Cornelia De Lange Syndrome Workup

Updated: Jul 21, 2023
  • Author: Dayna Morel Swols, MSc; Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

Molecular genetic diagnosis can be performed using sequencing and deletion/duplication analysis of NIPBL, SMC3, RAD21, SMC1A, and HDAC8.

This testing can confirm the diagnosis, especially in mild or atypical cases, and the results can help in identifying the family specific mutation for prenatal testing in future pregnancies. Updated laboratory information can be obtained at Gene Tests.

CBC analysis has led to a finding of thrombocytopenia.


Imaging Studies

See the list below:

  • Radiography may reveal the following:

    • Delayed bone age (100%)

    • Spurs in the anterior angle of the mandible (42%) and a prominent symphysis (66%)

    • Digital abnormalities, which range from acheiria to oligodactyly

    • Long-bone abnormalities, including ulnar aplasia and/or hypoplasia, aplasia and/or hypoplasia of the radial head, or fusion of the elbow: When a single forearm bone is present, fusion at the elbow and oligodactyly often occur; this condition makes it difficult to determine if the radius or ulna is absent.

    • Hypoplastic first metacarpal (79%), hypoplastic fifth middle phalanx (93%), and clinodactyly (64%)

    • Short sternum with precocious fusion (54%)

    • Thirteen ribs (56%)

    • Thin rib cortices with undulating appearance (33%)

    • Hiatal hernia

    • Aspiration pneumonia (50%)

    • Gastroesophageal reflux (90%)

    • Intestinal obstruction, malrotation, volvulus (17%)

    • Pelvic abnormalities (33%)

  • Ultrasonography at diagnosis to assess for kidney and urinary tract abnormalities (40%) may reveal the following:

    • Horseshoe kidney

    • Altered corticomedullary differentiation

    • Pelvic dilation

    • Small kidneys

    • Renal cysts

    • Renal ectopia

  • Voiding cystourethrography is indicated for evaluation of recurrent urinary tract infections or hydronephrosis.

  • Echocardiography is indicated for evaluation of congenital heart disease.

  • Radiologic brain findings may include enlarged ventricles, including enlargement of basal cisterns; 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 in Cornelia de Lange syndrome.

High-resolution chromosomal studies are indicated when the syndrome's diagnosis is uncertain.

A spectrum of endocrinopathies may be observed in this disorder in addition to growth-hormone deficiency. These conditions include problems relating to gonadotropin and prolactin secretion and panhypopituitarism. In a study of 24 patients with Cornelia de Lange syndrome, Ascaso et al found hyperprolactinemia to be the most common endocrine disorder. Mildly delayed puberty and genital abnormalities, such as cryptorchidism, were noted in the cohort, and the presence of subclinical hypothyroidism was reported in three individuals. In three prepubertal patients, lab results suggested insulin resistance, despite a lack of risk factors. The group demonstrated, on average, normal levels of insulin-like growth factor 1 and insulin-like growth factor–binding protein 3. [23]



Diagnosis requires (1) positive mutation finding on Cornelia de Lange syndrome gene testing; (2) confirmed facial findings and confirmed criteria from any 2 of the growth, developmental, or behavioral categories; or (3) confirmed facial findings and confirmed criteria for 3 other categories, including one from growth, developmental, or behavioral categories and 2 from the other categories. [24]

  • Facial characteristics must include synophrys and at least 3 of the following:

    • Long eyelashes

    • Short nose, anteverted nares

    • Long, prominent philtrum

    • Broad or depressed nasal bridge

    • Small or square chin

    • Thin lips, down-turned corners

    • High palate

    • Widely spaced or absent teeth

  • Growth characteristics must include at least 2 of the following:

    • Weight below the fifth percentile for age

    • Height or length below the fifth percentile for age

    • Occipitofrontal circumference below the second percentile for age

  • Developmental characteristics must include at least 1 of the following:

    • Developmental delays or mental retardation

    • Learning disabilities

  • Behavioral characteristics must include at least 2 of the following:

  • Musculoskeletal characteristics include reduction defects with absent forearms alone, small hands or feet (below the third percentile for age) or oligodactyly and at least two of the following, or none of these features and at least three of the following:

    • Clinodactyly of the fifth finger

    • Abnormal palmar crease

    • Radial head dislocation, abnormal elbow extension

    • Short first metacarpal, proximally placed thumb

    • Bunion

    • Partial syndactyly toes

    • Scoliosis

    • Pectus excavatum

    • Hip dislocation or dysplasia

  • Neurosensory and skin characteristics must include at least 3 of the following:

    • Ptosis

    • Tear duct malformation or blepharitis

    • Myopia

    • Major eye malformation or peripapillary pigmentation

    • Deafness or hearing loss

    • Seizures

    • Cutis marmorata

    • Hirsutism, generalized

    • Small nipples and/or umbilicus

  • Other major system characteristics must include at least 3 of following:

    • GI malformation/malrotation

    • Diaphragmatic hernia

    • Gastroesophageal reflux disease

    • Cleft palate or submucous cleft palate

    • Congenital heart defect

    • Micropenis

    • Hypospadias

    • Cryptorchidism

    • Renal or urinary tract malformation

Table. Scoring System for Severity of Cornelia de Lange Syndrome [24] (Open Table in a new window)


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




Hearing loss




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.