A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring. Ring chromosomes were first discovered by Lilian Vaughan Morgan in 1926. [1] A ring chromosome is denoted by the symbol r in human genetics and R in Drosophila genetics. Ring chromosomes may form in cells following genetic damage by mutagens like radiation, but they may also arise spontaneously during development.
In order for a chromosome to form a ring, both ends of the chromosome are usually missing, enabling the broken ends to fuse together. In rare cases, the telomeres at the ends of a chromosome fuse without any loss of genetic material, which results in a normal phenotype. [2]
Complex rearrangements, including segmental microdeletions and microduplications, have been seen in numerous ring chromosomes, providing important clues regarding the mechanisms of their formation. [3]
Small supernumerary rings can also form, resulting in a partial trisomy. [4]
Ring chromosomes are unstable during cell division and can form interlocking or fused rings. [4]
Human genetic disorders can be caused by ring chromosome formation. Although ring chromosomes are very rare, they have been found in all human chromosomes. Symptoms seen in patients carrying ring chromosomes are more likely to be caused by the deletion of genes in the telomeric regions of affected chromosomes, rather than by the formation of a ring structure itself. [5] Almost all ring chromosome syndromes feature marked growth delay. [4]
Ring chromosomes can be inherited or sporadic. Mosaicism is common and affects the severity of the condition. [5] Location of fusion also affects severity due to loss of differing amounts of genetic material from the ends of chromosomes.
Disorders arising from the formation of a ring chromosome include:
| Chromosome | Typical features | |
|---|---|---|
| Ring chromosome 1 | Microcephaly, facial abnormalities | [6] |
| Ring chromosome 2 | Small stature | [7] [8] |
| Ring chromosome 3 | [9] | |
| Ring chromosome 4 | Craniofacial abnormalities | [10] |
| Ring chromosome 5 | [11] | |
| Ring chromosome 6 | Microcephaly, facial abnormalities, hand abnormalities | [12] |
| Ring chromosome 7 | Craniofacial abnormalities, speech deficits | [13] |
| Ring chromosome 8 | Craniofacial abnormalities, hydronephrosis, hand abnormalities | [14] |
| Ring chromosome 9 | Delayed growth, abnormal facial features, low muscle tone | [15] |
| Ring chromosome 10 | Delayed growth, facial dysmorphism, reproductive abnormalities | [16] |
| Ring chromosome 11 | [17] | |
| Ring chromosome 12 | Delayed growth, abnormal facial features, microcephaly | [18] [19] |
| Ring chromosome 13 | Microcephaly, delayed growth, reproductive abnormalities | [20] |
| Ring chromosome 14 | Epilepsy, intellectual disability | [21] |
| Ring chromosome 15 | Growth delay, microcephaly, intellectual disability | [22] |
| Ring chromosome 16 | Microcephaly, growth delay, facial abnormalities | [23] [24] |
| Ring chromosome 17 | [25] | |
| Ring chromosome 18 | Growth delay, facial abnormalities | [26] |
| Ring chromosome 19 | [27] | |
| Ring chromosome 20 | Epilepsy, abnormal facial features, growth delay | [28] |
| Ring chromosome 21 | Short stature, microcephaly, reproductive abnormalities | [29] |
| Ring chromosome 22 | Hypotonia, autistic-like behavior | [30] |
| Ring chromosome X | Turner syndrome | |
| Ring chromosome Y | [31] |
Autoimmune polyendocrine syndromes (APSs), also called polyglandular autoimmune syndromes (PGASs) or polyendocrine autoimmune syndromes (PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. There are three types of APS, and there are a number of other diseases which involve endocrine autoimmunity.
Acromicric dysplasia is an extremely rare inherited disorder characterized by abnormally short hands and feet, growth retardation and delayed bone maturation leading to short stature. Most cases have occurred randomly for no apparent reason (sporadically). However, autosomal dominant inheritance has not been ruled out.
SCARF syndrome is a rare syndrome characterized by skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, psychomotor retardation, and facial abnormalities. These characteristics are what make up the acronym SCARF. It shares some features with Lenz-Majewski hyperostotic dwarfism. It is a very rare disease with an incidence rate of approximately one in a million newborns. It has been clinically described in two males who were maternal cousins, as well as a 3-month-old female. Babies affected by this syndrome tend to have very loose skin, giving them an elderly facial appearance. Possible complications include dyspnea, abdominal hernia, heart disorders, joint disorders, and dislocations of multiple joints. It is believed that this disease's inheritance is X-linked recessive.
