IP is a rare genodermatosis, inherited in an X-linked dominant fashion. It is lethal in males, resulting in an observed female-male ratio of 37:14
. IP has been observed, albeit rarely, in males with somatic mosaicism, Klinefelter syndrome (47, XXY), and hypomorphic alleles6
. IP is caused by mutations in the NEMO/IKKγ gene located on Xq287
. The most common NEMO abnormality in IP is a deletion of exons 4 through 10, which occurs in 70~80% of IP patients8,9
. The remaining patients have other alterations in NEMO, including small duplications, substitutions, and deletions.
IP can affect ectoderm-derived structures, including the skin, teeth, eyes, nervous tissue, hair, and nails3,4
and may be seen in association with abnormalities of the musculoskeletal system and heart3,4
. In a study of 653 IP patients, 521 (79.8%) had systemic symptoms and signs4
Three or four stages of IP have been reported in the skin. In the vesicular stage (Stage I), erythema, vesicles, and pustules appear in a linear arrangement within the first 2 weeks of life; the extremities and trunk are the most affected areas. In the verrucous stage (Stage II), hyperkeratotic verrucous papules and plaques appear at about 2 months of age. The hyperpigmented stage (Stage III), which is characterized by irregularly whorled hyperpigmented patches, follows as the verrucous lesions resolve. In some patients, an atrophic stage (Stage IV) occurs. Cutaneous lesions in all stages tend to follow Blaschko's lines10
. Histopathologically, stage I is characterized by eosinophilic spongiosis, intraepidermal vesicles, and dermal infiltration, and the number of eosinophils may increase in the peripheral blood. Stage II is characterized by dyskeratotic keratinocytes, hyperkeratosis, acanthosis, and papillomatosis, and stage III is characterized by vacuolar changes of the basal layer and several dermal melanophages. In stage IV, skin appendages may be absent, with mild epidermal atrophy and decreased, normal, or small melanocytes.
Scarring alopecia has been observed in 28% to 38% of IP patients, most commonly on the vertex11
. Forty percent of IP patients have nail abnormalities12
. Onychogryphosis, pitting, and yellow discoloration have been reported, as have benign subungual dyskeratotic tumors3,4
; a port-wine stain has been reported in one patient with IP12
Between 65% and 80% of IP patients have dental abnormalities3
, such as anodontia, hypodontia, delayed dentition, impaction, pegged teeth, conical crown formation, and accessory cusps3,4,11,12
. In addition, 35% to 40% of IP patients have ocular abnormalities3
, most commonly strabismus, but also including cataracts, keratitis, and optic nerve atrophy3,4,11,12
. Avascularity in the peripheral temporal retina, retinal detachment, and preretinal fibrovascular proliferation with vitreous hemorrhage have also been observed, all of which may lead to blindness3,4,11,12
Between 10% and 31% of IP patients have neurologic symptoms and signs3
. Seizures are the most common symptoms, but mental retardation, microcephaly, spastic or paralytic quadriplegia, hemiplegia, and diplegia have also been reported in IP patients3,4,11,12
. Abnormalities of the musculoskeletal system have been observed, including hemivertebra, hemiatrophy, syndactyly, congenital dislocation of the hip, club foot, dwarfism, kyphoscoliosis, unilateral acheiria, and supernumerary ribs3
. Among the cardiovascular anomalies observed in patients with IP are atrial septal defects, patent ductus arteriosus, acyanotic tetralogy of Fallot (TOF), ventricular endomyocardial fibrosis, tricuspid insufficiency, and primary pulmonary hypertension3,4,11,13
. Cleft lip and palate have been rarely reported14
. Immunologic abnormalities are common in IP5
and include functional abnormalities of neutrophils and lymphocytes and defects in polymorphonuclear chemotaxis.
At her first visit, our patient presented with characteristic whorled brownish patches on her trunk and extremities, and histopathologic findings were consistent with stage III IP. She also had a large perimembranous VSD, left hemiatrophy, hemangiomas, an abnormal labial frenum, and spastic cerebral palsy manifested as left hemiplegia and developmental delay. To our knowledge, although VSD is a relatively common cardiac anomaly estimated to affect up to 1% of babies, there has been only one reported case of an IP patient with TOF, one component of which is a VSD13
. An abnormal labial frenum has also never been reported in an IP patient, and a cutaneous vascular anomaly has been described in only one case of IP, in which a port-wine stain was present. Spastic cerebral palsy with hemiplegia and developmental delay has also been rarely reported in patients with IP, as has hemiatrophy, manifested as a discrepancy in limb length. To date, our patient has shown no dental or ocular abnormalities.
Because IP is a systemic disorder, a multidisciplinary approach to management is crucial. Our patient underwent VSD patch closure under the care of a pediatric cardiac surgeon, and the hemangioma on her back was treated by a dermatologist using a V-beam laser. She is also seeing a rehabilitation specialist for physical therapy of her spastic cerebral palsy. In the future, labial frenectomy should be performed by a dental surgeon. An orthopedic treatment such as the Ilizarov technique may be necessary to balance the length of her limbs. Since she is only 11 months old, careful follow-up examinations by an ophthalmologist and a dentist will be necessary in the upcoming months and years.