Mucolipidosis IV (MLIV) is an ultra-rare lysosomal storage disorder characterized by severe psychomotor delay, progressive visual impairment, and achlorhydria. Individuals with MLIV typically present by the end of the first year of life with delayed developmental milestones (due to a developmental brain abnormality) and impaired vision (resulting from a combination of corneal clouding and retinal degeneration). By adolescence, all individuals with MLIV have severe visual impairment. A neurodegenerative component of MLIV has become more widely appreciated, with the majority of individuals demonstrating progressive spastic quadriparesis and loss of psychomotor skills starting in the second decade of life. About 5% of individuals have atypical MLIV, manifesting with less severe psychomotor impairment, but still exhibiting progressive retinal degeneration and achlorhydria.

Jejunal atresia is the most common cause of bowel obstruction in the newborn. In this condition, because of agenesis of the mesentery, the distal small bowel comes straight off the caecum and twists around the marginal artery, suggesting a maypole, a Christmas tree, or an apple peel at operation. Obliteration of the superior mesenteric artery may underlie this malformation.

A developmental defect in which the gallbladder fails to form.

Blue Diaper syndrome is a hereditary metabolic disorder characterised by hypercalcaemia with nephrocalcinosis and indicanuria.

Juberg-Hayward syndrome (JHS) is characterized by cleft lip and palate, rhizomelia of the upper limbs with limited elbow extension due to humeroradial synostosis or dislocation of the radial head, and digital anomalies, including shortened thumbs and index and fifth fingers. Microcephaly has been observed in some patients (Kantaputra et al., 2020).

The hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas (CRC). Genetic Heterogeneity of Hereditary Mixed Polyposis HMPS2 (610069) is caused by mutation in the BMPR1A gene (601299) on chromosome 10q23.

Graves disease (GRD) is an autoimmune disorder in which antibodies to the thyrotropin receptor (TSHR; 603372) result in constitutive activation of the receptor and increased levels of thyroid hormone. Wilkin (1990) reviewed endocrine disorders of hormone excess and hormone deficiency resulting from receptor autoimmunity. Genetic Heterogeneity of Graves Disease Susceptibility to Graves disease-1 (GRD1) has been mapped to chromosome 14q31. Other susceptibility loci for Graves disease include GRD2 (603388) on chromosome 20q13, GRDX1 (300351) on Xp11, and GRDX2 (see 300351) on Xq21.33-q22. Graves disease has also been mapped to several loci that confer susceptibility to autoimmune thyroid diseases, including Hashimoto thyroiditis (HT; 140300): AITD1 (608173) on 6p11; AITD2 (608174) on 5q31-q33; AITD3 (608175) on 8q24; AITD4 (608176) on 10q, and AITD5 (601941) on 18q21.

A rare genetic skin disorder with characteristics of very early-onset of progressive skin thickening over the entire body (except for eyelids, neck and ears), progressively limited joint mobility with gradual freezing of joints and eventual severe chest and abdomen movement restriction, manifesting with restrictive pulmonary disease, which may lead to death. Additional features include severe growth restriction and osteoporosis. There have been no further descriptions in the literature since 1974.

A rare multiple congenital anomalies/dysmorphic syndrome characterized by auditory canal atresia (resulting in moderate conductive hearing loss) associated with intellectual disability, ventricular septal defect, umbilical hernia, anteriorly displaced anus, various skeletal anomalies (such as mild clubfoot, long fifth fingers, proximally placed thumbs), and craniofacial dysmorphism which includes brachycephaly, prominent forehead, flattened occiput, midface hypoplasia, anteverted nares, and low set, posteriorly rotated ears with overlapping superior helix. There have been no further descriptions in the literature since 1987.

Systemic sclerosis is a clinically heterogeneous connective tissue disorder characterized by immune activation, vascular damage, and fibrosis of the skin and major internal organs. Clinical and experimental data suggest that the disorder is multifactorial, involving both genetic and environmental factors (Fonseca et al., 2007). Gabrielli et al. (2009) provided a detailed review of scleroderma, including clinical manifestations and pathophysiology. See also Reynolds syndrome (613471), which shares some clinical features with scleroderma and CREST syndrome.

Any COACH syndrome in which the cause of the disease is a variation in the TMEM67 gene.

Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).