Inversion duplication of the short arm of chromosome 8: Clinical data on seven patients and review of the literature

Abstract

We report on clinical and cytogenetic data on 5 children and 2 adults with a de novo inverted duplication of the short arm of chromosome 8, and we give a review of 26 patients from the literature. The clinical picture in young children is characterized by minor facial anomalies, hypotonia, and severe developmental delay. In older patients the facial traits are less characteristic, spastic paraplegia develops, and severe orthopedic problems are frequent. Psychomotor retardation is always severe-to-profound. Duplication of 8p21-p22 results in a clinically recognizable multiple congenital anomalies/mental retardation (MCA/MR) syndrome. It is shown that in all patients examined, the duplication was accompanied by a deletion of the most terminal part of 8p.

Trisomy 8p (p11.2-pter) due to maternal translocation t(8;13)(p11;p12) in a child with dysmorphic features

“…Multiple patients with duplication and trisomy of 8p have been reported. [3][4][5][6][7] Many of the previously reported clinical finding were similar.…”

“…In some of those patients, prominent forehead, high arched palate, large mouth with a thin upper lip, malformed and/or apparently lowset ears, broad nasal bridge, dental and skeletal abnormalities, and joint laxity were noted. de DieSmulders et al [4] reported on five children and two adults with duplication of 8p. They found that minor facial anomalies, hypotonia, and severe developmental delay were noticeable in the children, while in older patients the facial traits were less characteristic.…”

A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

“…In fact, some of them, originally interpreted as direct duplications on pure cytogenetic analysis, turned out to be complex rearrangements after proper molecular analysis showing not only a duplicated but also a deleted region. The studies on the inv dup(8p), a recurrent rearrangement associated with a rather characteristic syndrome, 9 revealed that it derives by nonallelic homologous recombination between lowcopy repeats. 7,8,10 Other examples of inv dup are those concerning 1q, 11,12 24 suggesting that the mechanism responsible for the inv dup(8p) can be generalized to all inverted duplications.…”

A Novel 1.0 Mb Duplication of Chromosome 8p22-21.3 in a Patient With Autism Spectrum Disorder

“…14 The clinical picture of patients with duplication of much of 8p was described as a recognizable multiple congenital anomalies such as facial anomalies, hypotonia, structural brain abnormalities, and mental retardation syndrome while profound orthopedic problems, spastic paraplegia, frequently develop in elder patients. [22][23][24] In the database of DECIPHER v8.7, there were 2 cases having a chromosomal aberration mostly analogous to us. One case (Patient 249443) had a 3.41 Mb duplication at 8p22 to 8p21.3 (chr8:18403254-21816649, encompassing 11 genes [ATP6V1B2 (ATPase, H+ transporting, lysosomal, V1 subunit B2), CSGALNACT1, DOK2 (Docking protein 2), GFRA2 (GDNF family receptor alpha 2), INTS10 (Integrator complex subunit 10), LPL (Lipoprotein lipase), LZTS1 (Leucine zipper, putative tumor suppressor 1), PSD3, SH2D4A, SLC18A1 (Solute carrier family 18 member 1), and XPO7 (Exportin 7)], inheritance unknown), with the phenotypes such as autism, inguinal hernia, intellectual disability, long face, macrocephaly, macrotia, proportionate short stature, and seizures; the other (Patient 249579) also had a 3.41 Mb duplication at 8p22 to 8p21.3 (chr8:18403338-21816628, encompassing genes the same as above, inheritance unknown), with a clinical picture of autism, brachycephaly, cryptorchidism, intellectual disability, proptosis, short philtrum, short toe, spasticity, and upslanted palpebral fissure.…”