Inspired by a patient
Is there a 5q14.3 deletion syndrome?
At the moment, very few people have been reported with a
molecular diagnosis of a
5q14.3 deletion. However, the reports that exist show
remarkable similarities. These
similarities are listed below and constitute an emerging
syndrome.
Most likely features
Early and severe
hypotonia [low muscle tone]
Marked developmental
delay
Epilepsy
Marked learning
disability and need for special support
Marked delay in
learning to sit and move
Marked language
delay. Most children do not speak but communicate in other ways
Delay in making eye
contact
Stereotypic or
unusual movements
Some unusual facial
features
Brain abnormalities
on magnetic resonance imaging [MRI]…
Epilepsy
Most babies and children with a 5q14.3 deletion have
seizures but in many the seizures
improve and in some they stop altogether. Out of 20 children
with a 5q14.3 deletion
that includes the entire MEF2C gene, all bar one
18-month-old child have had seizures
and he was found to have an abnormal EEG
[electroencephalogram recording of the
wave patterns from the continuous tiny electrical signals
coming from the brain].
In most children, seizures start in the first year, often
before six months; in one baby
they started on the first day of life and in another at 16
months. One child has only had
febrile seizures [see page 6], has not been diagnosed with
epilepsy and at the age of 4 is
not taking anti-epileptic drugs [AEDs]. Another 13-month-old
girl with a history of an
abnormal EEG and seizure-like episodes which appear as an
involuntary upward eye
gaze is being investigated for the possibility that these
are not in fact seizures.
Among three children with a partial deletion of the MEF2C
gene, two have seizures,
while a three-year-old boy has no seizures and a normal EEG.
Among nine children
with a 5q14.3 deletion, the oldest 15, but where the MEF2C
gene is preserved intact,
five have not had seizures. Among the four who have
seizures, they started later in one
child – at 4 years 9 months – than is typical in children
who have lost the MEF2C gene…
Absent or severely delayed speech
While a typically-developing baby usually coos and babbles
by six months, produces
speech-like noises in the next months and says
understandable words around their first
birthday, speech and language development in a baby with a
5q14.3 deletion is different.
Overall, progress is slower but one Unique baby was cooing
at eight months; another
knew to ask or say baba when she was hungry at 14 months;
others are making a range
of vowel and consonant sounds or babbling [mama, baba, dada]
by seven months to
three years. One child is saying single words [no, bottle,
mama, Elmo, yeah] by 20
months but others only use words years later, if at all.
Children with a 5q14.3 deletion draw on a rich variety of
alternatives to speech and
language. They may use subtle facial expressions, smile,
cry, laugh or look sad, they may
use modified signs, body language, pushing things away or
pulling them close. They may
shout or make vocal noises. They may mimic sounds but not in
a meaningful context.
As they mature, some children use alternative communication
aids such as picture
exchange systems or electronic speaking aids.
Once reasonably consistent eye contact has been established,
babies can let you know
when they have understood you – and by and large they
understand better than they
can speak. A baby who can hold his gaze can watch your mouth
as you talk. All the
same, children need time to process even one-word
instructions like ‘No’ and their low
muscle tone means that they have difficulty complying. One
22-month-old baby can,
with time, show that he understands he should lift his legs
up [nappy change]; arms up
[dressing]; or open his mouth for medicine - but he cannot
yet carry out the actions.
Children qualify for speech and language therapy but
typically start in their second or
third year and all families find it helpful.
http://www.rarechromo.org/information/Chromosome%20%205/5q14.3%20deletions%20FTNW.pdf
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Park SM, Kim JM, Kim GW, Kim HS, Kim BS, Kim MB, Ko HC. 5q14.3 Microdeletions:
A Contiguous Gene Syndrome with Capillary Malformation-Arteriovenous Malformation
Syndrome and Neurologic Findings. Pediatr Dermatol. 2017 Mar;34(2):156-159.
Abstract
Deletions within chromosome region 5q14.3q15 have been
associated with a spectrum of disorders including
developmental delay,
hypotonia, absent speech, mild facial dysmorphism, seizures,
and brain
anomalies. Some cases of concomitant neurologic
abnormalities and cutaneous
vascular malformation associated with 5q14.3 deletion have
been reported.
Previously reported cases had similar features, including
multiple capillary
malformations, and neurologic abnormalities, including
epilepsy, hypotonia, and
developmental delay. We report a case of 5q14.3
neurocutaneous syndrome
presenting with multiple capillary malformations, neurologic
abnormalities, and
microdeletion in chromosome 5q14.3.
__________________________________________________________________________
Ilari R, Agosta G, Bacino C. 5q14.3 deletion neurocutaneous
syndrome: Contiguous gene syndrome caused by simultaneous deletion of
RASA1 and MEF2C: A progressive disease. Am J Med Genet A. 2016 Mar;170(3):688-93.
Abstract
We report the case of a young girl who was presented with
complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and
MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin
disorder and vascular malformations involving central nervous system is
consistent with a RASopathy. The child's neurological manifestations are
observed in most patients suffering from 5q14.3 by deletion or mutation of the
MEF2C gene. A review of the literature allowed us to conclude that the contiguous
deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a
Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the
penetrance of RASA1 and clinical manifestations of MEF2C according to the type
of deletion. This child described presents the complete symptomatology of both
deleted genes. We would also like to highlight the progression of the disorder.
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