Table 2.

Genes of Interest in the Differential Diagnosis of CHILD Syndrome

Gene(s)DisorderMOIKey Features of Disorder
Overlapping w/CHILD syndromeDistinguishing from CHILD syndrome
EBP Chondrodysplasia punctata 2, X-linked XL
  • ≥95% of affected persons are female.
  • Linear or blotchy scaly ichthyosiform plaques in newborns; later appearance of linear or whorled atrophic patches involving hair follicles (follicular atrophoderma) & scarring
  • Asymmetric limb shortening, kyphoscoliosis, & chondrodysplasia punctata (epiphyseal stippling)
  • Absence of strict midline demarcation & lack of unilaterality seen in CHILD syndrome
  • Skin findings fade over time.
  • Most persons have follicular atrophoderma by age 2 yrs.
  • Ocular anomalies are prominent (develop early in life).
HRAS
KRAS
NRAS 		Schimmelpenning-Feuerstein-Mims syndrome (OMIM 163200) & other epidermal nevus syndromes (ENSs)See footnote 1.
  • Skin lesions (epidermal nevi) can be flat, verrucous, inflammatory or non-inflammatory, scaly or non-scaly; they typically follow lines of Blaschko & many grow over time.
  • In Schimmelpenning-Feuerstein-Mims syndrome face &/or scalp are typically involved.
  • Extensive epidermal nevi (various subtypes); unilateral or bilateral
  • Cerebral anomalies & neurologic symptoms
  • Coloboma of iris, choroid, or eyelids
  • Conjunctival lipodermoid
  • Overgrowth & other vascular lesions seen in some ENSs
IKBKG (formerly NEMO) Incontinentia pigmenti XL
  • Embryonic lethality in many males
  • Skin lesions present as erythema & then blisters at birth (vesicular stage), progress to wart-like rash (verrucous stage), swirling macular hyperpigmentation following lines of Blaschko (hyperpigmented stage), & then linear hypopigmentation (hypopigmented stage). 2
  • Cutaneous lesions evolve through multiple stages.
  • Hypodontia
  • Onychogryphosis
  • Ocular findings (mostly retinal; peripheral neovascularization in eyes)
  • Seizures
  • ID

ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

1.

Not known to be inherited. Postzygotic somatic mosaic pathogenic variants in HRAS, KRAS, or NRAS have been reported in lesional tissue of some individuals with Schimmelpenning-Feuerstein-Mims syndrome. Most epidermal nevus syndromes are associated with postzygotic somatic pathogenic variants.

2.

The evolution of the four skin stages in incontinentia pigmenti may or may not occur in all individuals.

From: NSDHL-Related Disorders

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