The child never came to our laboratory.
Only dried blood spot samples,
clinical photographs,
and a long history
of unanswered questions
did.
The child never came
to our laboratory.
Only dried blood
spot samples,
clinical photographs,
and a long history
of unanswered
questions did.
The patient had undergone multiple evaluations over the years.
Developmental delay, hypotonia and speech impairment were evident from early childhood, yet no diagnosis could fully explain the phenotype.
Several syndromes had been considered.
None of them fit.
Before the diagnosis came years of uncertainty.
These were the clinical features that repeatedly emerged throughout the patient’s history.
Developmental delay
with delayed acquisition
of motor and cognitive
milestones.
Axial and limb hypotonia
with reduced muscle tone
affecting posture and
motor development.
Pyramidal signs with
upper motor neuron
involvement affecting
the lower limbs.
Speech delay with
significant impairment
in language development
for age.
The clinical presentation was remarkably complex.
There was a reason for that.
At the time this patient was diagnosed, only 17 individuals with this syndrome had been reported worldwide. Today, GeneReviews describes approximately 75 affected individuals, illustrating how limited the available clinical knowledge was—and, to a large extent, still is.
In a situation like this, a hypothesis-driven clinical approach was unlikely to succeed.
A broader, unbiased strategy was required.
Whole genome sequencing provided that strategy.
And the diagnosis finally emerged:
Tap to reveal
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This case is based on a real clinical investigation. To protect patient confidentiality, selected identifying details have been modified or omitted without altering the educational value or the clinical message of the case.