IMPE Abstracts

Background: Kabuki syndrome (KS) is a rare malformation and disability syndrome, associated with congenital hyperinsulinism (CHI) in 0.3-4%. Whereas CHI may be the overt already from day one of life, the median age at KS diagnosis is 11-16 months.

Methods: Case report

Results: A term-born girl, birth weight 4550 g had unexpected hypoglycemia 1.8 mmol/L (32 mg/dL) day one of life with need of i.v. glucose 8.4 mg/kg/min. Day 3 of life, plasma insulin was not suppressed, 49 (ref. 18-173) pmol/L, at plasma glucose 2.4 mmol/L (43 mg/dL), indicating hyperinsulinism. Diazoxide treatment was effective in preventing hypoglycemia, but could not be tapered. Kabuki Syndrome was clinically suspected age at age 3 weeks due to CHI, a persisting eating disorder with unsuccessful trials of tube feeding discontinuation, generalized hypotonia, and syndromic features including discrete fetal finger and toe pads, long palpebral fissures and long eye lashes. Abnormalities of the eyebrows, nose, or ears were not overt in the neonatal period. In addition, ultrasound revealed horseshoe kidneys, while echocardiography showed no other abnormality than mild hypertrophic myocardia, typically seen in CHI. Rapid trio genome sequencing with an extended CHI bioinformatics panel showed a known, de novo KMT2D DNA variant c.16438_16441delAACT, p.(Asn5480Valfs*6), confirming KS. A gastric tube was installed to ensure enteral feeding. Age 2½ months, a diminished head circumference growth 0.36 cm/week to 38 cm was followed by a CT scan of the skull, revealing premature closure of the metopic suture; no signs of increased intracerebral pressure. Generalized hypotonia persisted and a narrow forehead and arched eyebrows with lateral notching had now emerged. Diazoxide was still needed in a dose of 11 mg/kg/day. Surgery for premature craniosynostosis was scheduled.

Conclusion: A high suspicion of KS in CHI and extended genetic investigations may lead to early diagnosis of KS already at age 1-2 months. The early KS diagnosis is helpful in identifying and managing the syndromic aspects of KS.