Cousin syndrome explained

Cousin syndrome is a genetic condition characterized by short stature at birth, a short neck with low-positioned external ears, as well as congenital malformations of the skeletal system affecting the shoulders, the pelvis, the neck, and the limbs (MIM number 260660).^{[1] [2]} The condition determines physical disability, particularly affecting deambulation, and hearing loss while intelligence is not affected.

The condition was originally described in 1982 by Jacques Cousin, physician in Lilles, France, and colleagues as "familial pelvi-scapular dysplasia with dwarfism and dysmorphisms".^[3] Some sporadic patients reported in the medical literature as "pelvic-shoulder dysplasia" or similar diagnoses may in fact have had Cousin syndrome. In 2008, the group of Andrea Superti-Furga showed that the condition was caused by biallelic inactivating variants in the gene coding for the T-box transcription factor, TBX15.^[4] They also proposed to name the condition "Cousin syndrome" because the name "pelviscapular dysplasia" is too restrictive. The incidence of the condition is not known but it seems to be very rare, with only a single further molecularly confirmed individual reported in 2015.^[5] An important differential diagnosis in the newborn and infant is campomelic dysplasia, where hypoplasia of the scapulae and of the iliac bones with femoral dislocation may also occur. Campomelic dysplasia, caused by monoallelic variants in and around the SOX9 gene, is less rare than Cousin syndrome.^[6]

Notes and References

1. Web site: OMIM Entry - # 260660 - COUSIN SYNDROME. www.omim.org.
2. Web site: Cousin syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. rarediseases.info.nih.gov.
3. Cousin J, Walbaum R, Cegarra P, Huguet J, Louis J, Pauli A, Fournier A, Fontaine G. Dysplasie pelvi-scapulaire familiale avec anomalies épiphysaires, nanisme et dysmorphies: un nouveau syndrome? [Familial pelvi-scapulary dysplasia with anomalies of the epiphyses, dwarfism and dysmorphy: a new syndrome? (author's transl)]. Arch Fr Pediatr. 1982 Mar;39(3):173-5. French. PMID 7103674.
4. Lausch E, Hermanns P, Farin HF, Alanay Y, Unger S, Nikkel S, Steinwender C, Scherer G, Spranger J, Zabel B, Kispert A, Superti-Furga A . TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome . American Journal of Human Genetics . 83 . 5 . 649–55 . November 2008 . 19068278 . 2668032 . 10.1016/j.ajhg.2008.10.011 .
5. Dikoglu E, Simsek-Kiper PO, Utine GE, Campos-Xavier B, Boduroglu K, Bonafé L, Superti-Furga A, Unger S. Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the cause of Cousin syndrome. Am J Med Genet A. 2013 Dec;161A(12):3161-5. doi: 10.1002/ajmg.a.36173. Epub 2013 Aug 16. PMID 24039145.
6. Unger S, Scherer G, Superti-Furga A. Campomelic Dysplasia. 2008 Jul 31 [Updated 2021 Mar 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1760/