Cornelia de Lange Syndrome (CdLS) is a genetic disorder characterized by distinctive facial features, growth deficiencies, and malformations of the limbs and organs. It is caused by mutations in structural components of the cohesin complex and has an incidence of 1 in 10,000-50,000 live births. Clinical features include microcephaly, short stature, intellectual disability, and gastrointestinal issues. Diagnosis is made clinically or through genetic testing, and management requires a multidisciplinary approach including various therapies and treatments for associated health problems.

1. Cornelia de Lange Syndrome
Justly Ann Thomas
Group 4

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

7. Neurological
• Seizures
• Sleep disturbances
• Myopia
• Hearing loss
Neurobehavioral
• Intellectual disability
• Self injurious behaviour
• ADHD
• Autistic features

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