History
A 22-month-old girl is referred with a persistent colour change in a patchy distribution over her body. She is otherwise well and fully vaccinated to date. She was born post-term at 41 weeks’ gestation by normal vaginal delivery. Her mother reports that she had a blistering skin rash at birth and a ‘high white cell count’. She was treated with antibiotics for one week on the neonatal unit and had extensive tests to rule out viral illness, all of which were negative. Her mother shares neonatal photos and is certain that the areas of colour change do not correspond with the areas of previous blistering.
Her family history is remarkable in that her maternal grandmother recalls her mother suf-fering from a similar transient neonatal blistering eruption. She has an older sister aged 7 years and her mother has been investigated for recurrent miscarriages.
Examination
The girl is clearly thriving with height and weight between the 75th and 91st centiles for her age. She has achieved age-appropriate developmental milestones. She has strik- ing linear streaked and whorled areas of brown hyperpigmentation, predominantly over her trunk but also involving her legs. Figure 93.1 shows a well-defined, irregular linear streak of hyperpigmentation extending along the dorsal aspect of her left leg. The distri-bution of the colour changes corresponds with Blaschko’s lines. She has marked ridging of three fingernails and one toenail. All twenty of her deciduous teeth have erupted; she has two peg-shaped teeth. Her mother is also happy to be examined and she has subtle skin changes composed of fine pale, hairless, atrophic, ‘porcelain’-like streaks over her posterior calves. She has two hypoplastic nails and one conical tooth.
Questions
• What is the diagnosis?
• What is the implication of this diagnosis?
• What is the explanation for the distri-bution of the hyperpigmentation?
Medicine
This is the classical clinical scenario of an uncommon genodermatosis called inconti-nentia pigmenti (IP). Skin features are subdivided into four stages: vesicular, verrucous, hyperpigmented, and atrophic. There are various hair, nail, dental, ophthalmological and neurological anomalies described in association with IP. The differential diagnosis of the neonatal vesicular stage, which is typically associated with a peripheral eosinophilia, includes infections (bullous impetigo, herpes simplex, varicella), Langerhans cell histio-cytosis, epidermolysis bullosa, bullous mastocytosis and autoimmune blistering diseases.
IP is an X-linked dominant disorder, lethal in the majority of males in utero, explaining the mother’s recurrent miscarriages. The pathogenic mutation occurs within the NEMO/ IKK gene. Genetic testing is available, although prenatal testing is not generally offered as prognosis for affected females is generally excellent and affected male fetuses do not generally survive into the second trimester. Clinical presentations vary, even among family members (Table 93.1). The differences in clinical phenotype expression are attributed to lyonization resulting in functional mosai-cism, which in the skin manifests along the curvilinear lines of Blaschko. These represent random X-inactivation and migration of clonal epidermal cells along embryological developmental lines. Cells expressing the mutated X chromosome selectively eliminate, and affected females have an extremely skewed X-inactivation pattern.
KEY POINTS
• Incontinentia pigmenti (IP) is an uncommon genodermatosis with effects on the neuroectoderm.
• IP is an X-linked dominant disease, lethal to affected males in utero.
• Clinical features vary according to the random inactivation of the affected X chromosome and vary with age.
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