in 1912 , crouzon described a syndrome that consisted of brachycephaly , shallow orbits , and maxillary hypoplasia . since then , craniofacial syndromes have been subcategorized into over a hundred syndromes based on the severity of the craniofacial and associated congenital malformations . crouzon syndrome , along with apert , carpenter , chotzen , and pfeiffer syndromes , is one of the most common genetic disorders associated with a craniofacial syndrome . other facial deformities in crouzon syndrome may include prominent nose , frontal bossing , and ocular proptosis due to shallow orbits with or without hypertelorism , although age - related phenotype modifications have been reported . patients of crouzon syndrome may occasionally present with hydrocephalus , seizures , and mental retardation . the incidence of hydrocephalus in craniosynostosis ranges from 4% to 26% [ 4 , 5 ] . nonetheless , short stature with growth hormone deficiency ( ghd ) and/or iron deficiency anemia ( ida ) have rarely been reported in the literature . here we report a case of crouzon syndrome with hydrocephalus , also presenting with severe short stature due to ghd and ida . an 11 and a half - year - old boy visited our out - patient clinic for frequent dizziness and marked growth retardation . the positive facial features were brachycephaly , hypoplasia maxilla , severe ocular proptosis ( hertel 's exophthalmometry measuring 22 - 23  mm on both eyes ) with hypertelorism , and low - set ears . he had a 3200  gm birth weight and was born to a generally healthy mother via nsd at 40  wks ' gestational age . owing to severe hydrocephalus and cerebellar tonsil herniation ( chiari i malformation ) revealed by magnetic resonance imaging ( mri ) , he had endoscopic third ventriculostomy and six months later , he received frontal advancement and ventricular shunting because of a progressive increase in ventricular size and rising intracranial pressure ( icp ) . his head circumference remained at around the 50th percentile , but he had frequent respiratory tract infections during early childhood . the patient had not been followed up regularly after the age of 6  years until recently . he was 18.5  kg and 111.2  cm , which represented 3 standard deviation ( sd ) in body weight and 5 sd in height of his age . his brother , who is 4 and a half years older , was 182  cm . his parents are grossly normal and the mid - parent height is 168  cm . on admission , his general condition was stable and intelligence quotient ( iq ) around 90 . chromosome analysis was normal in g - banding karyotype ; however , molecular analysis identified a common mutation point of cys278phe in exon iiia of the fibroblast growth factor receptor 2 ( fgfr2 ) gene ( figure 1 ) . his bone age was only 4.55  years according to the greulich and pyle atlas ( figure 2 ) , which was a 6.5 - 7-  year delay . mri revealed obstructive hydrocephalus of both lateral ventricles with an interruption of pituitary stalk , shallow orbits , and chiari i malformation . pituitary height was 5.6  mm in midsagittal t1-weighted spin - echo mri ( figure 3 ) , which was around mean according to tsunoda 's study . a biochemistry profile revealed thyroid hormones and cortisol within normal limits , but blood routine showed microcytic anemia . a growth hormone provocative test revealed a reduced peak growth hormone response of 4.57  uiu / ml in the insulin test and 2.63  uiu / ml in the clonidine test . the concentrations of insulin - like growth factor 1 ( igf - i ) and insulin - like growth factor binding protein 3 ( igf - bp3 ) were also very low ( igf - i < 10.0  ng / ml , igfbp-3 : 1.5  g / ml ) . severe iron deficiency anemia without thalassemia was noted ( hemoglobin : 8.8  g / dl , rbc : 4.18  million / ul , mcv : 68.2  fl ; serum iron : 7  mg / dl , ferritin : 4  ng / ml , uibc : 525  mg / dl ) with regards to the microcytic anemia . iron supplements at a dose of 100  mg / day were subscribed immediately . human growth hormone ( hgh ) subcutaneous replacement at a dose of 0.3  mg / kg / week in seven divided doses was also subscribed , and the growth velocity was 3  cm per year during the first half year . after his hemoglobin and serum iron levels gradually returned to normal , his dizziness disappeared and his growth velocity increased to 5  cm per year under hgh therapy . we reviewed the literature for the incidence of hydrocephalus in crouzon syndrome and the association with ghd , only one case report :  crouzon syndrome with short stature due to partial ghd    was found . however , with the progressive improvement and higher usage of imaging studies , cases of the incidence of hydrocephalus in crouzon syndrome are not uncommon . from proudman 's large study of central nervous system imaging in crouzon syndrome performed in south australia , most of those taken with follow - up computed tomographic scans were nonprogressive , even in cases of severe ventriculomegaly ( hydrocephalus ) . , he suggests that hydrocephalus occurs secondary to the defective formation of the cranium , so it is reasonable that in many cases the hydrocephalus is nonprogressive . most ventriculomegaly in crouzon syndrome is asymptomatic and does not necessitate any treatment , unless there is a clear evidence of significantly raised