LAUSR

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.