Alternative titles; symbols
SNOMEDCT: 129635004; ORPHA: 64739; DO: 5425;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2p16.3 | Ovarian hyperstimulation syndrome | 608115 | Autosomal dominant | 3 | FSHR | 136435 |
A number sign (#) is used with this entry because of evidence that spontaneous ovarian hyperstimulation syndrome (OHSS) is caused by heterozygous mutation in the follicle-stimulating hormone receptor gene (FSHR; 136435) on chromosome 2p16.
Ovarian hyperstimulation syndrome most often occurs as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization; the incidence of severe forms ranges from 0.5 to 5% (Delvigne and Rozenberg, 2002). The clinical manifestations vary from abdominal distention and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of the syndrome, whether spontaneous or iatrogenic, include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis (Scully et al., 1998).
Kaiser (2003) reviewed the pathogenesis of ovarian hyperstimulation syndrome and the mechanism by which mutations in the FSH receptor result in the disorder, with explanatory diagrams.
In a 25-year-old woman of Moroccan origin who had 4 of 5 spontaneous pregnancies complicated by ovarian hyperstimulation syndrome, Vasseur et al. (2003) identified heterozygosity for a mutation in the FSHR gene (T449I; 136435.0008). Two of the patient's 4 sisters reported similar histories, and the T449I mutation was identified in both; T449I was not identified in 1 of the patient's unaffected sisters.
In a woman with spontaneous ovarian hyperstimulation syndrome, previously described by Olatunbosun et al. (1996), Smits et al. (2003) identified a heterozygous missense mutation in the FSHR gene (D567N; 136435.0009).
In a 21-year-old Turkish woman who developed OHSS in the first trimester of her first pregnancy, previously described by Cepni et al. (2006), De Leener et al. (2008) identified heterozygosity for a mutation in the FSHR gene (S128Y; 136435.0013). Her beta-HCG level was normal for a 3-month singleton pregnancy, and her TSH (see 118850) level was normal; her symptoms regressed during the second and third trimester with conservative medical treatment, and resolved postpartum.
Cepni, I., Erkan, S., Ocal, P., Ozturk, E. Spontaneous ovarian hyperstimulation syndrome presenting with acute abdomen. J. Postgrad. Med. 52: 154-155, 2006. [PubMed: 16679690]
De Leener, A., Caltabiano, G., Erkan, S., Idil, M., Vassart, G., Pardo, L., Costagliola, S. Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome. Hum. Mutat. 29: 91-98, 2008. [PubMed: 17721928] [Full Text: https://doi.org/10.1002/humu.20604]
Delvigne, A., Rozenberg, S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum. Reprod. Update 8: 559-577, 2002. [PubMed: 12498425] [Full Text: https://doi.org/10.1093/humupd/8.6.559]
Kaiser, U. B. The pathogenesis of the ovarian hyperstimulation syndrome. New Eng. J. Med. 349: 729-732, 2003. [PubMed: 12930924] [Full Text: https://doi.org/10.1056/NEJMp038106]
Olatunbosun, O. A., Gilliland, B., Brydon, L. A., Chizen, D. R., Pierson, R. A. Spontaneous ovarian hyperstimulation syndrome in four consecutive pregnancies. Clin. Exp. Obstet. Gynec. 23: 127-132, 1996. [PubMed: 8894317]
Scully, R. E., Young, R. H., Clement, P. B. Atlas of Tumor Pathology. Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament. Third Series. Fascicle 23. Washington, DC: Armed Forces Institute of Pathology , 1998. Pp. 424-426.
Smits, G., Olatunbosun, O., Delbaere, A., Pierson, R., Vassart, G., Costagliola, S. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. New Eng. J. Med. 349: 760-766, 2003. [PubMed: 12930928] [Full Text: https://doi.org/10.1056/NEJMoa030064]
Vasseur, C., Rodien, P., Beau, I., Desroches, A., Gerard, C., de Poncheville, L., Chaplot, S., Savagner, F., Croue, A., Mathieu, E., Lahlou, N., Descamps, P., Misrahi, M. A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome. New Eng. J. Med. 349: 753-759, 2003. [PubMed: 12930927] [Full Text: https://doi.org/10.1056/NEJMoa030065]