X-linked adrenal hypoplasia congenita: a novel DAX1 missense mutation and challenges for clinical diagnosis in Africa

Abstract

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.

Williams–Beuren syndrome: pitfalls for diagnosis in limited resources setting

“…Such overlap of genetic disease with an infectious disease is expected to be frequent in the developing world, where infections represent the major medical problem. As previously reported, infections are major cause for misdiagnosis of genetic diseases in developing countries . The present report supports the assumption that infections constitutes a major pitfall for genetic diagnosis and warns for clinicians working in developing world that a genetic disease may be masked by a intercurrent infectious disease.…”

Preaxial Polydactyly of the Foot: Variable Expression of Trisomy 13 in a Case from Central Africa

“…The case reported here is the first one with trisomy 13 to be reported in Central Africa (with the exception of a report in 1968) [9]. This probably reflects the current lack of teaching and thus interest and knowledge in human genetics and syndromology [23]. Whereas, in most industrialized countries, trisomy 13 is diagnosed prenatally, the vast majorities of pregnant women in Central Africa currently do not have access to prenatal ultrasound follow-up and are thus confronted with serious emotional distress when facing an unexpected polymalformed newborn.…”

Wolf-Hirschhorn Syndrome: Clinical and Genetic Data from a First Case Diagnosed in Central Africa

“…This underlines the urgent need for training in medical genetics and syndromology in Central Africa because currently little awareness and knowledge exists in this field. 29 Author Contributions Sébastien Mbuyi-Musanzayi: clinical examination, treatment of the patient, and redaction of article. Aimé Lumaka: array testing and manuscript correction.…”