intracranial pressure . fronto - orbital advancement and shunt system are treatments of choice . in our report case , ghd may have resulted in this patient 's growth retardation , which is not a common finding in crouzon syndrome . there have been a few reports of endocrine disorders in children with shunted hydrocephalus , such as sexual precocity [ 10 , 11 ] or decreased basal levels of gh and igf-1 . increased intracranial pressure has been perceived as a possible cause of pituitary dysfunction . in a series of papers by lppnen et al . [ 1316 ] , the growth pattern of 114 children with shunted hydrocephalus was analyzed . it was characterized by slow linear growth in prepuberty , accelerated physical maturation during puberty , and reduced final height . this has also been shown to be associated with accelerated pubertal development in both boys and girls . furthermore , they studied these patients ' serum growth hormone , plasma igf-1 , and   igfbp-3 concentrations . they concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients . since there was an association with growth hormone , lppnen et al . designed a study performing radiography of the sella turcica , mri of the pituitary gland , and pituitary hormone stimulation tests in a subgroup of this large series ( 54 out of 114 ) to assess pituitary size and functional capacity . the results indicated that children with shunted hydrocephalus had an increased pituitary size on average . about one - third of these patients had signs of reduced gh secretion and a significantly lower pituitary height , which probably contributed to their poor linear growth . increased pituitary size was associated with enhanced gonadotrophin secretion , which may result in early puberty in children with shunted hydrocephalus . another review article about disorders of growth and puberty in children with nontumoral hydrocephalus had similar results . they concluded that central early puberty was the most frequent endocrine disorder in 21 out of 31 patients . in their cases , short stature was frequently due to meningomyelocele and rarely to gh deficiency . in our case , the pituitary height in mri was not smaller than normal for his age , but an interruption of the pituitary stalk was found . his hydrocephalus and chiari i malformation were stationary except for the shallow orbits becoming more prominent . he had severe proptosis but his visual acuity was normal . although chiari i malformation could also cause headache or dizziness , his dizziness might have been caused by severe ida , since the symptoms disappeared after anemia correction . the results of hgh treatment were not satisfactory during the first half year , but became better after ida had been corrected . therefore , besides the compliance and method of hgh injection , other underlying diseases should be considered and treated if the therapeutic effect is not as expected . tubbs et al . reported a study which showed that a small group of children with ghd had small posterior fossa , which was similar to the features of chiari patients . they hypothesized that ghd might lead to chiari i malformation through the underdevelopment of the posterior fossa . in one of their following case studies , by presenting the case of 3 brothers , 2 with ghd and chiari , and one with neither , they provided evidence of this . therefore , it would be interesting to see if hgh therapy leads to the improvement of chiari malformation . although surgery is not necessary in our case so far , we hope to see hgh therapy contributes to improvement of chiari malformation by the annual mri survey . the diagnosis of crouzon syndrome is usually made by the patients ' clinical signs , including acrocephaly , orbital proptosis , midfacial hypoplasia with nose , short upper lip , high narrow palate , narrowly spaced teeth , and prognathism . to date , most patients have been shown to carry mutations of the fgfr2 gene . in   chiang 's mutation analysis of crouzon syndrome in taiwanese patients , three of the 12 patients carried the cys342arg mutation , which is the most frequent mutation found in taiwanese patients . molecular analysis of the fgfr2 gene can help to confirm and classify the diagnosis of craniosynostosis syndrome .
crouzon syndrome is one of the most common craniofacial syndromes and is inherited as autosomal dominant with variable expression . 
 we report an 11 and a half - year - old boy with crouzon syndrome with severe growth retardation . 
 he had hydrocephalus since infancy and recently suffered from frequent dizziness . 
 his bone age was only 5 years according to the greulich and pyle atlas . 
 magnetic resonance imaging showed shallow orbits , obstructive hydrocephalus , and cerebellar tonsil herniation . 
 growth hormone provocative tests revealed a reduced peak growth hormone response in both insulin and clonidine tests . 
 severe iron deficiency anemia was noted at the same time . 
 molecular analysis identified a common mutation point of cys278phe for crouzon syndrome in exon iiia of the fibroblast growth factor receptor 2 ( fgfr2 ) gene . 
 since growth retardation is not a common feature of crouzon syndrome , we reviewed the literature for the incidence of hydrocephalus in crouzon syndrome and the association with growth hormone deficiency .