• Journal of Interdisciplinary Genomics
• /
• v.6 no.1
• /
• pp.1-5
• /
• 2024

Chromosome 22 is an acrocentric chromosome containing 500-600 genes, representing 1.5%-2% of the total DNA in cells. It was the first human chromosome to be fully sequenced by the Human Genome Project. Several syndromes involving the partial deletion or duplication of chromosome 22 are well descibed, including 22q11.2 deletion syndrome, 22q11.2 duplication syndrome, 22q11.2 distal deletion syndrome, Phelan-McDermid syndrome caused by a 22q13 deletion or pathogenic variant in SHANK3, and cat-eye syndrome caused by a 22 pter-q11 duplication. This review aims to provide concise information on the clinical characteristics of these syndromes. In particular, the similarities in features among these syndromes, genetic basis, and standard detection techniques are described, providing guidance for diagnosis and genetic counselling.

• Journal of Genetic Medicine
• /
• v.18 no.2
• /
• pp.110-116
• /
• 2021

Microdeletions of chromosome 22q11.2 are one of the most common microdeletions occurring in humans, and is known to be associated with a wide range of highly variable features. These deletions occur within a cluster of low copy repeats (LCRs) in 22q11.2, referred to as LCR22 A-H. DiGeorge (DGS)/velocardiofacial syndrome is the most prevalent form of a 22q11.2 deletions, caused by mainly proximal deletions between LCR22 A and D. As deletions of distal portion to the DGS deleted regions has been extensively studied, the recurrent distal 22q11.2 microdeletions distinct from DGS has been suggested as several clinical entities according to the various in size and position of the deletions on LCRs. We report a case of long-term follow-up of a female diagnosed with a 22q11.2 distal deletion syndrome, identified a deletion of 1.9 Mb at 22q11.21q11.23 (chr22: 21,798,906-23,653,963) using single nucleotide polymorphism array. This region was categorized as distal deletion type of 22q11.2, involving LCR22 D-F. She was born as a preterm, low birth weight to healthy non-consanguineous Korean parents. She showed developmental delay, growth retardation, dysmorphic facial features, and mild skeletal deformities. The patient underwent a growth hormone administration due to growth impairment without catch-up growth. While a height gain was noted, she had become overweight and was subsequently diagnosed with pre-diabetes. Our case could help broaden the genetic and clinical spectrum of 22q11.2 distal deletions.

• Journal of Genetic Medicine
• /
• v.10 no.2
• /
• pp.120-123
• /
• 2013

This report describes three cases of 22q11.2 deletion syndrome (22q11.2DS) diagnosed by array comparative genomic hybridization with final adult height and bone phenotype. The cases involved a 57-year-old woman with hypocalcemic seizure, an 18-year-old man with short stature, and a 24-year-old woman incidentally diagnosed as 22q11.2DS. The first two patients revealed short stature and low bone mineral density, and their deletion sites included the $TBX_1$. The third patient had normal stature and normal bone mineral density, and the deletion site did not include the $TBX_1$. The deletion of specific genes including the $TBX_1$ could be an important factor of skeletal development including height and bone mineral density of 22q11.2DS.

• Journal of Genetic Medicine
• /
• v.12 no.1
• /
• pp.57-60
• /
• 2015

CHARGE syndrome (coloboma, heart defects, atresia choanae, retarded growth and development, genital hypoplasia, and ear abnormalities) is characterized by multiple malformations and is diagnosed using distinct consensus criteria. Mutations in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7) are the major cause of CHARGE syndrome. Clinical features of CHARGE syndrome considerably overlap those of 22q11.2 deletion syndrome. Of these features, immunodeficiency and hypocalcemia are frequently reported in patients with 22q11.2 deletion syndrome but are rarely reported in patients with CHARGE syndrome. In this report, we have described the case of a patient with typical phenotypes of 22q11.2 deletion syndrome but without the proven chromosome microdeletion. Mutation analysis of CHD7 identified a pathogenic mutation (c.2238+1G>A) in this patient. To our knowledge, this is the first case of CHARGE syndrome with immunodeficiency and hypocalcemia in Korea. Our observations suggest that mutation analysis of CHD7 should be performed for patients showing the typical phenotypes of 22q11.2 deletion syndrome but lacking the proven chromosome microdeletion.

• Archives of Plastic Surgery
• /
• v.41 no.5
• /
• pp.472-479
• /
• 2014

Background Speech problems are a common clinical feature of the 22q11.2 deletion syndrome. The objectives of this study were to inventory the speech history and current self-reported speech rating of adolescents and young adults, and examine the possible variables influencing the current speech ratings, including cleft palate, surgery, speech and language therapy, intelligence quotient, and age at assessment. Methods In this cross-sectional cohort study, 50 adolescents and young adults with the 22q11.2 deletion syndrome (ages, 12-26 years, 67% female) filled out questionnaires. A neuropsychologist administered an age-appropriate intelligence quotient test. The demographics, histories, and intelligence of patients with normal speech (speech rating=1) were compared to those of patients with different speech (speech rating>1). Results Of the 50 patients, a minority (26%) had a cleft palate, nearly half (46%) underwent a pharyngoplasty, and all (100%) had speech and language therapy. Poorer speech ratings were correlated with more years of speech and language therapy (Spearman's correlation=0.418, P=0.004; 95% confidence interval, 0.145-0.632). Only 34% had normal speech ratings. The groups with normal and different speech were not significantly different with respect to the demographic variables; a history of cleft palate, surgery, or speech and language therapy; and the intelligence quotient. Conclusions All adolescents and young adults with the 22q11.2 deletion syndrome had undergone speech and language therapy, and nearly half of them underwent pharyngoplasty. Only 34% attained normal speech ratings. Those with poorer speech ratings had speech and language therapy for more years.

• Clinical and Experimental Pediatrics
• /
• v.57 no.7
• /
• pp.333-336
• /
• 2014

Reports of constitutional ring chromosome 22, r(22) are rare. Individuals with r(22) present similar features as those with the 22q13 deletion syndrome. The instability in the ring chromosome contributes to the development of variable phenotypes. Central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant tumors, primarily occurring in young children below 3 years of age. The majority of ATRT cases display genetic alterations of SMARCB1 (INI1/hSNF5 ), a tumor suppressor gene located on 22q11.2. The coexistence of a CNS ATRT in a child with a r(22) is rare. We present a case of a 4-month-old boy with 46,XY,r(22)(p13q13.3), generalized hypotonia and delayed development. High-resolution microarray analysis revealed a 3.5-Mb deletion at 22q13.31q13.33. At 11 months, the patient had an ATRT ($5.6cm{\times}5.0cm{\times}7.6cm$) in the cerebellar vermis, which was detected in the brain via magnetic resonance imaging.

• Archives of Plastic Surgery
• /
• v.41 no.4
• /
• pp.344-349
• /
• 2014

Background An abnormally obtuse cranial base angle, also known as platybasia, is a common finding in patients with 22q11.2 deletion syndrome (22q11DS). Platybasia increases the depth of the velopharynx and is therefore postulated to contribute to velopharyngeal dysfunction. Our objective was to determine the clinical significance of platybasia in 22q11DS by exploring the relationship between cranial base angles and speech resonance. Methods In this retrospective chart review at a tertiary hospital, 24 children (age, 4.0-13.1 years) with 22q11.2DS underwent speech assessments and lateral cephalograms, which allowed for the measurement of the cranial base angles. Results One patient (4%) had hyponasal resonance, 8 (33%) had normal resonance, 10 (42%) had hypernasal resonance on vowels only, and 5 (21%) had hypernasal resonance on both vowels and consonants. The mean cranial base angle was $136.5^{\circ}$ (standard deviation, $5.3^{\circ}$; range, $122.3-144.8^{\circ}$). The Kruskal-Wallis test showed no significant relationship between the resonance ratings and cranial base angles (P=0.242). Cranial base angles and speech ratings were not correlated (Spearman correlation=0.321, P=0.126). The group with hypernasal resonance had a significantly more obtuse mean cranial base angle ($138^{\circ}$ vs. $134^{\circ}$, P=0.049) but did not have a greater prevalence of platybasia (73% vs. 56%, P=0.412). Conclusions In this retrospective chart review of patients with 22q11DS, cranial base angles were not correlated with speech resonance. The clinical significance of platybasia remains unknown.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.14 no.2
• /
• pp.163-167
• /
• 2014

DiGeorge syndrome is a disorder caused by microdeletion in chromosome 22q11.2 with various abnormalities including cardiac anomaly, facial dysmorphism, thymic and parathyroid hypoplasia, cleft palate and immune dysfunction. The frequency of hypocalcemia caused by hypoparathyroidism is known to be approximately 60% of DiGeorge syndrome. It is known that the disorder mostly occurs in the neonatal period and the symptoms are improved afterwards. Herein we report a case of DiGeorge syndrome only accompanied by hypocalcemia caused by hypoparathyroidism without other abnormalities. She was first diagnosed only at the age of 22 with basal ganglia calcification that had been discovered in brain CT (Computed tomography).

• Clinical and Experimental Pediatrics
• /
• v.59 no.sup1
• /
• pp.25-28
• /
• 2016

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3, RAB, RABL2B, and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.

• Journal of Genetic Medicine
• /
• v.11 no.2
• /
• pp.79-82
• /
• 2014

Mowat-Wilson syndrome is an extremely rare genetic disease that is characterized by intellectual disability, facial dysmorphism, Hirschsprung's disease, and other congenital anomalies. This disorder is caused by heterozygous mutations or deletions in the zinc finger E-box-binding homeobox-2 gene (ZEB2). Thus far, approximately 200 cases of Mowat-Wilson syndrome have been reported worldwide. In Korea, only one case with a 2q22 deletion, which also affects ZEB2, has been previously reported. Here, we describe a patient with Mowat-Wilson syndrome who presented with developmental delays, typical facial dysmorphism, and Hirschsprung's disease. Molecular analysis of ZEB2 identified a novel heterozygous mutation at c.190dup ($p.S64Kfs^*6$). To our knowledge, this is the second report of a Korean patient with Mowat-Wilson syndrome that has been confirmed genetically.