Published: 2022-05-25

De novo SOX6 variant: Tolchin-Le Caignec syndrome

Rahul Sinha, Sonali Singh, Gautam Kamila


Tolchin-Le Caignec syndrome (TOLCAS) is a developmental disorder characterized by intellectual impairment and behavioural issues such as autism, hyperactivity, aggressive episodes and mood swings and lack of sleep. The other manifestations include osteochondroma, craniosynostosis, dysmorphic facies, arachnodactyly, prominent occiput and bitemporal narrowing. We reported this rare syndrome in a 5 and half year old female child who presented with global developmental delay (language and cognitive predominant), autistic features, hyperactivity, aggressive behaviour and dysmorphism (high forehead, bitemporal narrowing, micrognathia, low set ears, hypertelorism, wide nasal bridge, scaphocephaly, clinodactyly). The whole exome sequencing detected de novo heterozygous missense pathogenic variant c.1378A>C, p. (Asn460His) in exon 11 of SOX6 gene with no similar variant found in either of the parents   confirmed the diagnosis of TOLCAS. This rare case report highlighted the phenotypic variation due to SOX6 gene mutation which the clinician should be aware of while dealing with dysmorphic child with cognitive and language delay with autistic features.


Autistic, Dysmorphism, Hyperactivity, Developmental delay

Full Text:



Tolchin D, Yeager JP, Prasad P, Dorrani N, Russi AS, Martinez-Agosto JA et al. De novo SOX6 variants cause a neurodevelopmental syndrome associated with ADHD, craniosynostosis, and osteochondromas. Am J Hum Genet. 2020;106:830-45.

Angelozzi M, Lefebvre V. SOXopathies: growing family of developmental disorders due to SOX mutations. Trends Genet. 2019;35:658-71.

Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Münsterberg A et al. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990;346:245-50.

Cohen-Barak O, Hagiwara N, Arlt MF, Horton JP, Brilliant MH. Cloning, characterization and chromosome mapping of the human SOX6 gene. Gene. 2001;265:157-64.

Lefebvre V, Li P, de Crombrugghe B. A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene. EMBO J. 1998;17:5718-33.

Quiat D, Voelker KA, Pei J, Grishin NV, Grange RW, Bassel-Duby R, Olson EN. Concerted regulation of myofiber-specific gene expression and muscle performance by the transcriptional repressor Sox6. Proc Natl Acad Sci USA. 2011;108:10196-201.

Sluijter JP, van Mil A, van Vliet P, Metz CH, Liu J, Doevendans PA, Goumans MJ. MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler Thromb Vasc Biol. 2010;30:859-68.

Dumitriu B, Patrick MR, Petschek JP, Cherukuri S, Klingmuller U, Fox PL, Lefebvre V. Sox6 cell-autonomously stimulates erythroid cell survival, proliferation, and terminal maturation and is thereby an important enhancer of definitive erythropoiesis during mouse development. Blood. 2006;108:1198-207.

Azim E, Jabaudon D, Fame R, Macklis JD. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. Nat. Neurosci. 2009;12:1238-47.

Batista-Brito R, Rossignol E, Hjerling-Leffler J, Denaxa M, Wegner M, Lefebvre V. The cell-intrinsic requirement of Sox6 for cortical interneuron development. Neuron. 2009;63:466-81.

Stolt CC, Schlierf A, Lommes P, Hillgärtner S, Werner T, Kosian T et al. SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Dev Cell. 2006;11:697-709.