CORNELIA DE LANGE SYNDROME
DEFINITION:
A disorder of unknown etiology resulting in a syndrome
characterized by specific dysmorphic features.
EPIDEMIOLOGY:
- incidence: 1/30,000-60,000 live births
- age of onset:
- newborn (dysmorphic features)
- risk factors:
- familial - ? autosomal recessive
- M = F
- no geographic predisposition (worldwide)
HISTORY:
- young physician in training
- interrupted study of case to report for active duty - WW1
- patient:
- 1st child, SVD @ 1600g @ term
- admitted to hospital on day 6 - weak and vomiting
- finally refused all nourishment and died at 16 days of
pneumonia
- dysmorphic features:
- microcephaly, brachycephaly, sloped forehead,
micrognathia, beaked nose, well-formed ears - small arms
with hypoplastic forearms, flexed at elbows, antecubital
web, symmetrical monodactyly with 2 phalanges
- dwarfism, cervical ribs, hirsutism
- report found by Dr. Opitz (U. of Wisconsin) in 1963
- Opitz (1965) recommended "Brachmann-de Lange Syndrome BDLS"
2. 1933 - Cornelia de Lange (1971-1950)
- Professor of Peds at U. of Amsterdam
- reported on two unrelated children with the syndrome
- in 1938 reported a third patient and post-mortem findings on
the first patients
- in 1941 presented account of patients at the Neurological
- Society of Amsterdam
3. Post 1933
- 1933-42 - 5 cases reported
- 1943-52 - 6 more cases reported
- 1953-62 - 16 more cases reported
- 1963-68 - 209 more cases; Total= 236
CLINICAL FEATURES:
- microcephaly +/- brachycephaly
- micrognathia
- low hairline
- low set ears
- dilated veins on temples +/- forehead
- synophris (confluent eyebrows)
- long curly eyelashes
- broad and/or depressed nasal bridge
- anteverted nostrils
- prominent philtrum
- thin upper lip
- downturned angles of mouth
- high arched palate
- delayed eruption of teeth
- bluish tinge around eyes, nose +/- mouth
2. Extremities
- limitation of extension at elbows
- small hands and feet with short digits
- single transverse palmar crease
- clinodactyly of fifth fingers
- proximally placed thumbs
- webbing of 2nd and 3rd toes
3. Others
- mental retardation
- growth retardation
- hirsutism
- cutis marmorata
- birth weight <2500g
- neonatal difficulty with feeding +/- respiration
- also see Preus and Rex, (1983)
2. Organ Malformations
- cortical atrophy with lack of myelination
2. Respiratory
- abnormal lobation or parital agenesis
3. Cardiovascular
- ASD, VSD, PDA
- rudimentary left ventricle
- anomalous systemic venous drainage
- overriding aorta
- ventricular fibro-elastosis
4. Gastrointestinal
- malrotation or incomplete fixation
- duplication
- splenic-pancreatic fusion
5. Genitourinary
- polycystic and ectopic kidneys
- duplication of ureter
- bicornuate uterus
- ovarian and testicular hypoplasia
6. Endocrine
- hypoplasia of adrenals, thyroid
7. Ocular
- unusual palpebral fissures - narrow, anti-mongol, mongol
- strabismus
- ptosis
- nystagmus
- epicanthal folds
- others: eccentric pupils, microphthalmia, optic atrophy,
corneal opacities, lacrimal duct stenosis, exo-phthalmos,
photophobia, cataracts, colobomata, heterochromia, blue
sclerae
3. Behavioural Phenotypes
- avoid/reject social interactions with strangers or family
- avoid physical contact
- infrequently exhibit facial expressions of emotion
- frequently display stereotypic movements
- self-stimulatory
- self-mutilative
- vestibular stimulation or vigorous movement elicits
pleasurable responses
- no speech - low pitched, growling monotonous sounds
INVESTIGATIONS:
- skull - small, brachycephalic, small mandible
- limbs - delayed osseous maturation
- short thick or absent metacarpals & phalanges
- short 1st metacarpal -> proximally placed thumb
- hypoplasic middle phalanx of 5th finger -> 5th finger
clinodactyly
- shortening of long bones, metatarsals, phalanges
- chest - minor changes in ribs
2. Barium
- if suspect congential intestinal malformations with per-sistent
vomiting
3. CT/MRI
- cortical atrophy and lack of myelination
2. EEG
- both normal and abnormal findings
- i.e., generalized subcortical hyperexcitability, myotonic
episodes, hypsarrhythmia, focal epilepsy
3. Serum
- normocytic normochromic anemia
- leukocytosis with normal differential
- normal biochemistry
4. Endocrine
- short stature with normal growth hormone
- adrenocortical insufficiency due to hypopituitarism
- hypothryoidism
- ? reproduction
5. Karyotype
6. Normal
MANAGEMENT:
- behavioural modification programmes
- prostheses for malformed limbs
- corrective surgery for malformations
- genetic counselling
- recurrence risk, prognosis
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