1 Introduction

The Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism deficiency and an anosmia or hyposmia secondary to the olfactory bulbs hypoplasia or aplasia (Jebasingh et al., 2015; Dodé et al., 2009; Gurdasani et al., 2008).

2 Case report

We report the case of a female patient of 27 years with no particular family history and who consulted for primary amenorrhea. The clinical examination revealed a female morphotype with eunuchoid appearance. The patient was immature and had anosmia, a right ptosis and hearing loss right. Size = 1.66 m, weight = 51 kg, BMI = 18.50 kg/m². Laboratory tests: FSH- 0.67 mIU/L, LH-0.05 mIU/L, Estradiol- 17 pg/ml (gonadotropin deficiency), basic cortisol-264.72 nmol/L, ACTH-6 pg/ml (adrenocorticotropic deficiency), FT4-6.20 pmol/L, TSHus-3.11 μIU/L (thyreotropic deficiency), PRL=4.02 ng/ml. The Karyotype was 46XX. The hypothalamic pituitary MRI revealed an agenesis of the olfactory bulbs (Figure 1). An abdominal ultrasound performed to search an associated renal malformation and completed with a pelvic MRI found a uterine agenesis (Figure 2), atrophic ovaries (right ovary-1 cm³ and left ovary-2 cm³, Figure 3 and Figure 4 respectively) and a malrotation of a small right kidney (Figure 5). The echocardiography didn’t show any anomaly. Our treatment consisted in a hormonal replacement therapy.

Figure 1 The hypothalamic pituitary MRI

Figure 2 The uterine ultrasound

Figure 3 The right ovarian ultrasound

Figure 4 The left ovarian ultrasound

Figure 5 The kidney ultrasound

3 Discussion

The KS is rare and transmitted in three ways: X-linked recessive, autosomal dominant or rarely autosomal recessive. However, sporadic cases are far the most common. It is not uncommon to find as part of the syndrome, urinary malformations, syndactilia, and unilateral deafness. The incidence is approximately 1 in 8000 males and 1 in 40,000 females (Dodé et al. 2009). It is due to a defect in embryonic migration of GnRH neurons synthesizing and the olfactory system, which normally migrate by following the path of the olfactory nerves olfactory placode to the hypothalamus leading to agenesis of the olfactory bulb and gonadotropin deficiency (Shetty et al., 2015). Our patient developed a KS with a panhypopituitarism and a uterine agenesis. To our knowledge, there has not been, to date, reported cases of the KS with a uterine agenesis. However, some authors (Brandenberger et al., 1994) reported, in 2 patients, treated for infertility, an associated malformation of the uterus (a horned uterus and a uterine hypoplasia). The chosen explanation was likely an underlying genetic defect related to organogenesis. Moreover, Raivio looked for common genetic origins between the KS, the anterior pituitary deficit and the septo-optic dysplasia. His results went in the sense of a significant genetic overlap between states that affect the development of the midline in the human brain (Raivio et al., 2012)

4 Conclusion

All the abnormalities associated with the KS derive from developmental disorders during the organogenesis. Many genes are involved in the pathogenesis. In the present state of our knowledge, there were no reported cases of KS with panhypopituitarism and uterine agenesis. It seems justified to us to seek all the defects associated with KS.

Author’s contributions

By signing this letter each of us acknowledges that she or he participated sufficiently in the work to take public responsibility for it.

References

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http://dx.doi.org/10.7860/jcdr/2015/11761.5777