Posterior amelia with pelvic and pulmonary hypoplasia syndrome (PAPPAS) is characterized by absent lower limbs, severely hypoplastic or absent pelvic bones, and hypoplasia of the sacrum, as well as hypoplasia of the lungs with pulmonary segmentation defect. Ambiguous genitalia have also been observed (Kariminejad et al., 2019). Heterozygous mutation in the TBX4 gene causes ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension (ICPPS; 147891).

Brachial amelia, cleft lip, and holoprosencephaly (ACLH) is a severe multiple congenital anomaly disorder characterized by brachial amelia, cleft lip, and forebrain defects consistent with holoprosencephaly. Although the disorder is rarely reported, the features are consistent enough to constitute a distinct entity (summary by Kariminejad et al., 2009).

Diaphragmatic defect-limb deficiency-skull defect syndrome is characterized by the association of classical diaphragmatic hernia (Bochdalek type) with severe lung hypoplasia, and variable associated malformations.

Tetraamelia syndrome-2 (TETAMS2) is characterized by rudimentary appendages or complete absence of the limbs, usually symmetric, as well as bilateral agenesis of the lungs. There are abnormalities of the pulmonary vasculature and dysmorphic features, including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, microretrognathia, and labioscrotal fold aplasia (Szenker-Ravi et al., 2018). For a discussion of genetic heterogeneity of TETAMS, see 273395.