5q14.3 deletion syndrome (MIM#613443) is an uncommon but well-known syndrome characterized by intellectual disability, epilepsy, hypotonia, brain malformations, and facial dysmorphism. Most patients with this syndrome have lost one copy of the MEF2C gene (MIM*600662), whose haploinsufficiency is considered to be responsible for the distinctive phenotype. To date, nearly 40 cases have been reported; the deletion size and clinical spectrum are variable, and at least 6 cases without MEF2C involvement have been documented. We herein report the clinical and cytogenomic findings of an 11-year-old girl who has a 5q14.3q21.1 de novo deletion that does not involve MEF2C but shares the clinical features described in other reported patients. Moreover, she additionally presents with bilateral cleft-lip palate (CLP), which has not been previously reported as a feature of the syndrome. The most frequent syndromic forms of CLP were ruled out in our patient mainly by clinical examination, and Sanger sequencing was performed to discard the presence of a TBX22 gene (MIM*300307) defect. Our report suggests CLP as a possible unreported feature and redefines the critical phenotypic regions of 5q14.3 deletion syndrome.

1.
Cardoso
C
,
Boys
A
,
Parrini
E
,
Mignon-Ravix
C
,
McMahon
JM
,
Khantane
S
,
Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion
.
Neurology
.
2009
;
72
:
784
92
. .
2.
Engels
H
,
Wohlleber
E
,
Zink
A
,
Hoyer
J
,
Ludwig
KU
,
Brockschmidt
FF
,
A novel microdeletion syndrome involving 5q14.3-q15: Clinical and molecular cytogenetic characterization of three patients
.
Eur J Hum Genet
.
2009
;
17
:
1592
9
. .
3.
Hotz
A
,
Hellenbroich
Y
,
Sperner
J
,
Linder-Lucht
M
,
Tacke
U
,
Walter
C
,
Microdeletion 5q14.3 and anomalies of brain development
.
Am J Med Genet A
.
2013
;
161A
:
2124
33
. .
4.
Huang
L
,
Jia
Z
,
Shi
Y
,
Du
Q
,
Shi
J
,
Wang
Z
,
Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft
.
PLoS Genet
.
2019
;
15
:
e1008357
26
. .
5.
Novara
F
,
Beri
S
,
Giorda
R
,
Ortibus
E
,
Nageshappa
S
,
Darra
F
,
Refining the phenotype associated with MEF2C haploinsufficiency
.
Clin Genet
.
2010
;
78
:
471
7
. .
6.
Ohdo
S
,
Madokoro
H
,
Hayakawa
K
.
Interstitial deletion of the long arm of chromosome 5: 46,XX,del(5)(q13q22)
.
J Med Genet
.
1982
;
19
:
479
. .
7.
Park
SM
,
Kim
JM
,
Kim
GW
,
Kim
HS
,
Kim
BS
,
Kim
MB
,
5q14.3 Microdeletions: A Contiguous Gene Syndrome with Capillary Malformation–Arteriovenous Malformation Syndrome and Neurologic Findings
.
Pediatr Dermatol.
2017
;
34
:
156
9
.
8.
Pilarowski
GO
,
Vernon
HJ
,
Applegate
CD
,
Boukas
L
,
Cho
MT
,
Gurnett
CA
,
Missense variants in the chromatin remodeler CHD1 are associated with neurodevelopmental disability
.
J Med Genet
.
2018
;
55
:
561
6
. .
9.
Shimojima
K
,
Okumura
A
,
Mori
H
,
Abe
S
,
Ikeno
M
,
Shimizu
T
,
De novo microdeletion of 5q14.3 excluding MEF2C in a patient with infantile spasms, microcephaly, and agenesis of the corpus callosum
.
Am J Med Genet A
.
2012
;
158A
:
2272
6
. .
10.
Silengo
MC
,
Luzzatti
L
,
Centerwall
WR
,
Costello
JM
,
Parslow
M
.
Interstitial deletion of the long arm of chromosome no. 5 in two unrelated children with congenital anomalies and mental retardation
.
Clin Genet
.
1981
;
19
:
174
80
. .
11.
Sobreira
N
,
Walsh
MF
,
Batista
D
,
Wang
T
.
Interstitial Deletion 5q14.3-q21 Associated With Iris Coloboma, Hearing Loss, Dental Anomaly, Moderate Intellectual Disability, and Attention Deficit and Hyperactivity Disorder
.
Am J Med Genet A
.
2009
;
149A
:
2581
3
. .
12.
Tonk
V
,
Kyhm
JH
,
Gibson
CE
,
Wilson
GN
.
Interstitial deletion 5q14.3q21.3 with MEF2C haploinsufficiency and mild phenotype: When more is less
.
Am J Med Genet A
.
2011
;
155A
:
1437
41
. .
13.
Verzi
MP
,
Agarwal
P
,
Brown
C
,
McCulley
DJ
,
Schwarz
JJ
,
Black
BL
.
The Transcription Factor MEF2C Is Required for Craniofacial Development
.
Dev Cell
.
2007
;
12
:
645
52
. .
14.
Wyatt
BH
,
Raymond
TO
,
Lansdon
LA
,
Darbro
BW
,
Murray
JC
,
Manak
JR
,
Using an aquatic model, Xenopus laevis, to uncover the role of chromodomain 1 in craniofacial disorders
.
Genesis
.
2021
;
59
(
1-2
):
e23394
18
. .
15.
Yang
YJ
,
Yao
X
,
Guo
J
,
Zhao
R
,
He
XY
,
Zhao
L
,
Interstitial deletion 5q14.3q21.3 associated with lethal epilepsy
.
Am J Med Genet A
.
2015
;
167A
:
866
71
. .
16.
Yung
JF
,
Williamson
N
,
Salafsky
I
,
Hoo
JJ
.
Deletion of band 5q21 in association with a de novo translocation involving 2p and 5q
.
J Med Genet
.
1988
;
25
:
570
2
. .
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