We report the case of a 3-year-old girl with alpha-thalassemia/mental retardation linked to chromosome 16 (ATR-16) syndrome. The patient presented with hypotonia, developmental delay, and characteristic facial features including hypertelorism and a broad nasal bridge. Blood test results indicated microcytic anemia and normal iron status, suggestive of thalassemia. Genetic analysis revealed that the patient harbored a 465 kb deletion in the 16p13.3 region and a 19.4 Mb duplication in the 16q22.1-q24.3 region. The patient presented with rare complications of ATR-16 syndrome, including anal fistula, vesicoureteral reflux (VUR), and patent ductus arteriosus (PDA). Comparison of this case with previously reported patients with pure partial trisomy 16q suggested that the duplicated distal 16q region may be a critical locus associated with VUR and PDA.

We present a case study of a 73-year-old female with a history of pancytopenia. The bone marrow core biopsy was suggestive of a myelodysplastic syndrome, unspecified (MDS-U). Chromosomal analysis of the bone marrow revealed an abnormal karyotype including gain of chromosomes 1, 4, 6, 8, 9, 19, and 20 in addition to loss of chromosomes 11, 13, 15, 16, 17, and 22. Also, additional material of unknown origin was found on 3q, 5p, 9p, 11p, 13p, 14p, and 15p; there were two copies of 19p, a deletion of 8q, and numerous unidentified rings and markers were present. This was characterized as: 75~77,XXX,+1,der(1;6)(p10;p10),add(3)(q27),+4,add(5)(p15.1),+6,+8,del(8)(q24.1),+add(9)(p24),-11,add (11) (p13),-13,add(13)(p10),add(14)(p11.2),-15,add(15)(p11.2), -16,-17,+19,add(19)(p13.3)x2,+20,-22, +0~4r,+4~10mar[cp11]/46,XX[8]. The cytogenetic analysis correlates with the concurrent FISH study which was positive for additional signals of EVI1(3q26.2), TAS2R1 (5p15.31), EGR1 (5q31.2), RELN (7q22), TES (7q31) RUNX1T1 (8q21.3), ABL1 (9q34), KMT2A (11q23), PML (15q24.1), CBFB (16q22), RARA (17q21), PTPRT (20q12), MYBL2 (20q13.12), RUNX1 (21q22.12) and BCR (22q11.2). Hyperdiploid karyotypes within the context of complex structural abnormalities are rare events usually associated with a poor prognosis in MDS.

A 15-month-old boy presented with growth and global developmental delay, feeding difficulties, sleep disturbance and several minor anomalies, including a large anterior fontanel, relative macrocephaly, and a triangular face. Clinical suspicion prompted genetic investigations for Silver-Russell syndrome and related disorders. SNP array analysis led to the diagnosis of an approximately 10-Mb large deletion of the long arm in chromosome 16q22.2q23.3. Interstitial deletions of 16q show a wide variability of related features; however, considering the differences in size and location of the deletions in the known patients, the phenotypic overlap is surprising. Here, we report a novel microdeletion, compare the proband with data from scientific literature and international databases, and discuss possible diagnostic implications.

In partial monosomy of the distal part of chromosome 16q, abnormal facial features, intellectual disability (ID), and feeding dysfunction are often reported. However, seizures are not typical and the majority of them were seizure-free. Here we present the case of a 16q22.2-q23.1 interstitial deletion identified in a male patient with severe ID, facial anomalies including forehead protrusions and flat nose bridge, patent ductus arteriosus, bilateral vocal cord atresia treated by tracheotomy, and West syndrome, which were developed 10 months after birth. Although phenobarbital, sodium valproate (VPA), and zonisamide were not effective as monotherapies or combination therapies, the patient's epileptic seizures and electroencephalogram anomalies disappeared following combined therapy with lamotrigine and VPA. Although WW Domain Containing Oxidoreductase (WWOX), which is known as a cause of autosomal recessive epileptic encephalopathy, was included within the 6.8-Mb deleted region which identified by targeted panel sequencing and validated by chromosomal microarray analysis, no pathogenic variants were detected in the other allele of WWOX. Therefore, it is possible that other genes within or outside of the long deleted region or their interactions may cause West syndrome in this patient.

The widespread availability of comparative genomic hybridization (CGH) array analysis has led to the discovery of several genomic microdeletion-associated syndromes and has identified possible genetic causes for patients with previously unexplained clinical features. We report the case of four unrelated patients who share common clinical characteristics, namely failure to thrive, developmental delay, dysmorphic features, and congenital anomalies. CGH array analysis revealed that all four patients had a de novo microdeletion at 16q22.1. In this case report, we describe the clinical features of these patients and offer possible explanations for how their 16q22.1 microdeletion may account for their symptoms. We also suggest guidelines for the management of 16q22.1 microdeletion based on the phenotypes seen in our patients and the function of the genes affected by this microdeletion.