Mandibuloacral dysplasia with type B lipodystrophy (MADB) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies such as mandibular hypoplasia, skeletal anomalies such as progressive osteolysis of the terminal phalanges and clavicles, and skin changes such as mottled hyperpigmentation and atrophy. The lipodystrophy is characterized by generalized loss of subcutaneous fat involving the face, trunk, and extremities. Some patients have a progeroid appearance. Metabolic complications associated with insulin resistance have been reported (Schrander-Stumpel et al., 1992; summary by Simha et al., 2003). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370).

Lipodystrophy-intellectual disability-deafness syndrome is an extremely rare form of genetic lipodystrophy (see this term), reported in 3 patients from one family to date, characterized by generalized congenital lipodystrophy, low birth weight, progressive sensorineural deafness occurring in childhood, intellectual deficit, progressive osteopenia, delayed skeletal maturation, skeletal abnormalities described as slender, undermineralized tubular bones, and dense metaphyseal striations in the distal femur, ulna and radius of older patients. Autosomal recessive inheritance has been suggested.

Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis, and early onset of diabetes (Garg, 2004). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).

Keppen-Lubinsky syndrome (KPLBS) is a rare disorder characterized by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth (summary by Masotti et al., 2015).

The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development (Takenouchi et al., 2013). Takenouchi et al. (2013) noted phenotypic overlap with Marfan syndrome (154700) and Shprintzen-Goldberg craniosynostosis syndrome (182212).

Mandibuloacral dysplasia progeroid syndrome (MDPS) is an autosomal recessive severe laminopathy-like disorder characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis, and hypertension (Elouej et al., 2020).

Proteasome-associated autoinflammatory syndrome-4 (PRAAS4) is an autosomal recessive immunologic disorder characterized by onset of panniculitis and erythematous skin lesions in early infancy. Additional features include hepatosplenomegaly, lymphadenopathy, fever, generalized lipodystrophy, myositis, and joint contractures, as well as delayed motor and speech development. Autoimmune features, such as hemolytic anemia, may also occur. Laboratory studies show elevation of acute phase reactants and abnormal activation of the type I interferon response. Treatment with the JAK (see 147795) inhibitor ruxolitinib may result in clinical improvement (summary by de Jesus et al., 2019). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).