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 ova ry syndrome (PCOS). The observation of familial aggregation of PCOS is cons istent with a genetic component of this disorder. We report on a 21-year-ol d woman with menstrual irregularity, hirsutism, elevated serum androgen lev els and polycystic ovarian morphology on ultrasonography, meeting the diagn ostic criteria of PCOS. A cytogenetic investigation was performed because o f a congenital heart defect, craniofacial anomalies in infancy (quadricepha ly with protruding forehead, flat nasal bridge, low set ears with attached earlobes, small mouth, high arched palate with submucous palatal cleft, ret rognathia), broad neck, motor and speech developmental delay. Chromosomal a nalysis revealed an unbalanced interstitial deletion of one of the chromoso mes 11 [del (11) (q21q23.1)]. Interstitial deletions of the long arm of chr omosome II have been reported in at least 18 patients. Candidate genes for PCOS have not been suspected at this chromosomal location so far. Follistat in 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 pr ogesterone receptor concentration is associated with retardation of endomet rial development. A disturbance of the hypothalamic-pituitary gonadal axis, due to a reduction of hypothalamic and pituitary progesterone receptors mi ght be a component in the etiology of PCOS.