Limb disorders

Gene: FZD2

I don't know

Robinow syndrome White AJHG 2018

Created: 1 Aug 2019, 5:10 p.m. | Last Modified: 1 Aug 2019, 5:10 p.m.

Panel Version: 1.24

I don't know

Comment on list classification: 4 families, three with brachydactyly and variable presence of other features (clinodactyly, camptodactyly, broad 1st digits). Genomics England clinical team confirm it is appropriate for the limb disorders panel as well as the skeletal dysplasia panel.

Created: 26 Nov 2019, 12:02 a.m. | Last Modified: 26 Nov 2019, 12:02 a.m.

Panel Version: 1.118

Associated with Omodysplasia 2 (#164745) in OMIM.

Omodysplasia 2:

PMID: 25759469 - Saal et al. 2015 - 1 case - a mother and daughter with omodysplasia were found to have a FZD2 mutation (c.1644G>A, p.Trp548*). The variant was found to have occurred de novo in the mother. The altered protein is still produced in vitro, but is shown to have reduced ability to interact with its downstream target DISHEVELLED. The mother had multiple anomalies, including bilateral cleft lip and cleft palate, short upper extremities, dysmorphic facial features and hypoplastic labia and clitoris. Skeletal X rays of the daughter showed hypoplasia of T11 vertebral body and bilateral dislocation of the radius with short humeri. At 6 years musculoskeletal examination showed primarily rhizomelic shortening of the upper extremities and a mild shortening of the forearms with limited forearm supination/pronation. There was mild fifth finger clinodactyly with no brachydactyly.

Robinow syndrome:

PMID: 29276006 - White et al 2018 - 4 families with at least one individual clinical diagnosed with Robinow or Robinow-like phenotypes and with variants in FZD2 were identified . All showed limb phenotypes including mesomelic limb shortening (3 families, mild in one case), brachdactyly (3 families), proximaly implanted thumbs (1 family), Medelung deformity (1 family).

Created: 6 Aug 2019, 4:01 p.m. | Last Modified: 6 Aug 2019, 4:01 p.m.

Panel Version: 1.30

Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list

Created: 1 Aug 2019, 2:08 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown