SCIENCE: CHILDREN DIE WITHOUT EXPLANATION
Genetics is finally giving us some answers.

Every year in the Unit­ed States, hun­dreds of chil­dren die for unde­ter­mined rea­sons, usu­al­ly while sleep­ing or at rest. Because of the way deaths are inves­ti­gat­ed and cer­ti­fied, it is dif­fi­cult to say how often this hap­pens. Accord­ing to some esti­mates, sev­er­al hun­dred chil­dren between the ages of 1 and 18 die sud­den­ly of unex­plained caus­es each year.

When the child is less than 12 months old, it is called sud­den infant death syn­drome (SIDS). Accord­ing to the CDC, 1,250 such deaths qual­i­fied in 2019, about three times the num­ber of sud­den unex­plained deaths in chil­dren (SUDC).

SIDS caus­es three times as many deaths as SUDC, but receives 20 times more research funding.

Lau­ra Gould has been work­ing for decades to change that. After los­ing her 15-month-old child in 1997, she co-found­ed the SUDC Reg­istry and Research Col­lab­o­ra­tive (SUDCRRC) with a neu­rol­o­gist at New York University.

By using the data­base to com­pare 124 mol­e­c­u­lar autop­sy results with the par­ents’ genet­ic data, the researchers have now revealed a poten­tial cause for some cas­es of SUDC.

In near­ly a dozen cas­es, the researchers iden­ti­fied eight genet­ic vari­ants linked to epilep­sy, car­diac arrhyth­mias and neu­rode­vel­op­men­tal disorders.

Six of the genet­ic vari­ants are known to be involved in cal­ci­um sig­nalling, which allows the heart mus­cle to con­tract and neu­rons to trig­ger messages.

In most cas­es, the par­ents of the deceased chil­dren did not show the same muta­tions, which means that they were not inher­it­ed but derived at random.

Accord­ing to the researchers, it is unlike­ly that a par­ent would have two chil­dren with the same lethal variant.

“Our study is the largest of its kind to date, the first to prove that there are spe­cif­ic genet­ic caus­es of SUDC, and the first to com­plete any part of the risk pic­ture,” says NYU neu­ro­sci­en­tist Richard Tsien.

“In addi­tion to pro­vid­ing com­fort to par­ents, new find­ings about the genet­ic changes involved will accu­mu­late over time, reveal the mech­a­nisms respon­si­ble and serve as the basis for new treat­ment approaches.”

The study specif­i­cal­ly looked for 137 genet­ic vari­ants linked to heart prob­lems and epilep­sy, as this appears to be the cause of most cas­es of SUDC.

Com­pared to the gen­er­al pop­u­la­tion, these vari­ants were ten times more like­ly to occur among SUDC cases.

But there are prob­a­bly oth­er expla­na­tions out there. The genet­ic vari­ants iden­ti­fied in the present study were found in only 9% of the cohort; more work needs to be done to under­stand what caus­es the major­i­ty of SUDC cases.

A sec­ond study, con­duct­ed by the same team of researchers, took the data fur­ther. This time they looked for 294 poten­tial­ly lethal genet­ic vari­ants in 352 cas­es of SUDC.

Among a sub­set of 73 cas­es, where parental data were also avail­able, the authors found 37 genet­ic vari­ants that are like­ly to be linked to neu­ro­log­i­cal, car­diac or sys­temic diseases.

The researchers note that the pres­ence of path­o­gen­ic gene vari­ants “does not in itself estab­lish causal­i­ty”, but their find­ings are a very promis­ing start not only to pro­vide bet­ter diag­no­sis and peace of mind to bereaved par­ents, but also to poten­tial­ly iden­ti­fy risk fac­tors that lead to SUDC before tragedy strikes.

“In addi­tion to pro­vid­ing com­fort to par­ents, fur­ther dis­cov­er­ies about the genet­ic changes involved will accu­mu­late over time, reveal­ing the mech­a­nisms responsible.