%0 Journal Article
%T Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective.
%A Cuinat S
%A Quélin C
%A Effray C
%A Dubourg C
%A Le Bouar G
%A Cabaret-Dufour AS
%A Loget P
%A Proisy M
%A Sauvestre F
%A Sarreau M
%A Martin-Berenguer S
%A Beneteau C
%A Naudion S
%A Michaud V
%A Arveiler B
%A Trimouille A
%A Macé P
%A Sigaudy S
%A Glazunova O
%A Torrents J
%A Raymond L
%A Saint-Frison MH
%A Attié-Bitach T
%A Lefebvre M
%A Capri Y
%A Bourgon N
%A Thauvin-Robinet C
%A Tran Mau-Them F
%A Bruel AL
%A Vitobello A
%A Denommé-Pichon AS
%A Faivre L
%A Brehin AC
%A Goldenberg A
%A Patrier-Sallebert S
%A Perani A
%A Dauriat B
%A Bourthoumieu S
%A Yardin C
%A Marquet V
%A Barnique M
%A Fiorenza-Gasq M
%A Marey I
%A Tournadre D
%A Doumit R
%A Nugues F
%A Barakat TS
%A Bustos F
%A Jaillard S
%A Launay E
%A Pasquier L
%A Odent S
%J J Med Genet
%V 0
%N 0
%D 2024 Jun 7
%M 38849204
%F 5.941
%R 10.1136/jmg-2024-109854
%X <B>BACKGROUND: </B>Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.<BR><B>METHODS: </B>After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.<BR><B>RESULTS: </B>We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.<BR><B>CONCLUSIONS: </B>Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.