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A 21q deletion has been associated with a wide range of clinical signs, from very mild to severe phenotypes, and with the progress of genetic technology, more patients with this deletion are being diagnosed. This study reports on a 9-year-old boy with a terminal deletion of 4.5 Mb on chromosome 21 in the locus of chr21: 43531239-48119895 (GRCh37/hg19). Dark skin, a buried penis, small testes, dental caries, microcephaly, a low auricle, mental and intellectual retardation, balance disorder and pituitary and callosum dysplasia were observed. The results of a literature review and observation of similar abnormalities, including hypoplasia of corpus callosum, in two patients with non-overlapping deletion regions suggest that there are multiple gene loci regulating brain development on 21q. By comparing the overlapped deletion region in 21q22.3 cases of brain anomalies and/or gonadal dysgenesis, we concluded there were two overlapped microdeletion regions (chr21:43531239-43792093 and chr21:46625055-46884297) that may be related to brain and gonadal development. The same 16.49 Mb deletion of chr21:31578129-48119895 (GRCh37/hg19) was shared in 10 cases, and 24 cases shared the same 5.59 Mb deletion of chr21:42478130-48119895 (GRCh37/hg19) in DECIPHER (Database of Chromasomal Imbalance and Phenotype in Humans using Ensembl Resources), suggesting these were two commonly deleted regions of pure partial 21q. Those patients with the same breakpoints had different phenotypes suggesting the heterogeneity of 21q deletion.

A Arboleda-Tham syndrome (OMIM#616268) is a newly named neurodevelopmental disorder, which is an autosomal dominant hereditary disease characterized by genetic variants. The clinical manifestations include global developmental delay, primary microcephaly, and craniofacial dysmorphism, as well as more varied features such as feeding difficulties, cardiac defects, and ocular anomalies. Currently, due to restricted knowledge of Arboleda-Tham syndrome and less specific pathological manifestations, it is difficult to diagnose at the early stages of the disease. Here, we present a case with obvious growth retardation and intellectual disability, accompanied by other manifestations including dysmorphic features of the ears, facial dysmorphism, right cryptorchidism, and inguinal hernia. Routine laboratory tests including blood-urine tandem mass spectrometry, urine gas chromatographic mass spectrometry, karyotype, echocardiography, automatic auditory brainstem responses, serum levels of calcium, phosphorus, vitamin D, creatine kinase (CK), and CK isoenzyme (CK-MB), and brain magnetic resonance imaging showed negative results. A de novo heterozygous variant in KAT6A, c.57delA (p.Val20*), was detected by trio-based whole exome sequencing and subsequent validation by Sanger sequencing in the patient, which was absent in both the parents. The patient received rehabilitation and nutritional intervention. The testis reduction and orchiopexy was scheduled when he was 1 year old. Our report extends the phenotype-genotype map of Arboleda-Tham syndrome, and also expands the mutant spectrum of the KAT6A gene. Moreover, this case emphasizes the timely conduction of whole exome sequencing for the early diagnosis of Arboleda-Tham syndrome, and spares patients from meaningless examinations and ineffective treatments.