Association of polycystic ovary syndrome with an interstitial deletion of the long arm of chromosome 11 [del(11)(q21q23.1)]

Several pathways have been implicated in the etiology of the polycystic ovary syndrome (PCOS). The observation of familial aggregation of PCOS is consistent with a genetic component of this disorder. We report on a 21-year-old woman with menstrual irregularity, hirsutism, elevated serum androgen levels and polycystic ovarian morphology on ultrasonography, meeting the diagnostic criteria of PCOS. A cytogenetic investigation was performed because of a congenital heart defect, craniofacial anomalies in infancy (quadricephaly with protruding forehead, flat nasal bridge, low set ears with attached earlobes, small mouth, high arched palate with submucous palatal cleft, retrognathia), broad neck, motor and speech developmental delay. Chromosomal analysis revealed an unbalanced interstitial deletion of one of the chromosomes 11 [del (11) (q21q23.1)]. Interstitial deletions of the long arm of chromosome II have been reported in at least 18 patients. Candidate genes for PCOS have not been suspected at this chromosomal location so far. Follistatin and CYP11A, the genes with the strongest evidence for linkage with PCOS, are located on chromosomes 5 and 15. In the chromosomal region deleted in our patient a progesterone receptor gene is located in band q22. Lowered progesterone receptor concentration is associated with retardation of endometrial development. A disturbance of the hypothalamic-pituitary gonadal axis, due to a reduction of hypothalamic and pituitary progesterone receptors might be a component in the etiology of PCOS.