Department of Pediatrics, University Children's Hospital, Badajoz, Spain.
University of Extremadura, Badajoz, Spain.
Eur J Med Genet. 2021 Oct;64(10):104307. doi: 10.1016/j.ejmg.2021.104307. Epub 2021 Aug 15.
Metaphyseal anadysplasia is a very rare hereditary skeletal dysplasia with onset occurring normally during the second and third years of life, but unlike many other dysplasias, symptoms appear to resolve by adolescence. Two types exist, the more severe form, type 1, with both autosomal dominant and recessive inheritance due to pathogenic variants in MMP13, whilst type 2, an even rarer form is due to biallelic MMP9 variants. To date, only two metaphyseal anadysplasia type 2 families have been reported. We describe a third family, a young boy, born to consanguineous parents, referred at 19 months old for abnormal gait due to bowed legs. Clinical and radiological examination revealed scoliosis, genu varum and metaphyseal abnormalities. A homozygous MMP9 nonsense variant, NM_004994.2:c.1764G>A; p.(Trp588*) was identified. By the age of 39 months, lower limb alignment and metaphyseal features had already significantly improved and scoliosis had disappeared. This case confirms that biallelic MMP9 variants cause this very rare skeletal dysplasia, metaphyseal anadysplasia type 2 but also shows that the skeletal manifestations can improve within a short period time and at an early age.
干骺发育不良是一种非常罕见的遗传性骨骼发育不良，通常在生命的第二年和第三年开始发病，但与许多其他发育不良不同，症状似乎在青春期前得到缓解。存在两种类型，更为严重的 1 型是常染色体显性和隐性遗传，由 MMP13 的致病性变异引起，而更为罕见的 2 型是由于 MMP9 的双等位基因变异引起。迄今为止，仅报道了两例干骺发育不良 2 型家族。我们描述了第三个家族，一个 19 个月大的男孩，因弯曲腿导致步态异常而由近亲父母转诊。临床和放射学检查显示脊柱侧凸、膝内翻和干骺端异常。发现了一种纯合 MMP9 无义变异，NM_004994.2:c.1764G>A;p.(Trp588*)。到 39 个月时，下肢对线和干骺端特征已经显著改善，脊柱侧凸已经消失。该病例证实双等位基因 MMP9 变异导致这种非常罕见的骨骼发育不良，干骺发育不良 2 型，但也表明骨骼表现可以在短时间内和早期得到改善。
