Beginning of the story
A boy was born at 35 weeks of gestation from healthy, nonconsanguineous parents. He weighed 3.5kg at birth, which was a little heavier than average.
Another boy was born at 39 weeks of gestation from healthy, nonconsanguineous parents, with 3.2kg weight at birth.
First boy’s presenting features
When born, the first boy had a swollen body. He was also presenting sparse scalp hair, sparse eyebrow, webbed neck, hypertelorism, low-set dysplastic ear, generalized hypotonia.
Unsuccessful first examinations
To find the cause of his conditions, brain ultrasonography, abdominal ultrasonography, echocardiography, and chromosome analysis were conducted. However, the results were confirmed as normal.
Whole exome sequencing to find the cause
The doctor knew that there must be a cause somewhere in his genome. The doctor requested whole exome sequencing(WES) to 3billion when the boy was only 20 days after birth.
After a few weeks, results for him came out. The sequencing and interpretation found a de novo genetic variant in the BRAF gene.
Different phenotypes of the second boy
Unlike the first boy, this boy was relatively healthy but not properly gaining weight. Because his presenting features were vague and only developmental delay was suspected, tests for Fragile X syndrome, PWS, MECP2, DMPK were conducted.
However, all of the results were shown negative.
Late use of WES
This boy started an infantile spasm at 15 months of age and showed relative macrocephaly and mild hypertelorism at 24 months of age. However, no distinct facial dysmorphism was observed. The result of mitochondrial genome sequencing regarding generalized hypotonia and epilepsy was confirmed as normal.
At 36 months of age, WES was conducted. The results found a de novo genetic variant in the BRAF gene.
Both boys' final diagnosis was 'Cardio-facio-cutaneous syndrome.' To learn details about the disease, visit Rare Disease Series #13: Cardio-facio-cutaneous syndrome.
What we have to keep in mind
In conclusion, both boys presented different symptoms at different time periods, even though they had a genetic variant on the same gene.
Like the second boy's story, doctors usually perform tests related to the diseases they are familiar with. However, since there can be various genetic causes for one phenotype, it is best to perform genetic tests that cover all genes using WES or WGS(Whole genome sequencing).
Cardio-facio-cutaneous syndrome (MIM# 115150)