BabyScreen+ newborn screening

Gene: LAMP2

Green List (high evidence)

X-linked dominant genetic disorder characterized by cardiomyopathy, skeletal myopathy, and neurocognitive deficits
Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias. The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death. Males are typically more severely affected than females.

Early onset cardiomyoapthy and neurodevelopmental phenotype - reproductive utility to prevent multiple affected pregnancies. High-penetrance cardiomyopathy with high risk of arrhythmia and or transplant. Neurodevelopmental issues allow preparation and early childhood intervention.
- Ages of onset in Cohort studies and personal experience M 0.25–45 F2–58
- The family known to RCH/MMC is neonatal onset cardiomyopathy, symptomatic, potentially we should publish more formally, was presented at HGSA

International natural history study ongoing.
Expect therapy in next few years. Trials ongoing in Europe and US with therapy for CM and improvement in ND outcomes.
Rocket Pharmaceuticals Adeno-associated- vector-501 (RP-A501) (AAV9.LAMP2B), an investigational gene therapy product for DD and the first potential gene therapy for monogenic heart failure.

Created: 15 Feb 2023, 4:27 a.m. | Last Modified: 15 Feb 2023, 4:27 a.m.

Panel Version: 0.1865

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Childhood onset cardiomyopathy (Severe); Neuordevelopmental phenotype

I don't know

Treatment is currently symptomatic.

On watch list with regards to specific treatment/clinical trials.

Created: 29 Mar 2023, 2 a.m. | Last Modified: 29 Mar 2023, 2 a.m.

Panel Version: 0.2140

For review: age of onset is typically adolescence.

Created: 26 Sep 2022, 9:42 a.m. | Last Modified: 26 Sep 2022, 9:42 a.m.

Panel Version: 0.211

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Danon disease, MIM# 300257

Green List (high evidence)

Gene-disease association: well established

Onset:Childhood (average age 12y males and 19y females

Treatment: cardiomyopathy treatment, ? transplant

Created: 26 Sep 2022, 3:47 a.m. | Last Modified: 26 Sep 2022, 3:47 a.m.

Panel Version: 0.199

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Danon disease - cardiomyopathy, retinal disease, cognitive dysfunction