February 2026 Research Update

This month sharpened the picture of CHI as part of some genetic syndromes

Across two syndrome-focused reports, CHI showed up as an important complication in certain genetic conditions, and specific gene changes seemed to track with who developed low blood sugar. In Kabuki syndrome, CHI was fairly common in this small cohort and clustered with a particular type and location of KMT2D gene change. In CHARGE syndrome, a single reported child had clear hyperinsulinemic hypoglycemia that responded to diazoxide even though common CHI gene testing was negative, raising the possibility that CHI can be part of CHARGE for some families. [1] [2]

In Kabuki syndrome, neonatal low blood sugar was seen in about one-third of patients, and 5 of 18 had CHI; 3 had persistent CHI that needed medicine. All patients with CHI carried KMT2D variants, and in this cohort the hypoglycemia cases were linked to truncating (gene-shortening) variants in the later (C-terminal) part of KMT2D rather than missense variants. For families, this kind of pattern may help explain why CHI happens in some children with Kabuki syndrome and not others, although the study was small and retrospective. [1]

In the CHARGE syndrome case, hyperinsulinemic hypoglycemia was confirmed using critical blood tests during hypoglycemia and a glucagon response, and the child maintained normal sugars on diazoxide during follow-up into early childhood. Testing did not find a disease-causing variant in a panel of 22 known HI genes, but a pathogenic CHD7 variant confirmed CHARGE syndrome, so the report highlights an unresolved question about how CHD7 might connect to insulin regulation. As a single case, it cannot show how often this happens, but it adds another detailed example for future studies to compare. [2]

What this means for patients and caregivers

These reports mainly add understanding rather than changing day-to-day CHI care. They support the idea that CHI can be part of some genetic syndromes, and that the exact gene change may matter for who is at higher risk. What remains uncertain is how common CHI is in CHARGE syndrome and whether the Kabuki pattern holds in larger, more diverse groups, but this month made the gene-and-syndrome connection feel more specific and testable. [1] [2]

A clearer link between BWS genetics and how severe hyperinsulinism can be

Two studies in Beckwith-Wiedemann syndrome (BWS) lined up on a shared message: the genetic subtype of BWS helps explain why hyperinsulinism is mild for some children and severe for others. In routine-care data, certain BWS genetic patterns were tied to greater need for intensive sugar support and surgery, while others were more often diazoxide responsive. Lab work on pancreatic tissue from infants who needed surgery adds biologic detail, showing insulin secretion changes that may help explain why BWS-related CHI does not always behave like classic KATP-channel CHI. [3] [4]

In the 85-child BWS cohort, children with paternal uniparental disomy of chromosome 11 (pUPD11) were more likely to have more severe hyperinsulinism measures and to need pancreatic surgery. The risk of more severe disease appeared especially higher when the pUPD11 region extended into the KATP gene area and when ABCC8 or KCNJ11 variants were also present, while IC2 LOM, IC1 GOM, and CDKN1C groups were usually diazoxide responsive and less likely to need surgery. For families, this makes the differences in BWS-related CHI feel less random and more connected to the underlying genetic subtype. [3]

In pancreatic islets taken from infants with BWS-CHI who required surgery, the islets showed elevated calcium levels and released insulin when exposed to a physiologic mix of amino acids. Many islets still responded to glucose and to glyburide, and gene expression testing found reduced KCNQ1 expression compared with normal islets. This points to BWS-CHI having multiple drivers of extra insulin release, not just one blocked pathway, which may help explain why severity and treatment response can vary. [4]

What this means for patients and caregivers

For families affected by BWS and CHI, this month strengthens the idea that genetics can help anticipate the range of severity, although these findings still come from single-center experiences and lab studies. The cohort results may matter sooner because they connect BWS subtypes to real-world outcomes like diazoxide responsiveness and surgery, while the lab findings mainly matter for research because they explain possible biological reasons behind those differences. What remains uncertain is how well these patterns apply across different hospitals and populations, and which specific biology best predicts an individual child course. [3] [4]

Both reassurance and caution about medicines appeared this month

This month included two very different medication-related signals: a safety-focused look at diazoxide in routine care and an early discussion of a targeted drug idea (alpelisib) for severe, resistant CHI. The diazoxide study suggests pulmonary hypertension was uncommon overall but concentrated in a specific high-risk subgroup. The alpelisib letter describes preliminary observations of rapid glucose stabilization in severe cases, while emphasizing that long-term safety and stronger evidence are still needed. [5] [6]

In a 65-child diazoxide-treated cohort, pulmonary hypertension occurred in 3 children (5%), and all cases were in children with trisomy 13; lower birth weight also differed between groups. The authors estimated a much higher probability of pulmonary hypertension in trisomy 13 than in children without trisomy 13, and they reported cardiac failure-related adverse drug reactions in some children. For families, the main point is that risk may not be evenly distributed across all children who receive diazoxide, though the study was small and from one center. [5]

A letter proposed alpelisib (a PI3K-alpha inhibitor, used as a targeted drug in other conditions) as a mechanism-based approach for infants with severe, drug-resistant CHI. The authors described preliminary observations of improved glucose stability and fewer hospitalizations, and they highlighted the need for early-phase studies and longer follow-up for safety. This is an early signal rather than proof of benefit, but it shows active effort to expand options for the most difficult-to-control CHI. [6]

What this means for patients and caregivers

The diazoxide findings may matter now mainly as better understanding of who might face higher risks, especially in children with trisomy 13, while the overall frequency in this report was low. The alpelisib discussion is mainly research at this stage, because it is based on preliminary observations and does not yet define who benefits or what long-term side effects might look like. Together, these studies add to a more nuanced picture: established medicines have subgroup-specific safety questions, and new targeted approaches are being explored for severe, resistant CHI. [5] [6]