Hyperinsulinemic hypoglycemia in Beckwith–Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan

Abstract

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Sotos Syndrome Presenting with Neonatal Hyperinsulinaemic Hypoglycaemia, Extensive Thrombosis, and Multisystem Involvement

“…The initial screen for hypoglycaemia performed on day 3 of life showed the presence of inappropriately detectable insulin and C-Peptide, coupled with low non-esterified fatty acids and beta-hydroxybutyrate, leading to the diagnosis of CHI. The extended metabolic investigations and the counter-regulatory hormones were normal ( Table 1) over the last decade neonatal CHI has been increasingly described in this condition [3][4][5] with a recent Japanese national survey documenting CHI in 9/88 (10.2%) children with SoS and therefore suggesting that this is not an uncommon presenting feature of this condition [11]. The detailed clinical characteristics and biochemical mechanisms of CHI in SoS have not yet been well characterized.…”

“…Hence, the diagnosis of SoS was not clinically suspected and was only revealed by rapid WGS. In a Japanese case series, the majority of SoS patients presented with early hypoglycaemia (within < 3 hours of life) with only 2/9 requiring diazoxide and only 1/9 needing treatment for > 2 months [11]. In another study from the same group, 5/5 SoS patients were treated with intravenous glucose infusion at a maximum rate of 4.6-11.0 mg/kg/min for 12-49 days.…”

“…Asphyxia seems to be a common feature (33%) in syndromic forms of CHI [11], and hence it has been suggested that perinatal stress might contribute to the onset of hypoglycaemia [14]. However, not all children with SoS and CHI had asphyxia at birth and it has been hypothesized that disorders of NSD1 itself may cause abnormal secretion of insulin [3,4], although abnormalities in other genes responsible for the onset of CHI cannot be excluded.…”

Neonatal Hypoglycemia

“…CHH has been described in other diseases and syndromes, including congenital hypothyroidism [29], Sotos syndrome [4], Costello syndrome [21], Donohue syndrome [63], and Kabuki syndrome [62].…”

Giant umbilical cord and hypoglycemia in an infant with Proteus syndrome

“…Neonatal hyperinsulinemic hypoglycemia occurs in overgrowth syndromes, such as the Beckwith-Wiedemann and Sotos syndromes (Toda et al, 2017). Recently, hypoglycemia has been reported in patients with PIK3CA-and CCND-associated segmental overgrowth (McDermott et al, 2018).…”