Table 2

Summary of clinical, hormonal and imaging results

Case 1 (V-1, family A) FemaleCase 2 (V-2, family A) MaleCase 3 (IV-3, family B) Female
Clinical findings
Age at presentation15 years2 weeks14.5 years
Presenting symptomPrimary amenorrhoeaHypocalcaemic seizuresPrimary amenorrhoea
Other clinical abnormalities
 CardiacNormalVSD and right aortic archNormal
 KidneyAgenesis of left kidneyNormalNormal
 LungNormalBronchiectasis due to recurrent pneumoniaNormal
 HearingMild conductive high frequency hearing loss in left earNormalNormal
 Immune systemNormalT cell immune deficiencyNormal
 NeurologyTemporal epilepsyNormalNormal
Mild mental retardationMild mental retardationNormal
Height (cm) (at last visit)163 (0.33 SD)161 (−2.5 SD)158 (−0.7 SD)
Weight (kg) (at last visit)40.5 (−1.3 SD)43.3 (−4.4 SD)54 (0.3 SD)
Pubertal signs (at last visit)Tanner stage P5, B2*Tanner stage P5, testicular volume 3Tanner B3* P3*
Dysmorphic featuresElongated face, hypertelorism and long fingersThin face, vitiligo spot on forehead, narrow chest with small nipplesNone
Hormonal results
GnRH stimulation test
 Age (years)151814.5
 Basal LH (mIU/L)31.721.360
 Peak LH (mIU/L)12084.6NA
 Basal FSH (mIU/L)14646.894
 Peak FSH (mIU/L)>15080.4NA
Oestradiol (pmol/L)/testosterone (nmol/L)<18313.9<183
ACTH stimulation test
 Basal cortisol (nmol/L)358378NA
 Peak cortisol (nmol/L)613616NA
AMH (ng/mL)Undetectable3.06NA
Imaging
SonographyNo ovary and no uterus (15, 17, 18 years)Homogeneous testis in 2.6 cm volume (19 years)No ovaries , small prepubertal uterus length 5 cm (14.5 years)
No ovary, 6 mm long uterus with 4 mm mucosa (20 years)
MRI
 PelvicNo ovary or uterus and rudimentary vagina (17 years)NA
 BrainNormalNDNA
Genetic evaluation
Karyotype46, XX46, XY46, XX
22q11delNoYesNo
MCM8 gene mutationc.1954-1G>A/c.1954-1G>Ac.1954-1G>A/c.1954-1G>Ac.1469-1470insTA/c.1469-1470insTA
  • *On hormonal replacement therapy.

  • Normal range: LH (mIU/L), male: 1.5–9.3, female: 1.9–12.5; FSH (mIU/L), male: 1.4–18, female: 2.5–10; testosterone (nmol/L): 8.3–28.8; oestradiol (pmol/L): 40.4–605.5; AMH (ng/mL), male: 0.7–19, female: 0.9–9.5.

  • ACTH, adrenocorticotropic hormone; AMH, anti-Müllerian hormone; FSH, follicle stimulating hormone; GnRH, gonadotropin releasing hormone; LH, luteinising hormone; NA, not available; ND, not detectable; VSD, ventricular septal defect.