chromosomal heteromorphisms are interindividual variation of chromosomes without phenotypic consequences and are detected most frequently in 1q12 , 9q12 , 16q11.2 , yq12 and in the short arms of acrocentric chromosomes ( 13 , 14 , 15 , 21 and 22 ) . in some cases , the enlarged acrocentric p arms of p arm can mask a cryptic translocation and therefore a partial trisomy . here , we report a moroccan 1-year - old girl addressed for suspicion of trisomy 21 having an extremely enlarged p arm in one of her chromosomes 22 .
her length was 78 cm ( 25 centile ) , weight 10 kg ( 25 centile ) and head circumference 46 cm ( 50 centile ) .
she had no psychomotor delay but she had mild dysmorphism including round face , up slanting palpebral fissures , epicanthus , small nose , low - set ears and high arched palate [ figure 1 ] ; echocardiography was normal .
the index propositus having a down - syndrome like facies cytogenetics studies were performed on metaphase chromosome preparations obtained from phytohemagglutinin stimulated lymphocyte cultures according to standard procedures .
chromosome analysis was carried out applying rhg banding at a 400 band level as previously reported and according to the international system for human cytogenetic : nomenclature iscn 2009 . nor staining was realized using standard protocols , as well .
fluorescence in situ hybridization ( fish ) was carried out following respectively manufacturer 's instructions and/or as previously reported .
30 - 19002 ) encompassing two genes dscr4 and dscr8 with 3 markers d21s259 , d21s341 , d21s342 in 21q22.13-q22.2 ( down - syndrome critical region ) and a whole chromosome paint ( wcp ) 21 probe ( cytocell cat n lpp21r ) .
besides a microdissection derived home brew probe specific for all acrocentric short arms and denominated as midi54 and a the centromere - specific probe d14z1/d22z1 , which at the same time hybridizes to centromeres of chromosome 14 and 22 ( kreatech ) .
cytogenetics studies were performed on metaphase chromosome preparations obtained from phytohemagglutinin stimulated lymphocyte cultures according to standard procedures .
chromosome analysis was carried out applying rhg banding at a 400 band level as previously reported and according to the international system for human cytogenetic : nomenclature iscn 2009 . nor staining was realized using standard protocols , as well .
fluorescence in situ hybridization ( fish ) was carried out following respectively manufacturer 's instructions and/or as previously reported .
30 - 19002 ) encompassing two genes dscr4 and dscr8 with 3 markers d21s259 , d21s341 , d21s342 in 21q22.13-q22.2 ( down - syndrome critical region ) and a whole chromosome paint ( wcp ) 21 probe ( cytocell cat n lpp21r ) .
besides a microdissection derived home brew probe specific for all acrocentric short arms and denominated as midi54 and a the centromere - specific probe d14z1/d22z1 , which at the same time hybridizes to centromeres of chromosome 14 and 22 ( kreatech ) .
cytogenetics studies were performed on metaphase chromosome preparations obtained from phytohemagglutinin stimulated lymphocyte cultures according to standard procedures .
chromosome analysis was carried out applying rhg banding at a 400 band level as previously reported and according to the international system for human cytogenetic : nomenclature iscn 2009 . nor staining was realized using standard protocols , as well .
fluorescence in situ hybridization ( fish ) was carried out following respectively manufacturer 's instructions and/or as previously reported .
30 - 19002 ) encompassing two genes dscr4 and dscr8 with 3 markers d21s259 , d21s341 , d21s342 in 21q22.13-q22.2 ( down - syndrome critical region ) and a whole chromosome paint ( wcp ) 21 probe ( cytocell cat n lpp21r ) .
besides a microdissection derived home brew probe specific for all acrocentric short arms and denominated as midi54 and a the centromere - specific probe d14z1/d22z1 , which at the same time hybridizes to centromeres of chromosome 14 and 22 ( kreatech ) .
r banding analysis of the chromosomes from peripheral blood of the propositus revealed a normal karyotype apart from an enlarged short arm for one chromosome 22 inherited from the mother [ figure 2 ] .
thus , the karyotype was reported as 46 , xx , der ( 22 ) add ( 22)(p13 ) mat . applying the nor staining results were quite variable and overall non - informative ( data not shown ) .
a partial r banding karyotype of the propositus ( a ) and her mother ( b ) showing enlarged short arm of one chromosome 22 a probe lsi 21 of the critical region for the down - syndrome critical region and a wcp 21 probe excluded the presence of a cryptic trisomy 21 [ figure 3 ] .
fish using a probe for all acrocentric short arms characterized the additional material on the der ( 22 ) as heterochromatin derived from an acrocentric short arm [ figure 4 ] .
therefore , according to cytogenetic and molecular cytogenetic characterization the karyotype was 46 , xx,22ph+++ mat .
metaphases hybridized with down - syndrome critical region probe lsi 21 ( a ) and whole chromosome paint ( wcp ) for chromosome 21 ( b ) . ( a )
( b ) wcp 22 revealed a complete hybridization of the two long arms of chromosome 21 .
neither der 22 nor other chromosomes revealed signal for any of the two probes the short arm of the chromosome 22p++ on the right was completely stained by a probe specific for the acrocentric short arm ( midi54 ) indicating its heterochromatic nature
cytogenetic and fish investigation of the propositus excluded ( cryptic ) trisomy 21 as already reported in down - syndrome like syndrome phenotypes .
instead of clarifying the genetic reason of the clinical problems in this specific case unexpectedly a familial 22ph+++ was detected and further characterized .
uninformative results as seen after nor silver staining was reported by some authors as well , previously .
thus , nowadays fish analysis is more straightforward for the characterization of heteromorphisms in general and acrocentric short arm variants in special .
this kind of molecular cytogenetic analysis also enables to distinguish heteromorphic variants from partial trisomies due to cryptic translocations .
most likely heterochromatin loss or gain are not causative for acquired or inherited disorders , even though such relations still are discussed . to the best of our knowledge ,
this special here reported kind of chromosome 22 short arm enlargement , leading ro ~1.5 larger size than the normal  long arm 
fish should always be used to resolve similar situations involving cytogenetic aberrations within the short arms of acrocentric chromosomes .
further follow - up of the propositus may allow us to have more clinical information and making some correlations between this heteromorphism and/or other genetic changes below the cytogenetic resolution and the phenotype of the patient .
 chromosomal heteromorphisms are described as interindividual variation of chromosomes without phenotypic consequence . 
 chromosomal polymorphisms detected include most regions of heterochromatin of chromosomes 1 , 9 , 16 and y and the short arms of all acrocentric chromosomes . here 
 , we report a girl with down - syndrome such as facies and tremendously enlarged short arm of a chromosome 22 . 
 fluorescence in situ hybridization ( fish ) with a probe specific for all acrocentric short arms revealed that the enlargement p arms of the chromosome 22 in question contained exclusively heterochromatic material derived from an acrocentric short arm . 
 parental studies identified a maternal origin of this heteromorphism . 
 cryptic trisomy 21 of the down - syndrome critical region was excluded by a corresponding fish - probe . here 
 , we report , to the best of our knowledge , largest ever seen chromosome 22 short arm , being ~1.5 larger than the normal long arm . 