Acquired monosomy 7 myelodysplastic syndrome in a child with clinical features suggestive of dyskeratosis congenita and IMAGe association

Abstract

We describe a case of acquired monosomy 7 myelodysplastic syndrome (MDS) in a boy with congenital adrenocortical insufficiency, genital anomalies, growth delay, skin hyperpigmentation, and chronic lung disease. Some of his clinical manifestations were suggestive of dyskeratosis congenita (DC), while other features resembled IMAGe association. DC has been linked to mutations in telomere maintenance genes. The genetic basis of IMAGe association is unknown, although mice harboring a mutation in a telomere maintenance gene, Tpp1, have adrenal hypoplasia congenita. We considered the possibility that this patient has a defect in telomere function resulting in features of both DC and IMAGe association.

An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function

“…Nevertheless, these patients present unusually identical syndromes. Potentially similar cases with this disorder have previously been reported in the literature (Le and Kutteh, 1996;McDonald et al, 2010), albeit without direct confirmation of the genetic links to SAMD9 at the time. The expression of these disease variants in the presence of the wild-type (wt) SAMD9 protein consistently leads to growth restriction in cultured cells (Narumi et al, 2016), suggesting that there is a dominant feature for these mutant proteins compared with the normal function of SAMD9.…”

Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans

“…Three case reports of children with intrauterine growth restriction (IUGR), congenital adrenal insufficiency, gonadal failure, and monosomy 7 have been published in the last 20 years (12–14). These children also developed MDS, presumably secondary to the monosomy 7, but the interrelation of these features was not understood.…”

Myelodysplastic Disorders, Monosomy 7

“…Viral infections including Epstein-Barr virus (EBV) may contribute to the pathogenesis of MDS by stimulating a preexisting clone and may induce certain genetic mutations [33]. Chromosome 7 abnormalities, monosomy 7 and del (7q), are common cytogenetic abnormalities in MDS and they are found in 31% of children with myeloid neoplasms [22,71]. They are characterized by ineffective erythropoiesis, BM dysplasia, and increased risk of leukemic transformation [22].…”

“…Chromosome 7 abnormalities, monosomy 7 and del (7q), are common cytogenetic abnormalities in MDS and they are found in 31% of children with myeloid neoplasms [22,71]. They are characterized by ineffective erythropoiesis, BM dysplasia, and increased risk of leukemic transformation [22]. Monosomy 7 is the most common chromosomal abnormality in children with MDS [33,71].…”