x - linked dominant chondrodysplasia punctata ( cdpx2 , omim 302960 ) is an inheritable systemic disease and is characterized by skeletal , ophthalmologic , and cutaneous manifestations . in the late seventies , rudolph happle reported a female and brilliantly recognized a group of published patients with chondrodysplasia punctata whose mosaic phenotype and sex rate corresponded with an x - linked dominant pattern of inheritance . in 1999 , the gene emopamil binding protein ( ebp ) was identified and associated with cdpx2 , so called conradi - hnermann - happle syndrome .
the ebp gene is located on the short arm of the x chromosome ( xp11.22-p11.23 ) and spans 7 kb of genomic dna , containing five exons coding a mature transcript of 1 kb which is ubiquitously expressed .
this protein consists of 230 amino acids and four transmembrane domains , it has a molecular weight of 27 kda and it is implicated in cholesterol biosynthesis .
cutaneous lesions in cdpx2 usually start as erythematous scaly plaques following the lines of blaschko that fade over time , and some patients may be born with congenital erythroderma .
while cdpx2 may exhibit variable phenotypes , psoriasiform skin lesions are exceptional and histopathologic investigations of psoriasiform skin lesions show epidermal hyperproliferation in addition to ichthyotic retention hyperkeratosis . in this report , a case of a 12-year - old girl diagnosed with x - linked dominant chondrodysplasia punctata with a psoriasiform phenotype is reported with genetical confirmation .
we discuss here a rare clinical presentation which helps in better depict this rare genodermatosis and on the lack of correlation between phenotype and genotype in this disease .
a 12-year - old girl , who had been born with congenital erythroderma , had a 4-month history of linear and whorled inflammatory cutaneous lesions on her trunk , leg , and arms .
extensively distributed thickly adherent scaling had been developed at the age of one , and continued since then .
the patient had been born at term following a normal pregnancy and delivery and family history was unremarkable .
she displayed growth retardation , bilateral conductive hearing , and unilateral congenital cataract in her right eye .
she exhibited short stature with asymmetric shortening of her limbs , being her right arm shorter than her left .
dysmorphic facial features with frontal bossing , flat nasal bridge , and a depressed tip of the nose were observed .
dermatological examination revealed brown streaky hyperkeratotic plaques with thickly adherent scaling located along blaschko 's lines .
also , erythematous scaling and guttate lesions were observed on her trunk , arms , and legs .
there were patchy areas of scarring alopecia on frontal and temporal regions of the scalp and lateral regions of eyebrows .
dorsal and lumbosacral magnetic resonance imaging showed scoliosis deformity , height losses of the t8 vertebrae left half and l3 , l4 vertebral the right halves ( tethered cord ) .
clinical features of the patient with conradi  hnermann  happle syndrome ( x - linked dominant chondrodysplasia punctata ) genomic dna of the patient was extracted from peripheral blood leukocytes via a conventional phenol - chloroform method .
exons 1 - 5 and the intronic splicing regions from the ebp gene were amplified by polymerase chain reaction ( pcr ) as previously described .
the reaction was conducted in a 2720 thermal cycler ( applied biosystems , foster city , ca , u.s.a . ) .
automatic sequencing was performed with the abi prism 310 genetic analyzer ( applied biosystems ) .
we identified a previously reported ebp mutation , c. 440 g > a ( p.r147h ) in the patient , but not in her parents [ figure 2 ] . according to the clinical and laboratory findings
, the diagnosis of conradi - hnermann - happle syndrome was established . a skin biopsy of one of the guttate , erythematous , and scaling plaques revealed retention hyperkeratosis , parakeratosis , acanthosis with regular elongation of rete ridges , capillary proliferation , and mononuclear cell infiltration in papillary dermis , being this consistent with a psoriasiform pattern .
the pedigree and dna sequencing showed a heterozygous mutation c. 440 g > a resulting in p.r147h in ebp gene
in conradi - hnermann - happle syndrome , cutaneous findings are remarkable and characterized by hyperkeratotic lesions on an erythematous background following the blaschko 's lines .
bruch et al . described a unique adult patient presenting both with ichthyotic and pustular psoriasiform lesions together .
later , in a large spanish series , a patient with ichthyosis in a psoriasiform pattern was reported with the genetic analysis showed c. 187c > t ( p.arg63x ) de novo mutation .
we here present an exceptional case of cdpx2 with psoriasiform and ichthyotic skin lesions together in an adolescent , the first case from tunisia .
histopathological features of guttate , erythematous , and scaling plaques followed a psoriasiform pattern . in 1999 , the gene ebp was identified and associated with the conradi - hnermann - happle syndrome ( xp11.22-p11.23 ) . to date , about 70 different mutations in the ebp gene have been described related with this disease .
we found a c.(440 g > a ) missense de novo mutation in the ebp gene ( p.arg147his ) , placed in the second endoplasmic reticulum domain ( er2 ) of the protein .
the unique case of cdpx2 with a similar phenotype to ours displayed a c.(187c > t ) , p.arg63x nonsense mutation , which had also been described in two patients with typical skin phenotype of cdpx2 .
the c. 440 g seems to be a nucleotide with particularly high mutational susceptibility within the ebp gene , a hot spot .
on the other hand , the clinical phenotype associated with this mutation has been variable , which subscribes the lack of correlation between genotype and phenotype in this disease .
although the relationship between the various genotypes and phenotypes in conradi - hnermann - happle syndrome has not been fully elucidated , detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling .
our case expands the clinical phenotypic variation in cdpx2 and further demonstrates the lack of correlation between genotype and phenotype in this disease .
unique additional clinical manifestations like plaque - type psoriasis may present with different mutations . conradi - hunermann - happle may represent extensive plaque - type psoriasis in adolescent patients .
 conradi - hnermann - happle syndrome ( cdpx2 , omim 302960 ) is an inherited x - linked dominant variant of chondrodysplasia punctata which primarily affects the skin , bones , and eyes . 
 cdpx2 patients display skin defects , including ichthyotic lesions , follicular atrophoderma , cicatricial alopecia , and less frequently ichthyosiform erythroderma , cataracts , and skeletal abnormalities consisting of short stature , asymmetric shortening of the limbs , epiphyseal stippling , and craniofacial defects . 
 cdpx2 results from mutations in emopamil binding protein ( ebp ) gene . 
 the aim of our study is to identify ebp mutation in a unique case of conradi - hnermann - happle syndrome with rare psoriasiform lesions . 