Cornelia de Lange syndrome

Classic

Cornelia de Lange syndrome with variant of unknown significance detected in NIPBL gene mutation: a case report. Clinical findings of the patient

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Cornelia de Lange syndrome (CdLS) is an extremely rare clinically heterogeneous developmental disorder of unknown etiology. Although the described clinical symptomatology is very broad, the majority of cases include growth impairment, learning disability and dysmorphic facies.

Epidemiology

The estimated incidence is at ~1:10,000-30,000 births . There is no recognized racial or gender predilection .

Clinical presentation

The syndrome carries a wide spectrum of clinical features which include:

facial dysmorphism
- low set hairline in the front and back
- long eyelashes
- bushy eyebrows
- synophrys (unibrow)
- upturned nose with anteverted nostrils
- thin lips with long philtrum
- micrognathia
- microbrachycephaly, microcephaly or brachycephaly
upper limb malformations
- short 1^st metacarpal
- oligodactyly
- acheiria
- micromelia
growth restriction including intrauterine growth restriction
intellectual disability
hirsutism
hearing impairment
intestinal malrotation
congenital diaphragmatic herniation
congenital cardiac anomalies
genitourinary anomalies
- hypospadias
- cryptorchidism

Pathology

Genetics

Most cases are thought to be sporadic resulting in a new autosomal dominant mutation . Occasional autosomal dominant and autosomal recessive forms are known. Some have abnormalities in chromosome 3q26.3. Heterozygous mutations in the cohesin regulator, NIPBL, or the cohesin structural components SMC1A and SMC3, have been identified in approximately 65% of individuals with Cornelia de Lange syndrome . Other implicated genes are RAD21 and HDAC8 .

Markers

low PAPP-a
abnormally low maternal serum alpha fetoprotein (MSAFP) levels have been described in some cases

Radiographic features

Antenatal ultrasound

May demonstrate many of the above clinical features. An early - first trimester - ultrasound scan may show an increased nuchal translucency as a non-specific but early sign .