Confirmation of mosaic trisomy 22 in an infant with failure to thrive

Introduction Chromosome mosaicism is defined as the presence of two or more karyotypically different cell lines in an individual. These two cell lines occur as a post zygotic event but other mechanisms are also described. Mosaicism is associated with the live birth of infants with chromosome anomalies that are not detected in non-mosaic forms and the mosaicism may be present at low levels in tissues making cytogenetic confirmation difficult. In some cases, the mosaicism is confined to a single tissue adding to the complexity of diagnosis. We report a child with clinical features of mosaicism in whom the diagnosis of mosaic trisomy 22 was confirmed.


Introduction
Chromosome mosaicism is defined as the presence of two or more karyotypically different cell lines in an individual 1 .These two cell lines occur as a post zygotic event but other mechanisms are also described 2 .Mosaicism is associated with the live birth of infants with chromosome anomalies that are not detected in non-mosaic forms and the mosaicism may be present at low levels in tissues making cytogenetic confirmation difficult.In some cases, the mosaicism is confined to a single tissue adding to the complexity of diagnosis 3 .We report a child with clinical features of mosaicism in whom the diagnosis of mosaic trisomy 22 was confirmed.

Case report
A 4 ½ year old girl who was the second child of healthy, unrelated parents presented for further evaluation of poor growth.She was born at term with symmetrical intrauterine growth retardation: birth weight 1.8 kg (<-3SD), occipito-frontal circumference (OFC) 31cm (<5 th centile) and length 46cm (<-3SD).She had a cleft of her soft palate which was repaired at nine months of age and ventricular septal defect closed at 10 months of age.She also had severe feeding difficulty associated with severe gastro-esophageal reflux disease and complicated with recurrent aspiration pneumonias necessitating gastrostomy feeding.
On examination, she had severe growth retardation with a weight of 8.8 kg (<-3SD), height of 85cm (<-3SD) and an OFC of 41 cm (<-3 SD).She had linear hypopigmentation along the lines of Blaschko in both upper limbs, left sided facial, limb and trunk hypoplasia [with leg length discrepancy of 3 cm] and a mild scoliosis.The hypoplasia of the left lower limb is shown in Figures 1 and 2. _________________________________________   6,7 .Described clinical manifestations include microcephaly, hypertelorism, epicanthic folds, hypoplastic or low set ears, mid-face hypoplasia, hypoplastic distal phalanges, abnormalities of male genitalia, pre and postnatal growth retardation, cleft palate, cardiac and/or renal anomalies and anal atresia/stenosis 8 .This case did not have the major anal, ear or eye malformations [especially the 'cat eye' sign caused by iris coloboma] that are classically associated with this syndrome.The presence of some but not all the described malformations is consistent with the variability of the condition, which in turn reflects the proportion of the trisomic cells in each tissue or organ.
The presence of linear pigmentary anomalies [either hyper or hypopigmentation] along the lines of Blaschko associated with the presence of asymmetry of the body is typical of a mosaic genetic disorder.Such mosaicism could be due to a chromosome disorder 9 or a single gene disorder 10 .Some of the mosaic disorders are clinically distinct and therefore recognizable 11,12 while many are less easily diagnosed due to the nonspecific nature of the findings.
Establishing a genetic diagnosis enables better management including investigations for the associated problems as well as more accurate counselling of the parents regarding the prognosis and recurrence risks.Genetic testing in a child with developmental delay and features suggestive of a mosaic disorder would begin with karyotyping but it is necessary to alert the laboratory for the need to count a larger number of cells on blood karyotype to identify a mosaicism of low frequency 13 .When available, comparative genomic hybridization is the preferred method of diagnosis 14 as its positive yield is higher than with conventional karyotyping.In addition, the use of a buccal cells 15 or fibroblasts 16 for testing is more likely to identify the abnormality.

1
Lady Ridgeway for Hospital for Children, Colombo, Sri Lanka, 2 Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka *Correspondence: mbkcdayasiri@gmail.com(Received on 03 November 2016: Accepted after revision on 23 December 2016) The authors declare that there are no conflicts of interest Personal funding was used for the project.Open Access Article published under the Creative Commons Attribution CC-BY License.She also had hypertelorism, micrognathia and bilateral pre-auricular pits.Her development was globally delayed (gross motor 1 year, fine motor 1 ½ years, speech 1 ½ years, social 2 years).She had central hypertonia with joint hypermobility and bilateral genu recurvatum.Her neck and posterior hairline were normal.