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Paper text:
epidermal nevus with hemifacial hypertrophy can occur in schimmelpenning syndrome , phakomatoses pigmentokeratotica , proteus syndrome and type 2 segmental cowden disease .
the epidermal nevus syndromes are a group of congenital syndromes comprising epidermal nevi in conjunction with central nervous system ( cns ) , ocular , musculoskeletal , and other organ anomalies .
most epidermal nevi are noticed at birth or develop during the first year of life .
reports of associated hemi hypertrophy of the face are multiple and almost always noticed at birth .
we herewith report a patient having an epidermal nevus at 25 years of age with onset of gradually progressing hemihypertrophy of face associated with overlying hypertrichosis .
genetic analysis done from the skin did not reveal fibrobalst growth factor receptor 3 ( fgfr3 ) mutations .
a 26-year - old man reported to skin outpatient department with dark warty growth on left side of cheek for past 6 years .
he noticed gradual disproportionate enlargement of the left side of face after the onset of the growth .
he had no history of seizures , headaches or any other cns events . on examination
, there were linear hyperpigmented verrucous papules with overlying hypertrichosis on left side of cheek extending on to the neck [ figure 1a ] .
the left side of the face looked larger than the right [ figure 1b ] .
x - ray skull was suggestive of mandible condylar hyperplasia . however , orthopantogram revealed slight widening of ramus ; no other bony abnormality was observed .
computed axial tomography of the cranium and brain showed thickening of the frontal bone on the left side [ figure 2 ] .
skin biopsy of the representative skin lesion ( face ) showed hyperkeratosis with papillomatosis [ figure 3 ] .
genetic analysis was done from the skin in the area affected by the nevus . on genetic analysis of skin samples taken from the nevus ,
only wild type alleles were revealed for the hotspot loci on fgfr3 and p110 subunit of phosphatidyl inositol-3 - kinase ( pik3ca ) .
( a ) verrucous epidermal nevus with overlying hypertrichosis on left side of face and neck , ( b)- hemihypertrophy of left side of face and scalp ct scan showing thickening of frontal bone on left side section of skin biopsy showing hyperkeratosis , acanthosis , and papillomatosis .
keratinocytic nevi and sebaceous nevi can be associated with epidermal nevus syndromes ( enss ) .
the epidermal nevus syndrome refers to a sporadic neurocutaneous disorder characterized by epidermal nevi , ophthalmological and neurological manifestations .
happle has described multiple phenotypes associated with cutaneous mosaicism and made a strong case for avoiding umbrella terms like epidermal nevus syndrome and organoid nevus syndrome when describing a specific ens .
the well - defined syndromes are schimmelpenning syndrome , phakomatoses pigmentokeratotica , nevus comedonicus syndrome , angora hair nevus syndrome , becker 's nevus syndrome , type 2 segmental cowden disease , fgfr3 segmental nevus syndrome , and child ( congenital hemidysplasia with icthyosiform erythroderma and limb defects ) syndrome .
of these , schimmelpenning syndrome , phakomatoses pigmentokeratotica , proteus syndrome , and type 2 segmental cowden disease may be associated with hemi hypertrophy of face or limbs . however
patients with hemihypertrophy of face usually are reported to have cortical defects like hemimegalencephaly , focal cortical dysplasia , and neuronal migration defects like pachygyria and polymicrogyria heterotopias in the affected hemisphere .
our patient had relatively late onset of epidermal nevus associated with left - sided progressive hemihypertrophy of the face and hypertrichosis .
hypertrichosis confined to the area of epidermal nevus is described in angora hair nevus syndrome and in a case of epidermal nevus with bony abnormalities described by gobello et al .
gobello et al . described a 16-year - old boy with non - epidermolytic epidermal nevus , hypertrichosis and follicular hyperkeratosis in addition to hemihypoplasia of limbs , brachydactyly , clinodactyly , and onychodystrophy .
genetic analysis done from the affected skin in this case did not reveal mutations in fgfr3 . in our patient too , only wild type alleles for fgfr3 were seen in affected skin .
our patient had hypertrichosis overlying an epidermal nevus with hemihypertrophy of face . while the features do not exactly match those described by gobello et al .
genetic analysis done from lesional skin showed only wild - type alleles of both fgfr3 and pik3ca genes .
somatic mosaicism for fgfr3 mutations involving skin and other organ systems have been described in patients .
if the mutation involves the gonads , such patients are said to be at risk for thanatophoric dysplasia . in many other patients with epidermal nevi , somatic mutations resulting in mosaicism confined to keratinocytes of the affected area have been demonstrated in the fgfr3 gene , specifically at the r248c hotspot , and in the pik3ca gene .
child syndrome is caused by nsdhl ( nad ( p ) h steroid dehydrogenase - like ) gene mutations ; type 2 cowden disease by pten ( phosphatase and tensin homolog ) mutations .
we report this unique case of late onset epidermal nevus with hypertrichosis and hemihypertrophy as it does not belong to any of the classical epidermal syndromes .
a possible association to  gobello syndrome  can not be confirmed until more molecular diagnostic techniques are developed and employed .
hemifacial hypertrophy and hypertrichosis can occur in association with epidermal nevus in the absence of fgfr3 mutations .
this does not fit into any of the known ens and could be a new entity .
epidermal nevus syndromes are rare conditions , characterized by different types of keratinocytic or organoid epidermal nevi in association with ocular , neurological , and skeletal manifestations 
 . we present a case of late onset epidermal nevus with hypertrichosis and hemihypertrophy of face . 
 genetic analysis did not reveal presence of fgfr3 or pik3ca mutations . 
 the patient has features that can not be categorized into the present well - known syndromes .