Gray platelet syndrome (GPS), or platelet alpha-granule deficiency, is a rare congenital autosomal recessive bleeding disorder caused by a reduction or absence of alpha-granules in blood platelets, and the release of proteins normally contained in these granules into the marrow, causing myelofibrosis. The name derives from the initial observation of gray appearance of platelets with a paucity of granules on blood films from a patient with a lifelong bleeding disorder.
Naegeli–Franceschetti–Jadassohn syndrome (NFJS), also known as chromatophore nevus of Naegeli and Naegeli syndrome, is a rare autosomal dominant form of ectodermal dysplasia, characterized by reticular skin pigmentation, diminished function of the sweat glands, the absence of teeth and hyperkeratosis of the palms and soles. One of the most striking features is the absence of fingerprint lines on the fingers.
Upington disease is an extremely rare autosomal dominant malformation disorder. It has only one published source claiming its existence in three generations of one family from South Africa.
Chronic mucocutaneous candidiasis is an immune disorder of T cells. It is characterized by chronic infections with Candida that are limited to mucosal surfaces, skin, and nails. It can also be associated with other types of infections, such as human papilloma virus. An association with chromosome 2 has been identified.
GRACILE syndrome is a very rare lethal autosomal recessive genetic disorder, one of the Finnish heritage diseases. GRACILE syndrome has also been found in the UK and Sweden, but not nearly as much as in Finland. It is caused by a mutation in the BCS1L gene and it occurs in approximately 1 out of 50,000 live births in Finnish people. To date, there have only been 32 cases of GRACILE syndrome reported.
Morgagni–Stewart–Morel syndrome is a condition with a wide range of associated endocrine problems including: diabetes mellitus, diabetes insipidus, and hyperparathyroidism. Other signs and symptoms include headaches, vertigo, hirsutism, menstrual disorder, galactorrhoea, obesity, depression, and seizures. It is characterized by a thickening of the inner table of the frontal part of the skull, a usually benign condition known as hyperostosis frontalis interna. The syndrome was first described in 1765. It is named after the Italian anatomist and pathologist Giovanni Battista Morgagni, the British neurologist Roy Mackenzie Stewart, and the Swiss psychiatrist Ferdinand Morel.
Sialuria is a group of disorders resulting in an accumulation of free sialic acid. One type, known as the Finnish type or Salla disease has been described in northeastern Finland and is due to a mutation in gene SLC17A5 on chromosome 6q4-15. The "French type sialuria", is a very rare condition presenting in infancy with failure to thrive, yellowish skin, large liver, low blood count, recurrent chest infections, bowel upsets, dehydration and characteristic facial features.
Lyngstadaas syndrome, also known as severe dental aberrations in familial steroid dehydrogenase deficiency, is a rare autosomal recessive liver disease involving an enzyme deficiency and dental anomalies. The disease is named after the Norwegian professor Ståle Petter Lyngstadaas.
Gordon syndrome, or distal arthrogryposis type 3, is a rare genetic disorder characterized by cleft palate and congenital contractures of the hands and feet.
Mietens syndrome is a autosomal recessive disorder first described by Mietens and Weber. The condition is named after a German physician named Carl Mietens.
Nathalie syndrome is a rare genetic developmental defect during embryogenesis disorder and is thought to be hereditary.
Jones syndrome is an extremely rare disorder characterized by gingival fibromatosis and sensorineural hearing loss. The condition is an inherited but the underlying genetic cause is currently unknown.
van Den Bosch syndrome is a rare X-linked syndrome like intellectual disability. It may be caused by a small X-chromosome deletion.
Blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome is a very rare genetic and congenital disorder which is characterized by blepharophimosis, ptosis, V-esotropia, foot syndactyly, extra-ocular and frontal muscles weakness, low height/short stature, prognathism, and synophrys.
Stocco dos Santos syndrome is an extremely rare multi-systemic genetic disorder which is present from birth. It is characterized by heart, skeletal, muscular abnormalities with accompanying intellectual disabilities.
Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare genetic disorder characterized by spondylometaphyseal dysplasia, neonatal growth delays, and cone-rod dystrophy-associated progressive vision loss. Only 18 patients from families in the United States, the United Kingdom, Japan, and Brazil have been described to date. This condition is caused by autosomal recessive mutations in the PCYT1A gene, located in chromosome 3.