Evaluating at-risk
relatives. FISH,
qPCR, or other quantitative methods of targeted duplication analysis can be used to identify the
7q11.23 duplication in at-risk relatives of the proband.
Testing parental samples is important in determiningrecurrence
risk
Clinical
Characteristics
Clinical Description
Infancy. Median birth weight is at the 75th centile, median birth length is at the
80th centile, and
median head circumference is at the 75th centile (30% of newborns have an OFC
≥95th centile).
Infants with the 7q11.23 duplicationsyndrome
are hypotonic and may have joint laxity, resulting in delayed attainment of
motor milestones. Median age of walking is 1.33 years
Approximately 30% of
individuals with the 7q11.23 duplication syndrome have one or more congenital anomalies. Congenital malformations
that have been reported in more than one individual include cleft lip and/or
palate, congenital heart disease, diaphragmatic hernia, unilateral renal
agenesis, vertebral anomalies, cryptorchidism, and talipes equinovarus;
however, no consistent specific pattern of malformations has been observed
[Speech is significantly delayed with median age of single words at 2.00 years
based on parental report. Among probands who eventually are diagnosed with the
7q11.23 duplication syndrome, the most common reason for
evaluation was developmental delay; the second most common reason was autism
spectrum disorder (ASD) [Neurologic problems. Neurologic examination of children
with the 7q11.23 duplication syndrome is abnormal in 89%; findings
include hypotonia (60%), abnormalities in gait and station such as wide-based
gait and difficulty with balance (62%), and adventitious movements such as
involuntary motor overflow (83% of children age >14 years). Developmental
coordination disorder is present in 74% [Morris et al 2015].
Seizures are present in
19% [Hydrocephalus requiring shunting was present in 5.6% in one series When
asked to indicate behavioral concerns regarding their child, 25% of parents
reported that he/she exhibited high pain tolerance [Morris et al 2015].
Neuroimaging. Common MRI findings include varying degrees of
ventriculomegaly, thin corpus callosum, increased extra-axial spaces, thin
white matter, delayed myelination, posterior fossa cysts, and cerebellar vermis
hypoplasia [.
Craniofacial features. The characteristic craniofacial phenotype including macrocephaly, brachycephaly,
broad forehead, straight eyebrows, deep-set eyes, long eyelashes, broad nasal
tip, low insertion of the columella, short philtrum, thin vermilion of the
upper lip, high-arched palate, and minor ear anomalies (overfolded helix,
protruding ears) is observed at all ages (Figure 1). Facial asymmetry
and low-hanging columella become more evident/are more common in older children
and adults (Figure 2).
Cardiovascular disease. Patent ductus arteriosus is present in 15%-21 and
septal defects are present in 2%.
Aortic dilation may be
detected at any age; surgical correction has been required in some adolescents
and adults. Some individuals with dilation of the ascending aorta also have had
dilation of the aortic roott . The prevalence of aortic dilation is 46%
Cognitive abilities. Median IQ is 85 (low average), with a range from
severe intellectual disability to superior ability. On average, verbal,
nonverbal reasoning, and spatial abilities are at about the same level,
although a variety of patterns of relative strengths and weaknesses occur.
Median reading achievement performance is at the bottom of the average range
(varying from severe disability to superior) and median mathematics achievement
performance is at the bottom of the low average range (also varying from severe
disability to superior)
More about 7q11.23 duplication syndrome::--- Expand your knowledge on
this subset of newborn with FISH &PCR technology: Speech and language
difficulties. Severe delay in
expressive language was the presenting feature in the first individual reported
with the 7q11.23 duplication syndrome DSM-5 speech sound disorder,
present in 82%, includes articulation disorders (motor speech disorders such as
childhood apraxia of speech) and phonologic disorders (cognitive-linguistic
disorders reflecting inaccurate or incomplete phonologic representations or
inappropriate phonologic rules).
The most common speech
sound disorder in children with 7q11.23 duplication is childhood apraxia of speech (a
neurologic speech disorder not due to muscle weakness or muscle tone
differences but rather due to problems of planning and coordinating the muscle
movements needed to pronounce words) or manifestations of this disorder.
The most common disorders
are specific phobia (53%), social anxiety disorder (50%), selective mutism
(29%), and separation anxiety disorder (13%)
Childhood
dysarthria or its manifestations (usually resulting from low muscle tone) are
also common [ “Developmental” speech problems, such as distortions of /s/ or
/r/, may persist past typical ages.
On omnibus tests of
language abilities (including receptive and expressive modalities and
vocabulary and grammar) overall performance is most commonly in the range of
mild to moderate language disorder but can range from severe language disorder
to average language ability. For most children vocabulary abilities are
stronger than grammatic abilities.
School-age children who
had had consistent speech-language therapy from late infancy or early
toddlerhood had considerably stronger language and literacy skills than
children who had not. Children who were taught to read using a strong phonics
approach had better reading skills than children taught with sight-word or
whole-word approaches .
Adaptive behavior. Adaptive skills are more limited than expected for IQ.
Median performance is at the mild adaptive deficit to borderline level, ranging
from severe adaptive deficit to average. Executive functioning difficulties
also may be observed
Behavior problems. Anxiety disorders are common, with approximately 60%
meeting DSM criteria for at least one anxiety disorder other than specific
phobia. The most common disorders are specific phobia (53%), social anxiety
disorder (50%), selective mutism (29%), and separation anxiety disorder (13%)
Approximately 35% met DSM
criteria for ADHD and about 25% met DSM-IV criteria for oppositional defiant
disorder or disruptive behavior disorder – not otherwise specified An elevated
rate of physical aggression is also common.
The 7q11.23 duplication syndrome is associated with an
elevated risk for autism autism spectrum disorder was the second most common
indicator for genetic testing Thirty-three percent screened positive for a
possible autism spectrum disorde] and approximately 20% met criteria for an
autism spectrum disorder based on a gold-standard assessment (ADOS-2 and ADI-R plus clinical judgment) with
differential diagnosis taking into account selective mutism and social anxiety.
Eye, ear, nose, and
throat
- Strabismus is present in 15%.
- Hearing loss has been reported in ~5%.
- Diastema is present in 31%, high-arched palate in
44%, and micrognathia in 30% [Chronic otitis media affects 25% of
children; ventilating tubes are placed in 15% and tonsillectomy and
adenoidectomy are performed in 15%.
Gastrointestinal
difficulties. Infants
with the 7q11.23 duplication syndrome may have feeding problems
such as difficulty with latching on, and 7.5% have persistent feeding problems
requiring gastrostomy tube feeding. Chronic constipation is a significant
problem in 66% of children and 27% of adults. Encopresis occurs in 20% of the
children with constipation and 7.5% require hospitalization for disimpaction
Genitourinary tract
abnormalities. Congenital
anomalies of the urinary tract occur in 15%-18%, including hydronephrosis and
unilateral renal agenesis Females with unilateral renal agenesis may have
abnormalities of müllerian structuresApproximately 15% of males have
cryptorchidism Musculoskeletal problems. Joint laxity may be present in young
children. Talipes equinovarus (5%) responds to casting [
Endocrine problems. Most affected individuals have normal stature.
Growth hormone deficiency is found in 9% [
Other. Cutis marmorata is present in 45% of children younger
than age 14 years
Genotype/Phenotype Correlations
In classic Williams
syndrome, the 7q11.23 deletion comprises 1.55 megabases (Mb) in 95%
and 1.84 Mb in 5% [. Duplications of both sizes have been reported but the
proportion of individuals with each of the two sizes has not been determined.
Longer duplications
including HIP1 have been reported [ noted that these individuals did not
seem to differ phenotypically from individuals with the recurrent 7q11.23 duplication.
However, systematic comparisons to a large group of individuals with the
recurrent 7q11.23 duplication are needed to determine if longer duplications
are associated with a more severe phenotype,
considering that longer deletions of 7q11.23 including HIP1 are associated with more severe
intellectual disability than is typical for individuals with classic deletions
[Stock et al 2003].
Shorter 7q11.23
duplications have also been reported [Zarate et al 2014, Parrott et al 2015].
Systematic comparisons to a large group of individuals with the recurrent
7q11.23 duplication are needed to determine phenotypic
similarities and differences as a function of the specific genes duplicated.
Given
the small number of individuals identified with a 7q11.23 triplication and the
variable size of the triplication, it is not yet known if the phenotype associated with the triplication is
more severe than that 
No comments:
Post a Comment