TY - JOUR
T1 - Central 22q11.2 Deletions
AU - Rump, Patrick
AU - de Leeuw, Nicole
AU - van Essen, Anthonie J.
AU - Verschuuren - Bemelmans, Corien C.
AU - Veenstra-Knol, Hermine E.
AU - Swinkels, Marielle E. M.
AU - Oostdijk, Wilma
AU - Ruivenkamp, Claudia
AU - Reardon, Willie
AU - de Munnik, Sonja
AU - Ruiter, Mariken
AU - Frumkin, Ayala
AU - Lev, Dorit
AU - Evers, Christina
AU - Sikkema-Raddatz, Birgit
AU - Dijkhuizen, Trijnie
AU - van Ravenswaaij-Arts, Conny M.
PY - 2014/11
Y1 - 2014/11
N2 - 22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a deletion resulting from a recombination of low copy repeat blocks LCR22-A and LCR22-D. Loss of the TBX1 gene is considered the most important cause of the phenotype. A limited number of patients with smaller, overlapping deletions distal to the TBX1 locus have been described in the literature. In these patients, the CRKL gene is deleted. Haploinsufficiency of this gene has also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To distinguish these deletions (comprising the LCR22-B to LCR22-D region) from the more distal 22q11.2 deletions (located beyond LCR22-D), we propose the term central 22q11.2 deletions. In the present study we report on 27 new patients with such a deletion. Together with information on previously published cases, we review the clinical findings of 52 patients. The prevalence of congenital heart anomalies and the frequency of de novo deletions in patients with a central deletion are substantially lower than in patients with a common or distal 22q11.2 deletion. Renal and urinary tract malformations, developmental delays, cognitive impairments and behavioral problems seem to be equally frequent as in patients with a common deletion. None of the patients had a cleft palate. Patients with a deletion that also encompassed the MAPK1 gene, located just distal to LCR22-D, have a different and more severe phenotype, characterized by a higher prevalence of congenital heart anomalies, growth restriction and microcephaly. Our results further elucidate genotype-phenotype correlations in 22q11.2 deletion syndrome spectrum. (c) 2014 Wiley Periodicals, Inc.
AB - 22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a deletion resulting from a recombination of low copy repeat blocks LCR22-A and LCR22-D. Loss of the TBX1 gene is considered the most important cause of the phenotype. A limited number of patients with smaller, overlapping deletions distal to the TBX1 locus have been described in the literature. In these patients, the CRKL gene is deleted. Haploinsufficiency of this gene has also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To distinguish these deletions (comprising the LCR22-B to LCR22-D region) from the more distal 22q11.2 deletions (located beyond LCR22-D), we propose the term central 22q11.2 deletions. In the present study we report on 27 new patients with such a deletion. Together with information on previously published cases, we review the clinical findings of 52 patients. The prevalence of congenital heart anomalies and the frequency of de novo deletions in patients with a central deletion are substantially lower than in patients with a common or distal 22q11.2 deletion. Renal and urinary tract malformations, developmental delays, cognitive impairments and behavioral problems seem to be equally frequent as in patients with a common deletion. None of the patients had a cleft palate. Patients with a deletion that also encompassed the MAPK1 gene, located just distal to LCR22-D, have a different and more severe phenotype, characterized by a higher prevalence of congenital heart anomalies, growth restriction and microcephaly. Our results further elucidate genotype-phenotype correlations in 22q11.2 deletion syndrome spectrum. (c) 2014 Wiley Periodicals, Inc.
KW - 22q11
KW - 2
KW - deletion
KW - atypical
KW - distal
KW - TBX1
KW - CRKL
KW - MAPK1
KW - CARDIO-FACIAL SYNDROME
KW - DISTAL DELETION
KW - DIGEORGE-SYNDROME
KW - CHROMOSOME 22Q11
KW - DIGEORGE/VELOCARDIOFACIAL SYNDROME
KW - VELOCARDIOFACIAL SYNDROME
KW - PHENOTYPIC VARIABILITY
KW - DEL22Q11 SYNDROME
KW - HEART-DEFECTS
U2 - 10.1002/ajmg.a.36711
DO - 10.1002/ajmg.a.36711
M3 - Article
SN - 1552-4841
VL - 164
SP - 2707
EP - 2723
JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
IS - 11
ER -