2. Introduction
• Cornelia de Lange Syndrome (CdLS) is a GENETIC
DISORDER!
• It is a syndrome of multiple congenital anomalies
characterized by a distinctive facial appearance, prenatal
and postnatal growth deficiency, feeding difficulties,
psychomotor delay, behavioral problems, and associated
malformations that mainly involve the upper
extremities.
• The syndrome is named after Dutch pediatrician
Cornelia Catharina de Lange, who described it in 1933.
• It is often termed Brachmann de Lange syndrome or
Bushy syndrome and is also known as Amsterdam
dwarfism.
3. Epidemiology
Frequency
• The incidence is 1 case per 10,000-50,000 live births. No
differences based on sex or race have been described.
Mortality/Morbidity
• Gastrointestinal disease complications are one of the most
common causes of death in this syndrome. They include
diaphragmatic hernia in infancy and aspiration pneumonia
and volvulus at an older age.
• A retrospective review of 295 propositi with Cornelia de Lange
syndrome found that respiratory issues (eg, aspiration, reflux,
pneumonia) were the most common causes of death (31%),
followed by gastrointestinal disease, including
obstruction/volvulus (19%), congenital anomalies (15%).
4. Genetics
• NIPBL (5p13) accounts for the majority of CdLS cases
• SMC1A (Xp11) accounts for less than 5%
• SMC3 (10q25) is involved in rare cases
• All genes involved code for components of the cohesin
complex. Cohesin secures sister chromatids during cell
division
• NIPBL is particularly expressed in the upper extremities
and face, and mutation is associated w/ the classic CdLS
phenotype; SMC1A and SMC3 mutations are associated
w/ less severe CdLS phenotypes
• Due to sporadic mutations in almost all cases :
autosomal dominant
5. Clinical Features
General
• Microcephaly
• Short stature
• Feeding problems
• Cutis marmorta
Craniofacial
• Short neck
• Low posterior hairline
• Hypertrichosis
• Arched eyebrows,
synophrys
• Low set ears
• Long philthrum, thin
upper lip w/ downturned corners
• Cleft palate
• Widely spaced teeth
• Micrognathia
6. Extremities
• UEX malformations
• Small hands, feet
• Clinodactyly
• Disproportionately short thumbs, proximally placed
GI
• GERD
• Pyloric stenosis
• Congenital diaphragmatic hernia
Urogenital
• VUR
• Renal dysplasia
• Micropenis/ small labia majora
• Hypospadias
11. Diagnosis
• Presumptive diagnosis can be made clinically,
based on the history and physical exam,
particularly the facial appearance
• Genetic testing can confirm the diagnosis (80%
cases are positive)
• Prenatally – ultrasound at 18 weeks
12. Imaging Studies
• Radiography may reveal the following:
• Delayed bone age (100%)
• Long-bone abnormalities,
• Hiatal hernia
• Aspiration pneumonia (50%)
• Gastroesophageal reflux (90%)
• Intestinal obstruction, malrotation, volvulus (17%)
• Ultrasonography at diagnosis to assess for kidney and
urinary tract abnormalities
• Echocardiography is indicated for evaluation of
congenital heart disease.
• Radiologic brain findings may include enlarged
ventricles, including thinning or atrophy of white matter,
particularly frontal lobes, with relative sparing of
parietal lobes; brainstem hypoplasia; and cerebellar
vermian hypoplasia or agenesis.
• Other tests - Hearing evaluation is recommended
13. Scoring System for Severity of CdLS
Parameter 1 point 2 point 3 point
Birth weight Above 2,500 g 2,000–2,500 g Below 2,000 g
Sitting alone < 9 mo 9–20 mo >20 mo
Walking alone < 18 mo 18–42 months >42 mo
Saying first
word
< 24 mo 24–48 mo >48 mo
Upper limb
malformation
No defect
Partial defect (<2
digits)
Severe defect (> 2
digits)
Number of
other major
malformations
0-1 2-3 >3
Hearing loss Absent ... ...
A score of less than 15 points indicates mild involvement, a score of 15-22
points indicates moderate involvement, and a score of more than 22
points indicates severe involvement.
14. Management
• Often, an interdisciplinary approach is recommended to treat
the issues associated with CdLS. A team for promoting the
child's well-being often includes speech, occupational and
physical therapists, teachers, physicians, and parents.
• Ongoing physical, occupational, and speech therapies
• Surgery to treat skeletal abnormalities, gastrointestinal
problems, congenital heart defects and other health problems
• Medications to prevent or control seizures.
• Research into CdLS ongoing
