Introduction: We report the first known case of a child with mosaic Turner syndrome (TS) with ring X chromosome abnormality and Kabuki syndrome (KDM6A deletion) presenting with hypoglycaemia secondary to severe GH deficiency. Ring X Turners mosaic have the XIST locus, so the chromosome is inactivated, however the KDM6A gene deletion associated with Kabuki syndrome escapes X-inactivation as it is falls below the threshold required to manifest inactivation. This results in a more severe phenotype than Turners monosomy.
Case history: We describe a girl diagnosed antenatally with a lumbar myelomenigocele and spina bifida. She was born at term with intra-uterine growth restriction and noted to be dysmorphic. Karyotype confirmed Turners mosaic syndrome 46,XrX(p11;q13)(22)/45,X(8)arrXp22.33p11.2x1,Xp11.1q13.3x2-3,Xq13.3q28x1 with a small r(X). Her features were consistent with Kabuki syndrome. CGH array confirmed the known KDM6A deletion associated with Kabuki syndrome. She developed recurrent asymptomatic hypoglycaemia around the ages of 2025 weeks with concurrent gastroenteritis, which was resistant to treatment with standard TS dose GH therapy. She underwent formal pituitary assessment aged 18 months confirming severe GH deficiency.
Discussion: Children with TS develop postnatal short stature. They usually have normal GH levels but show end organ resistance to it. Hypoglycaemia has been associated with Kabuki syndrome from various aetiologies including GH deficiency. Two recent case reports describe children with combined Turner mosaic and Kabuki syndrome presenting with hyperinsulinaemic hypoglycaemia, but no reported cases due to severe GH deficiency alone. The combination of GH deficiency and end organ GH resistance is likely to have led to the severity and resistance to treatment seen in this case, which rectified on treatment with a high dose of GH given in two divided doses (0.07 mg/kg per day).
Conclusion: From this case, we recommend a low threshold for monitoring blood glucose levels in children with this phenotype and if evident, growth hormone provocation testing should be performed.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology