A case report of concomitant myopathy, adrenal insufficiency, and mental retardation linked with deletion of Xp21

Contiguous gene syndromes (CGS) are the disorders caused by chromosomal abnormalities: deletions, duplications, or other complex rearrangements that alter gene dosage. Initially, before their chromosomal nature is elucidated, they may be misdiagnosed as monogenic disorders depending on the leading clinical symptom cluster. The altered chromosomal region in individuals with this condition is typically less than 5 Mb in size and sometimes cannot be identified by conventional karyotyping. Patients present with signs of the diseases associated with each individual monogenic disorder. The Xp21-linked genetic syndrome, or glycerol kinase deficiency (GKD) (MIM 300474), is an example of this syndrome [1–3]. The genes coding for glycerol kinase (GK), congenital adrenal hypoplasia (NR0B1), and dystrophin (DMD) follow each other in the Xp21.2—p21.3 region. Deletions of an X-chromosome region may cause several monogenic disorders in one patient, including primary adrenal insufficiency and hypogonadotropic hypogonadism as a result of deletion in the NR0B1 gene, Duchenne muscular dystrophy (or a milder form, Becker muscular dystrophy) resulting from deletion in the dystrophin gene, and mental retardation as a result of deletion in the glycerol kinase gene.

We report a case of concomitant myopathy, adrenal insufficiency, and mental retardation linked with deletion of Xp21.

adrenal insufficiency, duchenne muscular dystrophy, glycerol kinase deficiency, deletion of Xp21

1. Mccabe ER, Fennessey PV, Guggenheim MA, et al. Human glycerol kinase deficiency with hyperglycerolemia and glyceroluria. Biochem Biophys Res Commun. 1977;78(4):1327-1333.

2. Guggenheim MA, Mccabe ER, Roig M, et al. Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities. Ann Neurol. 1980;7(5):441-449. doi: 10.1002/ana.410070509

3. Wieringa B, Hustinx T, Scheres J, et al. editors. Glycerol kinase deficiency syndrome explained as X-chromosomal deletion. In: Cytogenetics and cell genetics. Basel (Switzerland): Karger; 1985.

4. Schmickel RD. Contiguous gene syndromes: a component of recognizable syndromes. J Pediatr. 1986;109(2):231-241.

5. Patil S, Bartley J, Murray J, et al. editors. X-linked glycerol kinase, adrenal hypoplasia and myopathy maps at xp21. Cytogenetics and cell genetics. In: Cytogenetics and cell genetics. Basek (Switzerland): Kager; 1985.

6. Stuhrmann M, Heilbronner H, Reis A, et al. Characterisation of a xp21 microdeletion syndrome in a 2-year-old boy with muscular dystrophy, glycerol kinase deficiency and adrenal hypoplasia congenita. Hum Genet. 1991;86(4):414-415.

7. Muscatelli F, Strom TM, Walker AP, et al. Mutations in the DAX-1 gene give rise to both x-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature. 1994;372(6507):672-676. doi: 10.1038/372672a0

8. Falzarano MS, Scotton C, Passarelli C, Ferlini A. Duchenne muscular dystrophy: from diagnosis to therapy. Molecules. 2015;20(10):18168-18184. doi: 10.3390/molecules201018168

9. Aartsma-Rus A, Ginjaar IB, Bushby K. The importance of genetic diagnosis for duchenne muscular dystrophy. J Med Genet. 2016;53(3):145-151. doi: 10.1136/jmedgenet-2015-103387

10. Strehle EM, Straub V. Recent advances in the management of duchenne muscular dystrophy. Arch Dis Child. 2015;100(12):1173-1177. doi: 10.1136/archdischild-2014-307962

11. Hellerud C, Wramner N, Erikson A, et al. Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis. Acta Paediatr. 2004;93(7):911-921. doi: 10.1111/j.1651-2227.2004.tb02689.x

12. Lurquin C, de Smet C, Brasseur F, et al. Two members of the human mageb gene family located in xp21.3 are expressed in tumors of various histological origins. Genomics. 1997;46(3):397-408. doi: 10.1006/geno.1997.5052