Table 1

Summary of neuromuscular fetal akinesia genetics, 2011 and 2018

Gene symbolMIMMode of inheritanceFetal disease entity
Genes involved in motor neuron development and survival
SMN1 600354ARSMA, FADS
ERBB3 190151ARLCCS2
GLE1 603371ARLCCS1, LAAHD, non-lethal arthrogryposis
PIP5K1C 606102ARLCCS3
UBE1 314370XLXL-SMA
ERGIC1 NA AD AMC, neuropathic type
TUBB2B 612850 AD Cortical dysplasia, complex, with other brain malformations 7
Genes involved in combined central and peripheral nervous system defects
ASCC1 and TRIP4 614215, 604501 AR Congenital bone fractures 1 and 2
CNTNAP1 602346 AR LCCS7
LGI4 608303 AR AMC, neurogenic with myelin defect
Genes encoding components of the peripheral nervous system
ADCY6 600294 AR LCCS8
ADGRG6 (GPR126) 612243 AR LCCS9
ECEL1 605896 AR DA5D
GLDN 608603 AR LCCS11 (not always lethal)
PIEZO2 613629 AD, AR* MWKS, DA3, DA5, DAIPT
Genes encoding components of the neuromuscular junction
CHRNA1 100690ARLethal multiple pterygium syndrome
CHRND 100720ARAMC/CMS with fetal akinesia, FADS
CHRNG 100730ARLethal and EV MPS
CNTN1 600016ARCM with fetal akinesia
DOK7 610285ARFADS
SYNE1 608441ARAMC with fetal akinesia
RAPSN 601592ARAMC, FADS
MUSK 601296 AR CMS9, FADS
SLC18A3 600336 AR CMS21, FADS
UNC50 NA AR Lethal AMC
Genes encoding adult skeletal muscle proteins
ACTA1 102610ADFADS
BIN1 601248ARCNM with fetal akinesia
DMPK 605377ADFADS/DM
FKRP 606596ARWWS with fetal akinesia
LMNA 150330ARLGMD1B with fetal akinesia
MTM1 300415XLMTM with fetal akinesia
NEB 161650ARFADS
RYR1 180901AD, AR*FADS, CRM with fetal akinesia, MPS
TPM2 190990AD, AR*EV MPS, DA1, DA2B, NEM 4, cap myopathy 2
TNNI2 191043ADDA1, DA2B
TNNT3 600692ADDA1, DA2B
CACNA1S 114208 AD, AR Congenital myopathy, fetal akinesia
DNM2 602378 AD, AR* LCCS5
FKTN 607440 AR MDDGA4
SCN4A 603967 AD, AR* Congenital myopathy, fetal hypokinesia
VMA21 300913 XL XMEA
Genes encoding fetally expressed myostructural proteins
MYH3 160270ADDA2A, DA2B, DA8, MPS
MYH8 160741ADCC-DA7, DA7
UTRN 128240Arthrogryposis with fetal akinesia
KLHL40 615340 AR NEM8, fetal akinesia
KLHL41 607701 AR NEM9, fetal akinesia
LMOD3 616112 AR NEM10, fetal akinesia
MYOD1 159970 AR Lethal fetal akinesia
MYBPC1 160794 AD, AR* DA1B, LCCS4
TTN 188840 AD, AR* Cardiomyopathy, muscular dystrophy, fetal akinesia
ZBTB42 613915 AR LCCS6
Other genes
FGFR2 176943ADFADS
GBE1 607839ARGSD-IV/FADS
DPAGT1 191350 AR Congenital disorder of glycosylation, type Ij
  • Plain text indicates information from 2011 review. 

  • Bold text indicates new information from 2018 review. Genes with asterisks manifest severe fetal akinesia phenotypes only with recessive inheritance.

  • AD, autosomal dominant; AMC, arthrogryposis multiplex congenita; AR, autosomal recessive; CC, Carney complex; CM, congenital myopathy; CMS, congenital myasthenic syndrome; CNM, centronuclear myopathy; CRM, core-rod myopathy; DA, distal arthrogryposis; DAIPT, arthrogryposis, distal, with impaired proprioception and touch; DM, myotonic dystrophy; EV, Escobar variant; FADS, fetal akinesia deformation sequence; GSD-IV, glycogen storage disease type IV; LAAHD, lethal arthrogryposis with anterior horn cell disease; LCCS, lethal congenital contracture syndrome; LGMD1B, limb-girdle muscular dystrophy type 1B; MDDG, muscular dystrophy-dystroglycanopathy; MPS, multiple pterygium syndrome; MTM, myotubular myopathy; MWKS, Marden-Walker syndrome; NA, not available; NEM, nemaline myopathy; SMA, spinal muscular atrophy; WWS, Walker-Warburg syndrome; XL, X linked; XMEA, X linked myopathy with excessive autophagy.