Tetrasomy 15q26

A number sign (#) is used with this entry because this dysmorphic condition is caused by tetrasomy of chromosome 15q26-qter.

Clinical Features

Levy et al. (2012) reported 4 patients with tetrasomy 15q26 and reviewed the literature describing an additional 10 cases. They compared the tetrasomy phenotype with that of Shprintzen-Goldberg syndrome (182212) and found that the facial gestalt was different. All 4 cases of Levy et al. (2012) had no evidence of mosaicism. Among all reports there were an equal number of males and females. The ages at which the patients were evaluated ranged from 9 to 32 years for the cases of Levy et al. (2012), and from in utero to 10 years for the reviewed cases. The in utero reports noted in utero growth restriction (IUGR); all other patients had normal or increased birth weight, with normal or increased birth length. All 4 cases reported by Levy et al. (2012) and an additional 4 patients had a typical craniofacial gestalt which included low-set dysplastic ears, hypertelorism and/or telecanthus, downslanting palpebral fissures, coarse asymmetric facies, prominent nose with broad nasal root, and a prominent chin. All patients in whom evaluation was possible had developmental delay. The 4 patients reported by Levy et al. (2012) and the majority of the others had craniosynostosis and/or skull deformity. Most had micro/retrognathia. Central nervous system (CNS) abnormalities were present in 6 of 7 in whom evaluation was performed and included hydrocephalus, Dandy-Walker malformation, syrinx, and brain atrophy. None had hernia. The majority had arachnodactyly and/or camptodactyly/contractures. Only 1 patient had a pectus abnormality. None of those reported by Levy et al. (2012), but 3 of the others, had a congenital heart defect. All 4 of the patients reported by Levy et al. (2012) but only 1 of the others had kyphosis/scoliosis. The vast majority had renal anomalies including horseshoe kidneys, obstructive uropathy, and hydronephrosis; 1 patient had bilateral Wilms tumor. Levy et al. (2012) concluded that the hallmark features of tetrasomy 15q26 include severe developmental delay, craniosynostosis, marfanoid habitus, coarse asymmetric facies, prominent nose with broad nasal root, and prominent chin. Renal anomalies strongly implicate aneusomy of distal 15q, but may be absent if the breakpoint lies distal to 15q25.3. Levy et al. (2012) noted clinical similarity between tetrasomy 15q26, Shprintzen-Goldberg syndrome, and Loeys-Dietz syndrome (see 609192) and recommended that all 3 of these syndromes be included in the differential diagnosis.

Cytogenetics

Four patients described by Levy et al. (2012) had tetrasomy 15q26 in the form of an inverted duplicated supernumerary chromosome with a neocentromere. In all cases the duplicated part of 15q ended at position 100,276,767, but the start sites of the duplication varied, with the most proximal being at 82,937,406, resulting in a tetrasomic region of 17.3 Mb (15q25.2-q26.3), and the most distal at 88,847,491, resulting in a tetrasomic region of 11.4 Mb (15q26.1-q26.3).