sotos syndrome is a dysmorphic syndrome characterized by early overgrowth , developmental delay , advanced bone age and characteristic craniofacial appearance .
sotos syndrome results from mutation involving the nuclear receptor set - domain - containing protein ( nsd1 ) gene , located on chromosome 5q .
the mutational mechanism can be a point mutation in the nsd1 gene or a microdeletion that includes nsd1 .
fluorescence in situ hybridization ( fish ) did not detect microdeletion of 5q35 in this patient .
nsd1 gene mutations are also found in weaver syndrome where camptodactyly is a common feature .
this report describes camptodactyly for the first time in a girl with sotos syndrome and provides further evidence that sotos and weaver syndrome are allelic disorders .
we describe a two and half years old girl born of non - consanguineous tamilian parents .
milestones were delayed with head holding at 6 months , walking at 2 years and delayed speech .
family history was unremarkable . at two and a half years she weighed 15 kg ,
height was 97 cm and head circumference was 52.5 cm ( all above 90 centile ) .
she had a high forehead with frontal bossing , dolichocephaly , large ears , pre - auricular pits , down - slanting palpebral fissures , high arched palate , pointed chin and pectus carinatum [ figure 1 ] .
she had three caf au lait spots distributed on the chest and trunk , large hands and camptodactyly of the left hand [ figure 2 ] .
fish studies carried out using probe rp11 - 265k23 did not reveal a microdeletion of the 5q35 region .
face showing the facial features of sotos syndrome left hand showing camptodactly a clinical diagnosis of sotos syndrome was made based on the criteria comprising of rapid early growth , advanced bone age , developmental delay and characteristic facial appearance .
camptodactyly in sotos syndrome has not been previously described in literature to the best of our knowledge .
a high frequency of congenital heart defects has been reported in patients with intragenic mutations of the nsd1 gene and phenotypic overlap with other overgrowth syndromes , in particular with weaver syndrome is seen . though this sotos patient is likely to have a point mutation of the nsd1 gene , this could not be confirmed due to lack of facilities .
sotos syndrome was first recognized as a distinct clinical syndrome in new england in 1964 .
the diagnosis is based on the clinical criteria of rapid early growth ( pre and post natal ) , advanced bone age , developmental delay and characteristic facial appearance .
growth is rapid in the first years of life but final height may not be excessive . intellectually , the iq ranges from 21 to 103 with a mean of 74 and almost half of affected children achieve normal schooling .
behavioral issues are common and are one of the key areas that can influence the outcome .
hypotonia is usually present from birth and although this improves during childhood , subtle evidence may remain even in adults .
congenital heart disease is not very common in this condition and overall incidence of cardiac defects is approximately 8% .
an association of sotos syndrome with tumor development was documented over 30 years ago and has been a point of debate ever since .
gorlin et al . estimated a risk of 3.9% of benign or malignant tumors in sotos syndrome .
handicaps in sotos syndrome are fewer than previously believed and tend to improve with age . in patients with sotos syndrome harboring a chromosomal translocation kurotaki et al
. isolated the nuclear receptor set - domain - containing protein ( nsd1 ) gene from the 5q35 breakpoint .
added noted a large difference between japanese and non - japanese patients in the frequency of microdeletions , which occurred in 49 ( 52% ) of the 95 japanese but in only 1 ( 6% ) of the 17 non - japanese .
there was a strong correlation between presence of an nsd1 alteration and clinical phenotype , in that 28 of 37 ( 76% ) patients with typical sotos or sotos - like phenotype had nsd1 mutations or deletions .
studied nsd1 gene in a series of typical sotos patients ( 23/39 ) , sotos - like patients ( lacking one major criteria , 10/39 ) and weaver patients ( 6/39 ) .
they conclude that nsd1 mutations account for most cases of sotos syndrome and a significant number of weaver syndrome cases . comparing the clinical phenotype of children carrying either a deletion or a mutation , rio et al . failed to detect distinctive features except for the severity of mental retardation .
they reported , 4/6 children carrying a nsd1 deletion were extremely severely mentally retarded with no language at all , major delay in motor milestones and autistic features .
by contrast , in patients carrying nsd1 mutations , mental retardation was usually mild to moderate with verbal skills being more affected .
the major differential diagnoses for sotos syndrome are other conditions with overgrowth including beckwith - weidemann , weaver , nevo and simpson golabi behmel syndromes .
. however nsd1 gene mutations have been found in beckwith - weidemann syndrome , weaver syndrome and the 11p15 abnormalities seen in beckwith - wiedemann syndrome have been found in some cases of sotos syndrome . camptodactly has not been previously described in literature to the best of our knowledge with sotos syndrome but is seen in weaver syndrome where nsd1 mutations have been described .
these could be due to , allelic heterogeneity , effect of other modifying genes ethnic background and nutritional status adding to the overall expression of a syndrome .
microdeletions of chromosome 5 were not detected in our case suggesting a likely point mutation in the nsd1 gene and further evidence of that weaver and sotos syndrome are allelic .
further delineation of the phenotype with molecular studies will provide correct genotype - phenotype correlations .
 we describe a girl with sotos syndrome presenting at two and a half years age with developmental delay . 
 she has camptodactyly which has not previously been reported in sotos syndrome but is a common finding in weaver syndrome . 
 both these conditions have been reported to have nsd1 gene mutations . 
 this report is consistent with the conditions being allelic . 