A case of ADH5/ALDH2 deficiency combined with 3q29 microduplication syndrome in the Department of Hematology, Beijing Children's hospital was retrospectively analyzed. The child, a 3-year-old girl, had a history of recurrent cutaneous petechias, and multiple episodes of pancytopenia. She was examined for café au lait spots, growth retardation, and microcephaly. Fanconi anemia (FA) was highly suspected according to the clinical manifestations and laboratory tests of the child, and was diagnosed as Amed syndrome combined with 3q29 microduplication syndrome according to the genetic results. Amed syndrome is an autosomal recessive multisystem disorder characterized by global developmental delay, impaired intellectual development, bone marrow failure and myelodysplastic syndrome (MDS) in childhood, and global dysplasia and short stature. The disease is caused by combination mutations of ADH5 and ALDH2 genes, which belongs to a special type of inherited bone marrow failure syndrome (IBMFS). Therefore, for the repeated pancytopenia in childhood, we should be alert to the possibility of congenital bone marrow failure syndrome, improve genetic testing as soon as possible, and carry out hematopoietic stem cell transplantation (HSCT) when necessary. 3q29 microduplication syndrome is mainly due to the delayed development of neurological symptoms. This syndrome may affect the growth and development of children together with ADH5 and ALDH2 genes.

The 3q29 microduplication syndrome is usually associated with an intellectual disability or global developmental delay and mild dysmorphisms. Other comorbid presentations reported in the literature include psychiatric disorders such as behavioral disorders, attention-deficit/hyperactivity disorders, elimination disorders, and autism spectrum disorders. The current case is of an adolescent girl with the 3q29 microduplication syndrome who had a diverse psychiatric presentation. The patient was a 14-year-old girl in institutional care, with a moderate intellectual developmental disorder, major behavioral problems, with auto- and hetero-aggressions and a suspicious trait, who presented with frequent episodes of emotional dysregulation, disorganized speech with derailment, incoherence, perseveration and grossly disorganized behavior. Auditory hallucinations were suspected sometimes but were difficult to evaluate. In our assessment, we were not able to determine a diagnosis because the symptoms do not seem to be defined by any classification. Major pharmacological and non-pharmacological interventions were needed to manage this case.

1q43q44 microdeletion syndrome is characterized by intellectual disability/global developmental delay, epilepsy, dysmorphic facies, stereotypic movement, language delay, recurrent infections, dental anomalies, and hand and foot anomalies. Microcephaly and corpus callosum dysplasia are present in some cases depending on gene content. 3q29 microduplication syndrome is characterized by intellectual disability, language delay, microcephaly, and dental anomalies. We report the first case with 4 de novo copy number variations with clinical features which overlap 1q43q44 microdeletion and 3q29 microduplication syndromes. Our case presented with global developmental delay, epilepsy, recurrent infections, stereotypic movements, speech delay, microcephaly, facial dysmorphism, bilateral clinodactyly, and small puffy feet with metatarsus varus; however, she had no corpus callosum dysplasia. Our case highlights the role of multiple copy number variations in the occurrence of a certain phenotype. Moreover, it supports the theory that the loss of HNRNPU gene function cannot explain the occurrence of microcephaly and abnormalities of the corpus callosum in 1q43q44 microdeletion syndrome.