Combined MECP2 duplication syndrome and ADNP syndrome in a Chinese boy: a case report and literature review

Abstract

Abstract Background Methyl-CpG-binding protein 2 (MECP2) acts as a transcriptional repressor or activator regulating the genes associated with nerve system development. The increased copy number of MECP2 can cause a new X‑linked intellectual disability syndrome named MECP2 duplication syndrome (MDS), which is characterized by a broad range of neurodevelopmental abnormalities, as well as hypotonia, recurrent respiratory infections, and facial dysmorphism. ADNP syndrome is caused by heterozygous de novo mutations in the Activity Dependent Neuroprotective Protein (ADNP) gene, which is characterized by global developmental delay, intellectual disability, language impairment, autism spectrum, and variable extraneurologic features. We reported here the first infant case combined MDS and ADNP syndrome. Case presentation A 6-month boy was hospitalized with a complaint of cough and fever for 7 days. He was born at 40 weeks of gestation with intrauterine growth retardation. He had pneumonia twice since birth, at 1-month and 4-month, respectively. He showed obviously weight and height growth retardation since birth. His motor developmental milestone was obviously delayed. Physical examination revealed no obviously abnormal dysmorphic features. Except for hypotonia, no other neurodevelopmental or ophthalmologic deficits were observed. Genetic analysis revealed that the boy carried a chromosome g.151283637_154348425dup, this area contains Xq28 region (includes MECP2). The boy also carried a de novo ADNP variant heterozygously, c.2194_2197del (p.Leu732MetfsTer20), in exon 5. He fulfilled the diagnostic criteria of MDS and ADNP syndrome. Conclusion We identified a de novo X chromosome g.151283637_154348425dup and a de novo c.2194_2197del (p.Leu732MetfsTer20) in ADNP gene, in a 6-month boy with clinical features of recurrent respiratory infections, growth retardation and hypotonia in China. We reported here the first infant case combined MDS and ADNP syndrome.