Microduplication of 4p16.3 due to an unbalanced translocation resulting in a mild phenotype

Abstract

With the widespread clinical use of comparative genomic hybridization chromosomal microarray technology, several previously unidentified clinically significant submicroscopic chromosome abnormalities have been discovered. Specifically, there have been reports of clinically significant microduplications found in regions of known microdeletion syndromes. In general, these microduplications have distinct features from those described in the corresponding microdeletion syndromes. We present a 5½-year-old patient with normal growth, borderline normal IQ, borderline hypertelorism, and speech and language delay who was found to have a submicroscopic 2.3 Mb terminal duplication involving the two proposed Wolf-Hirschhorn syndrome (WHS) critical regions at chromosome 4p16.3. This duplication was the result of a maternally inherited reciprocal translocation involving the breakpoints 4p16.3 and 17q25.3. Our patient's features are distinct from those described in WHS and are not as severe as those described in partial trisomy 4p. There are two other patients in the medical literature with 4p16.3 microduplications of similar size also involving the WHS critical regions. Our patient shows clinical overlap with these two patients, although overall her features are milder than what has been previously described. Our patient's features expand the knowledge of the clinical phenotype of a 4p16.3 microduplication and highlight the need for further information about it.

Complex chromosomal rearrangement involving five chromosomes

“…The terminal microduplication of 2.3 Mbp involving the 4p16.3 region has been described previously (Carmany and Bawle, 2011). The clinical features of our patient are similar to their 5½-year-old patient with normal growth, borderline normal IQ, borderline hypertelorism, and speech and language delay.…”

Candidate Genes Associated With Neurological Findings in a Patient With Trisomy 4p16.3 and Monosomy 5p15.2

“…It is characterized by facial dysmorphia, growth retardation, intellectual incapacity, and seizures (Zollino et al, 2008). However, duplication of the WHS critical region is a rare chromosomal condition causing mild clinical phenotypes, such as speech delay, facial dysmorphia, seizures, and delayed neuro and psychomotor development (Patel et al, 1995;Hannes et al, 2010;Carmany and Bawle, 2011;Cyr et al, 2011). However, the phenotypic and cytogenetic variability in affected individuals, such as the low frequency and the large genomic regions that can be altered, make it challenging to identify the candidate genes that contribute to the pathogenesis of these syndromes.…”

Subtelomeric Rearrangements: Presentation of 21 Probands with Emphasis on Familial Cases

“…Patient 19 seems to fit better into 4p16.3 duplication characteristics. [20][21][22] Both cases 11 and 12 presented with chromosome 6pter-p24 deletion syndrome, characterized by ID, ophthalmologic abnormalities, craniofacial dysmorphisms (macrocephaly, prominent forehead, down-slanting palpebral fissures, hypertelorism and depressed nasal bridge), Dandy-Walker malformation, congenital heart defects, hypotonia, hearing loss, and others, with high phenotypic variability. 23,24 The father of case 12 presented the same phenotype as his son.…”