Thrombocytopenia absent radius (TAR) syndrome is characterized by bilateral absence of the radii with the presence of both thumbs, and thrombocytopenia that is generally transient. Thrombocytopenia may be congenital or may develop within the first few weeks to months of life; in general, thrombocytopenic episodes decrease with age. Cow's milk allergy is common and can be associated with exacerbation of thrombocytopenia. Other anomalies of the skeleton (upper and lower limbs, ribs, and vertebrae), heart, and genitourinary system (renal anomalies and agenesis of uterus, cervix, and upper part of the vagina) can occur.

PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral edema (summary by Anttonen et al., 2017).

Hereditary angioedema-5 (HAE5) is an autosomal dominant disorder characterized by localized and self-limiting edema of the subcutaneous or submucosal tissue due to an episodic increase in vascular permeability. Affected individuals have onset of episodic swelling of the face, lips, hands, and abdomen in the second decade of life. Treatment with tranexamic acid may be effective in reducing the severity and frequency of the attacks (summary by Bafunno et al., 2018). For a discussion of genetic heterogeneity of hereditary angioedema, see 106100.

Hereditary angioedema-6 (HAE6) is an autosomal dominant disorder characterized by onset of episodic subcutaneous and submucosal swelling in adulthood. The face, mouth, and tongue are often affected; some patients have distal limb or abdominal edema. Levels of complement component inhibitor (C1INH; 606860) are normal (summary by Bork et al., 2019). For a discussion of genetic heterogeneity of HAE, see 106100.

Hereditary angioedema-8 (HAE8) is an autosomal dominant disorder characterized clinically by recurrent and self-limited episodes of localised edema in various organs, including the face, tongue, larynx, and extremities. In rare cases, swelling of the tongue or larynx can lead to airway obstruction. Abdominal attacks may also occur, resulting in abdominal pain, vomiting, and diarrhea. The disorder results from enhanced vascular permeability (summary by Bork et al., 2021). For a discussion of genetic heterogeneity of HAE, see 106100.