Ectodermal dysplasia is characterized by abnormal development of structures derived from embryonal ectoderm (nail, hair, teeth, and sweat glands).
NEMO Deficiency - Patients develop pointed conical incisors, sparse hair, and absent sweat glands. In addition its role in immune functions, NF-B is also involved in the differentiation of ectodermal structures.
Dyskeratosis congenita - Patients clasically develop nail dystrophy [which ranges from mild (ridging and flaking) to severe (almost complete nail loss)], sparse hair, oral leukoplakia, and skin hypo or hyperpigmentation. Telomeres in rapidly dividing cells (ex. skin, hair, and nails) reach critical lengths sooner, triggering premature cell senescence or apoptosis.
APECED - Enamel hypoplasia is a common finding (77% of patients). Patchy alopecia may also occur. One-half of APECED patients develop nail pitting and nail dystrophy.
Chronic Mucocutaneous Candidiasis - Patients develop nail dystrophy secondary to Candida infections.
STAT3 Deficiency (Hyper IgE syndrome) - Patients develop nail dystrophy secondary to Candida infections. Patients with AD Hyper IgE (STAT 3) syndrome can also have delayed shedding of primary teeth.
ORAI1 and STIM 1 deficiency - Patients have anhydrotic ectodermal dysplasia which presents as an inability to sweat and defective calcification of the dental enamel matrix (loss of dental enamel results in painful exposure of underlying dentin). Other features of ectodermal dysplasia such as hair and nail abnormalities have not been reported. Patients also have a non-progressive myopathy as well as severe combined immunodeficiency.