Stories about: genetic syndromes

From mice to humans: Genetic syndromes may be key to finding autism treatment

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Boy and a mouse eye-to-eye
(Aliaksei Lasevich/stock.adobe.com)

A beautiful, happy little girl, Emma is the apple of her parents’ eyes and adored by her older sister. The only aspect of her day that is different from any other 6-month-old’s is the medicine she receives twice a day as part of a clinical trial for tuberous sclerosis complex (TSC).

Emma’s mother was just 20 weeks pregnant when she first heard the words “tuberous sclerosis,” a rare genetic condition that causes tumors to grow in various organs of the body. Prenatal imaging showed multiple benign tumors in Emma’s heart.

Emma displays no symptoms of her disease, except for random “spikes” on her electroencephalogram (EEG) picked up by her doctors at Boston Children’s Hospital. The medication she is receiving is part of the Preventing Epilepsy Using Vigabatrin in Infants with TSC (PREVeNT) trial. Her mother desperately hopes it is the active antiepileptic drug, vigabatrin, rather than placebo. …

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Clinical drug trial seeks to avoid liver transplant for LAL deficiency

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(Image courtesy Ed Neilan)

neilan_edward_dsc9139Second in a two-part series on metabolic liver disease. Read part 1.

According to the American Liver Foundation, about 1 in 10 Americans have some form of liver disease. One rare, under-recognized disorder, lysosomal acid lipase (LAL) deficiency, can fly under the radar until it becomes life-threatening, often requiring a liver transplant. LAL deficiency currently has no specific treatment, but that may change thanks to combined expertise in genetics, metabolism and hepatology.

In recent years, Boston Children’s Hospital’s Director of Hepatology, Maureen Jonas, MD, and the Metabolism Program’s Edward Neilan, MD, PhD, diagnosed three children with LAL deficiency. All three are now enrolled in the first international LAL deficiency clinical trial, with Neilan serving as Boston Children’s principal investigator.

“LAL deficiency is currently under-diagnosed,” Neilan says. “We think the disease is more common than doctors have thought and now, with a treatment in trial, it is of greater importance to identify those patients so they may have better outcomes.” …

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PVNH: Could this genetic disorder have a ‘butterfly’ effect?

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The butterfly effect is defined as “the sensitive dependence on initial conditions, where a small change at one place in a deterministic nonlinear system can result in large differences to a later state.” In medicine, the identification of a rare disease or a genetic mutation may provide insights that spread well beyond the initial discovery.

And in genetics, scientists are learning just how widespread the effects are for mutations in one gene: filaminA (FLNA).

FLNA is a common cause of periventricular nodular heterotopia (PVNH), a disorder of neuronal migration during brain development. The syndrome was first described by the late Peter Huttenlocher, MD, and the gene was identified by Christopher Walsh, MD, PhD, of Boston Children’s Hospital.

In normal brain development, neurons form in the periventricular region, located around fluid-filled ventricles near the brain’s center, then migrate outward to form six onion-like layers. In PVNH, some neurons fail to migrate to their proper position and instead form clumps of gray matter around the ventricles. …

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Inherited autism mutations found via genomic sequencing in Mideast families

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Pedigree for a family with 4 children with autism
In this family with 4 children with autism, a combination of genetic mapping and whole-exome sequencing identified a mutation in SYNE1, a known gene never previously associated with autism.

Autism clearly runs in some families, yet few inherited genetic causes have been found. A major reason is that these causes are so varied that it’s hard to find enough people with a given mutation to establish a clear pattern. Now, three large Middle Eastern families with autism spectrum disorders (ASDs) have led the way to a few more mutations, potentially broadening the number of genetic tests available to families.

What’s fascinating is that the mutations, described earlier this week in Neuron, affect genes known to cause severe, often lethal genetic syndromes. Milder mutations in the same genes, found through genomic sequencing, primarily cause autism.

Researchers Tim Yu, MD, PhD, Maria Chahrour, PhD, and senior investigator Christopher Walsh, MD, PhD, of Boston Children’s Hospital, started with three large families that had two or more children with an ASD, in which the parents were first cousins. Cousin marriages are a common tradition in the Middle East that greatly facilitates the identification of inherited mutations—as does large family size. …

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