Levi Anthony is our third child, and our one and only son. He was born via scheduled cesarean section and arrived with a full head of dark hair and handsome Italian complexion. His oldest sister Hayden passed away 3.5 years before his birth, and his second sister, Paisley, was 2.5 years old when he was born.
After raising Hayden, our daughter with CRELD1, and Paisley, our neurotypical child, the signs were clear from the beginning with Levi. We couldn’t ignore his lack of eye contact or poor head control. We knew. In our deepest, saddest hearts we knew. Our son Levi, likely had the same epilepsy that took our Hayden from us. It was one of the darkest times in our lives.
Witnessing Hayden’s first myoclonic jerks was confusing, but we had hope we could stop them. “Fix her”. Cure her condition and she could live a normal life. Witnessing Levi’s first myoclonic jerks was like having the wind knocked out of you. Over and over again. We recognised this monster from day one, and we knew all too well the suffering and grief it leaves in its wake. What it could destroy. What it could take from us. But we weren’t going into this battle blindly this time. And we didn’t know it yet, but we weren’t going to battle alone either.
Levi’s myoclonic jerks started when he was three months of age. A month later we were airlifted to the local children’s hospital due to status epilepticus. We were admitted for a week and started his first medication. We adamantly demanded both a surgery date for a portacath and a prescription for cannabis oil (something we never got to try with Hayden).
A week after returning from hospital, I received a call from a genetics counsellor: they had isolated the gene that likely caused Levi’s epilepsy. They still had Hayden’s, my husbands and my blood on file, and compared all four of us. It was confirmed: my husband and I were carriers and had passed down the CRELD1 gene change to two of our three babies.
But there was more news - there was another little girl. She lived in Texas, and her mother was keen to talk with me. I couldn’t wait to connect with this family; our children’s paths were identical, even their facial characteristics were similar. It was surreal.
Levi struggled with uncontrolled daily seizures for the next year or so. We added two more medications and two more cannabis oils. We ruled out trying the ketogenic diet because we believed it was in part to blame for Hayden’s arrhythmia and cardiac arrest. Levi had been intubated numerous times and admitted to PICUs for weeks at a time. Viruses were the worst - a fever could create a seizure storm that would last hours.
Around the spring of 2020, Levi’s daily myoclonic jerks just stopped. He fell into a routine seizure pattern of generalized seizures lasting 2-10 minutes every 7-10 days; sometimes going as long as 23 days between seizures! He has multiple seizure types, each one scarier than the last, but we have pretty good control. He began to develop, gaining strength we never imagined. Passing inch stones we never thought he would. Maintaining eye contact longer than we could have ever hoped.
Levi celebrated his 4th birthday this past summer. We weren’t sure he’d see his 2nd birthday. We celebrated with all the joy in our hearts and all the love in our house. But for us, it was just another day; because with Levi, we celebrate every day this way.
levi's genetics results
Sequencing analysis has shown that Levi is compound heterozygous for the C.254_257delACAG likely Pathogenic Variant and the p.(C192Y) Variant of Uncertain Significance in the CRELD1 gene.
c.254_257delACAG: p.Asp85ValfsX6 in exom 2 in the CRELD1 gene (NM_015513.4). The normal sequence with the bases that are deleted in brackets is: AAAG(delACAG)gtaa, where upper case letters denote exonic sequence and lower case letters denote intronic sequence.
p.Cys192Tyr (TGT>TAT): c.575 G>A in exon 5 in the CRELD1 gene (NM_015513.4).
For this gene, 100% of the coding region was covered at a minimum of 10x. There is no indication of a multi-exon deletion/duplication involving this gene in the sequencing data.
Levi's mother and sibling Hayden are heterozygous for the c.254_257delACAG variant in the CRELD1 gene. Levi's father and sibling Hayden are heterozygous for the p.(C192Y) variant in the CRELD1 gene.
The c.254_257delACAG variant in the CRELD1 gene has not been reported previously as a pathogenic variant nor as a benign variant. The c.254_257delACAG variant causes a frameshift starting with codon Aspartic acid 85, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Asp85ValfsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.254_257delACAG variant is not observed in large population cohorts and is likely a pathogenic variant.
The C192Y variant in the CRELD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant. The C192Y variant is observed in 47/1266)) (0.037%) alleles from individuals of non-Finnish European background in large population cohorts, and no individuals are reported as homozygous. The C192Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret C192Y as a variant of uncertain significance.