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Autosomal dominant Larsen syndrome

Orpha number ORPHA503
Synonym(s) -
Prevalence 1-9 / 1 000 000
Inheritance
  • Autosomal dominant
Age of onset Neonatal/infancy
ICD-10
  • Q68.8
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT -

Summary

Larsen syndrome (LS) is a rare skeletal dysplasia characterized by congenital dislocation of large joints, foot deformities, cervical spine dysplasia, scoliosis, spatula-shaped distal phalanges and distinctive craniofacial abnormalities, including cleft palate.

The birth prevalence of Larsen syndrome in Europe is 1/250,000 live births.

Primary clinical characteristics of LS are congenital dislocations of hip, knee and elbow joints with equinovarus or equinovalgus foot deformities (club feet). Other frequent manifestations include spinal deformities such as scoliosis and cervical spine kyphosis, sometimes associated with cervical myelopathy and short, broad, spatula-shaped distal phalanges with the thumb almost always affected. Recurrent craniofacial abnormalities include a prominent forehead, depressed nasal bridge, flattened midface and ocular hypertelorism. Midline cleft palate and conductive hearing loss have also commonly been reported.

LS is due to missense mutations or small in-frame deletions in the FLNB gene (localized to 3p14.3) that encodes cytoskeletal protein filamin B.

Diagnosis is established by clinical assessment, and skeletal X-rays displaying, amongst other factors, supernumerary carpal and tarsal bone ossification centers and is confirmed by genetic testing.

Differential diagnosis includes other more severe and lethal FLNB-related disorders: atelosteogenesis type I, atelosteogenesis type III and boomerang dysplasia as well as otopalatodigital syndrome type I and spondyloepiphyseal dysplasia, CHST3 type; chondrodysplasia with joint dislocations, gPAPP type; Larsen-like syndrome, B3GAT3 type; Reunion island's Larsen syndrome and Desbuquois syndrome (see these terms).

Prenatal diagnosis is available for those with a family history of LS.

LS is transmitted in an autosomal dominant manner. The autosomal recessive cases reported in the past may perhaps correspond to parental germline mosaicism, but are more likely to represent more recently defined recessive syndromes with similar presentations.

Management should be adapted to each patient and may involve orthopedic treatment and monitoring, surgical procedures, especially for hip dislocation, and physiotherapy. In case of hearing loss, a multidisciplinary team with pediatric expertise is recommended. It is essential that all infants with a clinical diagnosis of LS have their cervical spine evaluated as soon as practicable after birth to exclude life-threatening cervical spine instability.

LS does not affect life-expectancy.

Expert reviewer(s)

  • Pr Stephen ROBERTSON

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Detailed information

Clinical genetics review
  • EN (2013)
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