Fetal anomalies
Gene: BICD2
PMID 27751653: describe two isolated probands presenting in utero with features associated with reduced fetal movements. Both cases diagnosed at birth with arthrogryposis multiplex congenita (AMC) and hypotonia. A recurrent de novo missense mutation was identified in both cases.
PMID 29274205 describe a fetal case in which phenotype included legs fixed in extended position, arms fixed flexed over the face, and absent fetal movements and hydrops fetalis. A de novo missense variant in BICD2 was identified.
PMID 28635954 describes a spectrum of BICD2-opathies, including individuals with reduced fetal movement.
P2-62 (abstract) ISPD 2018 identified a VUS in BICD2 in a fetus with severe arthrogryposis.
P2–137-LB (abstract) ISPD 2018 identified de novo BICD2 mutation in fetus with fetal hydrops, multiple contractures and pterygium.Created: 12 Nov 2019, 11:07 a.m. | Last Modified: 12 Nov 2019, 11:07 a.m.
Panel Version: 0.346
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
HP:0002804; HP:0001059
Publications
Comment on list classification: Updated rating from Red to Green based on external review highlighting literature evidence of fetal phenotypes, and agreement from Lyn Chitty and Rhiannon Mellis (Great Ormond Street Hospital).Created: 2 Dec 2019, 10:46 a.m. | Last Modified: 2 Dec 2019, 10:46 a.m.
Panel Version: 0.371
PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic women with subclinical findings with the previously described p.(Thr703Met) variant.Created: 29 Nov 2019, 1:49 p.m. | Last Modified: 29 Nov 2019, 1:49 p.m.
Panel Version: 0.367
PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant.Created: 29 Nov 2019, 1:48 p.m. | Last Modified: 29 Nov 2019, 1:48 p.m.
Panel Version: 0.367
PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth. The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands.Created: 29 Nov 2019, 1:48 p.m. | Last Modified: 29 Nov 2019, 1:48 p.m.
Panel Version: 0.367
OMIM Clinical Synopsis for MIM:618291 now mentions onset in Utero, including fractures in utero and decreased fetal movements, as noted by Rhiannon Mellis.Created: 29 Nov 2019, 1:05 p.m. | Last Modified: 29 Nov 2019, 1:05 p.m.
Panel Version: 0.367
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted BICD2 gene rating from Green to Red.Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCECreated: 11 Dec 2018, 9:04 a.m.
In the original PAGE file, MOP listed as All missense/in frame.Created: 8 Nov 2018, 4:45 p.m.
Mode of pathogenicity
Other - please provide details in the comments
Gene: bicd2 has been classified as Green List (High Evidence).
Publications for gene: BICD2 were set to 27751653; 29274205; 28635954
Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis; Pterygium
Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis
Mode of pathogenicity for gene: BICD2 was changed from to Other
Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Publications for gene: BICD2 were set to
Source Expert Review Red was added to BICD2. Rating Changed from Green List (high evidence) to Red List (low evidence)
gene: BICD2 was added gene: BICD2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: BICD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: BICD2 were set to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE