[source]
pmid = PMID:29127725
title = A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
[diagnosis]
disease_id = OMIM:174300
disease_label = Orofaciodigital syndrome V
[text]
Patient 1  was the first born from healthy parents, non-consanguineous for their account.
Family history was unremarkable, except for three prior spontaneous
miscarriages. The pregnancy was complicated by intrauterine growth
retardation. Delivery at term was normal, with a weight at birth of
2,350 g (<3rd centile), length of 47 cm (3rd centile), and occipital–
frontal circumference of 32 cm (5th centile). APGAR scores were 6 and
9 at 1 and 5 min, respectively. He had bilateral postaxial extra-digits
on his hands that were surgically removed in his late childhood. He
also had bilateral cutaneous syndactyly of fingers 2–5, clinodactyly of
the fifth fingers, and fingertip pads. His lower limbs were normal. Since
the first months of life, he developed generalized seizures, which were
controlled by anticonvulsant drugs. Developmental milestones were
delayed and the patient showed cognitive difficulties during childhood,
with an I.Q. of 70 (Terman-Merril scale) measured at the age
of 9 years. For these reasons, he has undergone developmental and
speech therapies since the age of 3 years. At the age of 17 years, his
height was 165 cm (3rd centile), weight was 67 kg (50th centile), and
head circumference 53 cm (10th centile). He had distinctive facial features,
including prominent thick eyebrows, malocclusion, high-arched
palate, and rounded prominent jaw (Figure 1G and H).
A cerebral magnetic resonance imaging (MRI) disclosed thinning of the cerebral cortex
in front of the ventricular collateral trigone (not shown).
Wakefulness electroencephalograms showed diffuse high amplitude slow
waves intermingled with sharp waves or spikes. Since early adulthood
he started to complain of migraine. As part of his neurological presentation,
he also presented lower limbs weakness and some walking difficulties. At the age of 30, after an episode of loss of consciousness
associated with generalized seizures, he underwent a follow-up brain
MRI scan, which showed diffuse white matter signal abnormalities and
multifocal cortical–subcortical infarcts involving both cerebral hemispheres (Figure 1P and Q).
