partial chromosome 7p duplication has been reported in at least 60 individuals and generally associated with unbalanced chromosome translocations.1 
 2 
 3 however , chromosome 7p duplication can arise de novo , possibly because of nonallelic homologous recombination.1 the short arm of chromosome 7p includes 17 bands and sub - bands at high - resolution 850-band level . the chromosome 7p22 band consists of three sub - bands and is often implicated in the 7p duplication syndrome . papadopoulou et al2 provided a review of the 7p duplication syndrome and reported that the most common phenotypic findings were intellectual disability , hypotonia , abnormal palmar creases , skeletal abnormalities ( broad halluces / thumbs / digits , foot and thorax malformations , joint contractures , or dislocations ) , cardiovascular abnormalities , and craniofacial dysmorphism ( large anterior fontanel , ocular hypertelorism , low - set ears , high - arched , and/or cleft palate ) . vulto - van silfhout et al4 reported the smallest known duplication in the chromosome 7p22.3 sub - band ( 380  kb in size ) in a patient presenting with only an autism spectrum disorder ( asperger syndrome ) and a broad nasal bridge . later , preiksaitiene et al3 reported the smallest 7p duplication ( 1 mb duplication ) at 7p22.l with features consistent with the recognized phenotype seen in this duplication syndrome . we report a patient with a 629  kb duplication at 7p22.2 ( position 2,878,6773,507,572 , national center for biotechnology information [ ncbi ] build 36 ) , the sub - band located between 7p22.1 and 7p22.3 . our patient presented with features of the 7p duplication syndrome , yet importantly , our patient shares phenotypic features in common with patients described with the 7p duplication of larger size . this is also the first patient reported with a duplication at chromosome 7p22.2 sub - band ; allowing for better delineation of the clinical presentation of this chromosomal duplication syndrome and further determination of the chromosomal critical region . our patient is a 14-year - old hispanic male who presented for genetic evaluation for developmental delay and dysmorphic features . the patient was the product of an unremarkable full - term pregnancy weighing 3.010  g ( 17th centile ) . developmental milestones were delayed ; he sat up at 12 months , walked at 2 years , spoke his first word at 2 years , and used two - word sentences at 3 years of age . our patient had polyethylene ear tubes placed on three separate occasions between the age of 2.5 and 5 years . he began speaking after the first set of ear tubes . at the age of 8 years , he was administered the wechsler intelligence scale for children with the following derived scores : verbal intelligence quotient 57 , performance intelligence quotient 58 , full - scale intelligence quotient 53 , verbal comprehension 61 , and perceptual organization 56 . he has had an individualized education plan in place since entrance in the school system requiring special education services . health issues include asthma , which is well - controlled , and corrective glasses for myopia . at the age of 11 years , he had bilateral achilles tendon release surgery to correct a toe - walking gait , and later at the age of 12 years , additional corrective surgery of the left foot was undertaken because of the malposition interfering with walking . our patient had an extensive genetic work up in the past including a karyotype to explore the possibility of down syndrome performed at the age of 12 years , which showed a normal male karyotype . he had fragile - x dna testing performed at the age of 13 years , which was also normal . he had two separate microarrays , one at the age of 10 years and the other at the age of 13 years . at the age of 10 years , a single nucleotide polymorphism ( snp ) microarray analysis was performed using the affymetrix 6.0 snp array with 1.8 million probes consisting of 900,000 snp probes and 900,000 copy number probes with a median spacing of 0.7  kb ( labcorp , research triangle park , north carolina , united states ) . data were analyzed using the affymetrix genotyping console browser v. 3.01 ( affymetrix , santa clara , california , united states ) and genomic imbalances reported using the university of california santa cruz ( ucsc ) human genome build 18 ( ncbi build 36 ; 2006 ) . this array showed a 629  kb duplication involving the chromosome 7p22.2 band ( hg18 coordinates chr7:28786773507572 ) . maternal studies were performed using a custom - designed familial follow - up protocol with region - specific fluorescence in situ hybridization bacterial artificial chromosome probe(s ) ( rp11659f18    2 ) ( labcorp , research triangle park ) showing a normal copy number and hybridization signals in all nuclei . the father was unavailable for testing . at the age of 13 years , an affymetrix cytoscan ( affymetrix , santa clara , california , united states ) hd microarray was performed containing 2.6 million probes with at least one probe per 3 kb . genomic imbalances were reported using the ucsc human genome build 1a ( ncbi build 37 ; 2009 ) and the array showed a 634  kb duplication involving the same chromosome 7p22.2 band ( hg19 coordinates chr7:29073753541046 ) as found earlier and included two known genes ( caspase recruitment domain family , member 11 [ card11 ] and sidekick cell adhesion molecule 1 [ sdk1 ] ) . during the physical examination at the age of 14 years , he was a pleasant hispanic male with dysmorphic features including prominent appearing supraorbital ridges , mild synophrys , slightly upslanting palpebral fissures , relatively small and irregularly - shaped pupils , malar hypoplasia , low - set protruding ears with prominent lobes , posterior creases and pit - like depressions located bilaterally , hypoplastic alae nasi with depressed nasal tip and a narrow appearing nose , a high - arched palate , alopecia areata ( 2    3 cm ) located in the left occipital region , a caf au lait spot measuring 0.5 cm in size in the center of the abdomen , malalignment of feet , and proportionate short stature . his reflexes were normal of both the lower and upper extremities along with normal coordination . no edema , joint laxity or tenderness , leg length asymmetry , other cutaneous lesions , abdominal masses / tenderness , or respiratory distress , were noted . his height was 146.8 cm ( < 3rd centile ) , weight 63.86  kg ( 80th centile ) , head circumference 54 cm ( 50th centile ) , inner canthal distance 2.9 cm ( 30th centile ) , outer canthal distance 7.8 cm ( 3rd centile ) , interpupillary distance 5.2 cm ( 15th centile ) , palpebral fissure 2.5 cm ( 11th centile ) , ear length 5.7 cm ( 35th centile ) , total hand length 16.3 cm ( 14th centile ) , and middle finger length 6.3 cm ( < 3rd centile ) ( fig . the family history was remarkable for four paternal half - siblings who were reported to have learning disabilities . one paternal half - brother reportedly wears hearing aids and has a similar physical appearance to our patient . no further family history or information about the father was available , although our proband apparently had several physical features in common with his father . ( a  g ) standing and facial , frontal , and profile views with images of back of head and ears and feet from our patient having a 7p22.2 microduplication found by microarray analysis . duplications of chromosome 7p22 are known to cause a spectrum of phenotypic features as seen in our 14-year - old male patient with a full - scale intelligence quotient of 53 , developmental delays , and dysmorphic features . to our knowledge , the patient 's duplication at 7p22.2 is the smallest found to date while still containing the phenotypic features seen in the 7p duplication syndrome . we examined five cases reported in the literature and web - based resources of genomic variation data ( e.g. , decipher ) . three cases ( cases c , d , and e ) had overlapping genomic regions in common with our patient ( case f ; see fig . 2).5 the 7p22 duplications in the five previous reported cases ranged from 390 to 980 kb . three of the cases found in the decipher database5 had genomic coordinates located at 3.14 to 3.30 mb from the p terminus region , approximately 160  kb in length , which overlaps with our patient 's microduplication . this overlapped region includes the card11 , sdk1 , and guanine nucleotide - binding protein ( g protein )  12 ( gna12 ) genes . location of interstitial chromosome 7p22 duplication for our patient and others reported in the literature and genomic databases . deletions of previously reported subjects are indicated as ; ( a ) interstitial gain in band p22.3 of chromosome 7 estimated at a minimal size of 380  kb to a maximal size of 450  kb in a patient with asperger syndrome,4 ( b ) 980  kb duplication of 7p22.1 region in a patient with features consistent with 7p22 duplication syndrome ( position 5,337,0726,316,915 , ncbi build 36),3 ( c ) decipher case 292740 , 389  kb gain at 7p22.2 ( position 3,142,0743,531,219 , ncbi build 36 ) involving only the sdk1 gene in a patient with cognitive impairment,5 ( d ) decipher case 274816 , 450  kb gain at 7p22.2 ( position 2,845,3723,298,538 , ncbi build 36 ) involving the card11 and gna12 genes in a patient with generalized tonic seizures,5 ( e ) decipher case 282143 , 763  kb gain at 7p22.2 ( position 2,817,8743,580,692 , ncbi build 36 ) involving the sdk1 , card11 , and gna12 genes in a patient with a second copy number variant on chromosome 6 and having a heart abnormality , cerebellar vermis hypoplasia , and renal hypoplasia / aplasia,5 and ( f ) our patient with a 629  kb duplication at 7p22.2 ( position 2,878,6773,507,572 , ncbi build 36 ) . the smallest region of overlap among the four subjects with the 7p22.2 duplication occurred between the genomic coordinates 3.14 and 3.30 mb from the p terminus . our patient 's deletion included two genes , caspase recruitment domain family , member 11 ( card11 ) and sidekick cell adhesion molecule 1 ( sdk1 ) . the card11 gene is associated with autosomal dominant persistent polyclonal b cell lymphocytosis ( omim # 606445 ) and autosomal recessive immunodeficiency type 11 ( omim # 615206 ) . the sdk1 gene may be associated with determinants of lamina - specific synaptic connectivity specifically playing a role in neurodevelopment and function.6 
  interstitial duplications of the 7p22.1 band have been reported previously1 
 3 with characteristic features of the 7p duplication syndrome including macrocephaly , open anterior fontanel , frontal bossing with a flat , broad nasal bridge , ocular hypertelorism , anteverted nares , microretrognathia , high narrow palate , microstomia , low - set posteriorly rotated ears with preauricular pit , speech delay , and skeletal anomalies . our patient 's cytogenetic duplication does not overlap with previously identified microduplications of 7p22.1 as his duplication is located more telomeric at the 7p22.2 sub - band , although he had several features in common with the partial 7p duplication syndrome including prominent appearing supraorbital ridges , slightly upslanting palpebral fissures , malar hypoplasia , low - set protruding ears with posterior creases and depressions with prominent lobes , hypoplastic alae nasi , depressed nasal tip with a narrow appearing nose , a high - arched palate , speech delay , and intellectual disability . in conclusion , this clinical case is of interest as the first report of a microduplication of the 7p22.2 sub - band with dysmorphic features similar to those reported in the partial 7p duplication syndrome ; indicating that the 7p22.2 sub - band may play a role in this phenotype . further research is needed to determine the role of the 7p22.2 microduplication in causing the 7p duplication syndrome . reporting further cases with microduplications of the 7p region are encouraged to better characterize the dosage - sensitive candidate gene(s ) resulting in features seen in the partial 7p duplication syndrome . the smallest region of overlap in the 7p22.2 band was positioned at genomic coordinates located at 3.14 to 3.30 mb from the chromosome 7p terminus in our patient ( case f ) and for cases c , d , and e from the decipher database as illustrated in fig .
we report a 14-year - old hispanic male with a microduplication of the chromosome 7p22.2 band detected through microarray analysis . 
 he had a history of developmental delay and mild intellectual disability , asthma , myopia , proportionate short stature , dysmorphic features , and achilles tendon release . 
 this appears to be the first report of a patient with a microduplication of only the chromosome 7p22.2 band and is now the smallest reported duplication to date to include features in common with the chromosome 7p22 duplication syndrome .