Send to

Choose Destination
Am J Med Genet A. 2014 Jun;164A(6):1571-5. doi: 10.1002/ajmg.a.36484. Epub 2014 Mar 25.

A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency.

Author information

Genetics Service, Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, and Eastern Biology and Pathology Centre, Bron Cedex, France.


A girl patient born to healthy nonconsanguineous parents was referred at age 3 years and 2 months to our genetics department for testing due to developmental delay and postnatal microcephaly. Initial clinical evaluation revealed an overall developmental delay, mildly dysmorphic features, thin, sparse fair hair, and fair skin. Postnatal microcephaly and progressive ataxia and spasticity appeared later. Array CGH karyotyping showed a 333 kb de novo microdeletion on 3p22 covering the entire genomic sequence of a single gene, CTNNB1, which codes for β-catenin. β-catenin is a sub-unit of a multiprotein complex, which is part of the Wnt signaling pathway. In mice, a conditional homozygous β-catenin knockout displays loss of neurons, impaired craniofacial development, and hair follicle defects, which is similar to the phenotype presented by the patient described in this clinical report. Thus, CTNNB1 haploinsufficiency causes neuronal loss, craniofacial anomalies and hair follicle defects in both humans and mice. Point mutations in CTNNB1 in human have recently been reported but this is the first observation of a new recognizable multiple congenital anomaly/mental retardation syndrome caused by CTNNB1 haploinsufficiency. This clinical report should prompt a search for point mutations in CTNNB1 in patients presenting developmental delay, mild hair, skin and facial anomalies, and neurodegeneration characterized by postnatal microcephaly, and progressive ataxia and spasticity.


CTNNB1 gene; developmental delay; fair hair; haploinsufficiency; mild dysmorphic features; postnatal microcephaly; progressive ataxia; progressive spasticity; sparse

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center