[en] Adrenal hypoplasia congenita (AHC) is a rare disease. The X-linked form of AHC is caused by deletions or mutations in DAX1 gene and has a variable clinical presentation. To date, no data on X-linked AHC in central Africa are available. Here, we report a Congolese pedigree with several cases of unexplained deaths of male infants. A careful analysis of the pedigree of this family lead to the recognition of an X-linked inheritance pattern, with subsequent confirmation in a female heterozygous carrier of a DAX1 missense mutation c.1274G>T, (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing country, since the manifestations of AHC overlap with those of the much more frequently occurring infections; darkening of the skin is difficult to evaluate and there is a lack of access to routine endocrinological testing. The diagnosis was eventually made based on the family pedigree, evoking an X-linked inheritance pattern. This illustrates the necessity for medical and clinical genetics to be part of the curriculum of medical school in developing countries.
Achermann, J.C., Meeks, J.J., Larry Jameson, J., Phenotypic spectrum of mutations in DAX-1 and SF-1 (2001) Molecular and Cellular Endocrinology, 185 (1-2), pp. 17-25. , DOI 10.1016/S0303-7207(01)00619-0, PII S0303720701006190
Guo, W., Burris, T.P., McCabe, E.R., Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary- adrenal/gonadal axis (1995) Biochem Mol Med, 56 (1), pp. 8-13. , 8593542 10.1006/bmme.1995.1049 1:CAS:528:DyaK2MXpsFensb4%3D
Guo, W., Mason, J.S., Stone Jr., C.G., Morgan, S.A., Madu, S.I., Baldini, A., Lindsay, E.A., Horlick, M.N., Diagnosis of X-linked adrenal hypoplasia congenita by mutation analysis of the DAX1 gene (1995) JAMA, 274 (4), pp. 324-330. , 7609262 10.1001/jama.1995.03530040052040 1:CAS:528:DyaK2MXnt1yksLw%3D
Lawn, J.E., Kerber, K., Enweronu-Laryea, C., Cousens, S., 3.6 million neonatal deaths-what is progressing and what is not? (2010) Semin Perinatol, 34 (6), pp. 371-386. , 21094412 10.1053/j.semperi.2010.09.011
Li, N., Liu, R., Zhang, H., Yang, J., Sun, S., Zhang, M., Liu, Y., Li, X., Seven novel DAX1 mutations with loss of function identified in Chinese patients with congenital adrenal hypoplasia (2010) J Clin Endocrinol Metab, 95 (9), pp. 104-E111. , 20573681 10.1210/jc.2009-2408
Limal, J.-M., Bouhours-Nouet, N., Rouleau, S., Gatelais, F., Coutant, R., Acute adrenal insufficiency in the newborn (2006) Archives de Pediatrie, 13 (10), pp. 1358-1363. , DOI 10.1016/j.arcped.2006.07.016, PII S0929693X06004027
Lin, L., Gu, W.-X., Ozisik, G., To, W.S., Owen, C.J., Jameson, J.L., Achermann, J.C., Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: Ten years' experience (2006) Journal of Clinical Endocrinology and Metabolism, 91 (8), pp. 3048-3054. , http://jcem.endojournals.org/cgi/reprint/91/8/3048, DOI 10.1210/jc.2006-0603
Merke, D.P., Tajima, T., Baron, J., Cutler Jr., G.B., Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene (1999) New England Journal of Medicine, 340 (16), pp. 1248-1252. , DOI 10.1056/NEJM199904223401605
Ostermann, S., Salvi, R., Lang-Muritano, M., Voirol, M.J., Puttinger, R., Gaillard, R.C., Schoenle, E., Pralong, F.P., Importance of genetic diagnosis of DAX-1 deficiency: Example from a large, multigenerational family (2006) Horm Res, 65 (4), pp. 163-168. , 16514244 10.1159/000091831 1:CAS:528:DC%2BD28XjslKktro%3D
Ozer, E.A., Kaya, A., Yildirimer, M., Guler, O., Can, S., Aydinlioglu, H., A novel DAX1 gene mutation in a Turkish infant with X-linked adrenal hypoplasia congenita (2009) Eur J Pediatr, 168 (3), pp. 367-369. , 18604556 10.1007/s00431-008-0778-y
Pelissier, P., Merlin, E., Prieur, F., David, M., Malpuech, G., Forest, M.G., Morel, Y., Stephan, J.-L., Adrenal hypoplasia congenita: Four new cases in children (2005) Archives de Pediatrie, 12 (4), pp. 380-384. , DOI 10.1016/j.arcped.2005.01.007
Phelan, J.K., Mccabe, E.R.B., Mutations in NROB1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita (2001) Human Mutation, 18 (6), pp. 472-487. , DOI 10.1002/humu.1225
Shaikh, M.G., Boyes, L., Kingston, H., Collins, R., Besley, G.T., Padmakumar, B., Ismayl, O., Clayton, P.E., Skewed X inactivation is associated with phenotype in a female with adrenal hypoplasia congenita (2008) J Med Genet, 45 (9), p. 1. , 18762570 10.1136/jmg.2007.055129 1:STN:280:DC%2BD1crntlKiuw%3D%3D
Wheeler, B., George, P.M., MacKenzie, K., Hunt, P., Potter, H.C., Florkowski, C.M., Three cases of congenital adrenal hypoplasia with novel mutations in the (NROB1) DAX-1 gene (2008) Ann Clin Biochem, 45 (PART 6), pp. 606-609. , 18941128 10.1258/acb.2008.008038 1:CAS:528:DC%2BD1MXps1Cgtg%3D%3D
Yang, Y., Sujan, S., Sun, F., Zhang, Y., Jiang, Y., Song, J., Qin, J., Wu, X., Acute Metabolic Crisis Induced By Vaccination in Seven Chinese Patients (2006) Pediatric Neurology, 35 (2), pp. 114-118. , DOI 10.1016/j.pediatrneurol.2005.12.004, PII S0887899406000440
Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T.M., Guioli, S., Guo, W., Lalli, E., McCabe, E.R., An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita (1994) Nature, 372 (6507), pp. 635-641. , 7990953 10.1038/372635a0 1:CAS:528:DyaK2MXislant78%3D
