood karyotype was 46, XY. The ultrasound showed an empty pelvis and hormone results confirmed hyperandrogenism. Therefore, the partial AIS was suspected, but the following whole exon sequencing indicates a pathological missense mutation in MYRF. Further investigation and surgery did not reveal any brain, heart, lung or diaphragm lesions related to MYRF, but only maldeveloped internal genitalia and a persistent urachus. Her serum testosterone dropped to normal after surgical removal of the remaining ipsilateral testis and epididymitis without spermatogenesis as shown by pathology.

Conclusion

Due to the karyotype, hyperandrogenism, empty pelvis but a virilism after puberty, the patient was initially diagnosed as partial AIS. This misleading clinical diagnose will not be verified as the MYRF mutation if without the whole exon sequencing, particularly in the absence of obvious brain, heart, lung and diaphragm lesions as in this case.

Keywords:

• Cardiac-urogenital-diaphragm-lung (CUDL) syndrome
• disorder of sex development (DSD)
• myelin regulatory factor (MYRF)
• partial androgen insensitivity syndrome

Acknowledgements

We are grateful to the patient’s family who agree for the report of this case.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Peking Union Medical College Hospital. Written informed consent was obtained from the couple (the patient’s parents) mentioned in this article for publication of medical history and images related to this case.

Author contribution

ZDD collected raw data and wrote the main manuscript text; TQJ was responsible for the conceptualization, design and funding acquisition. All authors reviewed the manuscript and agreed for publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or used during the study appear in the submitted article. The dataset of gene mutation is in ClinVar (www.ncbi.nlm.nih.gov/clinvar) and the accession number is SUB13949291.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China and National High-level Hospital Clinical Research Funding [grant number 2022-PUMCH-B-075].