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Case Reports
. 2020 Sep 18;46(1):136.
doi: 10.1186/s13052-020-00902-8.

Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation

Ettore Piro  1 , Ingrid Anne Mandy Schierz  2 , Vincenzo Antona  2 , Maria Pia Pappalardo  3 , Mario Giuffrè  2 , Gregorio Serra  2 , Giovanni Corsello  2
Affiliations
Case Reports

Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation

Ettore Piro et al. Ital J Pediatr. .

Abstract

Background: Persistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.

Patient presentation: We report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.

Conclusions: Kabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

Keywords: Facial dysmorphism; Hyperinsulinism; Neonatal hypoglycemia; Neonatal hypotonia; Nervous system malformation.

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Conflict of interest statement

Not applicable.

Figures

Fig. 1
Fig. 1
Brain ultrasound. a. Axial view through the mastoid fontanel: enlarged fourth ventricle (black arrow). b. Sagittal view through the anterior fontanel: cerebellar vermis hypoplasia with secondary enlarged of the fourth ventricle (black arrow) and enlarged cisterna magna (white arrow)
Fig. 2
Fig. 2
Dysmorphic facial features suggestive of Kabuki syndrome
Fig. 3
Fig. 3
T2 weighted FSE Brain Magnetic Resonance Imaging. a. Sagittal scan: enlarged fourth ventricle (black arrow), and cisterna magna with inferior vermian hypoplasia (white arrow). b. Coronal scan: Enlarged vallecula cerebelli and hypoplasia of the cerebellar hemispheres (black arrow)
See this image and copyright information in PMC

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