Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.

Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe psychomotor retardation, mild dysmorphism, and impaired neutrophil motility. It is a member of a group of disorders with a defect in the processing of protein-bound glycans. For a general overview of congenital disorders of glycosylation (CDGs), see CDG1A (212065) and CDG2A (212066). Frydman (1996) contended that the neutrophil defect in CDG2C, which has been referred to as 'leukocyte adhesion deficiency type II' (LAD2), is a manifestation of the disorder and that there are no cases of 'primary' LAD II. Etzioni and Harlan (1999) provided a comprehensive review of both leukocyte adhesion deficiency-1 (LAD1; 116920) and LAD2. While the functional neutrophil studies are similar in the 2 LADs, the clinical course is milder in LAD2. Furthermore, patients with LAD2 present other abnormal features, such as growth and mental retardation, which are related to the primary defect in fucose metabolism. Delayed separation of the umbilical cord occurs in LAD1. For a discussion of genetic heterogeneity of LAD, see 116920.

Kabuki syndrome (KS) is characterized by typical facial features (long palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows; short columella with depressed nasal tip; large, prominent, or cupped ears), minor skeletal anomalies, persistence of fetal fingertip pads, mild-to-moderate intellectual disability, and postnatal growth deficiency. Other findings may include: congenital heart defects, genitourinary anomalies, cleft lip and/or palate, gastrointestinal anomalies including anal atresia, ptosis and strabismus, and widely spaced teeth and hypodontia. Functional differences can include: increased susceptibility to infections and autoimmune disorders, seizures, endocrinologic abnormalities (including isolated premature thelarche in females), feeding problems, and hearing loss.

Bare lymphocyte syndrome type I (BLS I) is an inherited disorder of the immune system (primary immunodeficiency). Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria or viruses. Starting in childhood, most people with BLS I develop recurrent bacterial infections in the lungs and airways (respiratory tract). These recurrent infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems.\n\nMany people with BLS I also have open sores (ulcers) on their skin, usually on the face, arms, and legs. These ulcers typically develop in adolescence or young adulthood. Some people with BLS I have no symptoms of the condition.\n\nPeople with BLS I have a shortage of specialized immune proteins called major histocompatibility complex (MHC) class I proteins on cells, including infection-fighting white blood cells (lymphocytes), which is where the condition got its name.

Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) is an autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies (summary by Zhou et al., 2012).

Bardet-Biedl syndrome-16 (BBS16) is an autosomal recessive ciliopathy characterized by retinal degeneration, obesity, renal disease, and cognitive impairment. Although polydactyly is considered a primary feature of BBS overall, it has not been reported in any BBS16 patient (Billingsley et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).