sSMC's occur in ring or centric minute (linear with a central centromere) shapes, may contain inverted repeats of its genetic material, and may be an isochromosome.
Cells carrying sSMCs that contain a non-duplicated fragment of a chromosome have one extra copy of the genetic material and are termed trisomic.
[9] The sSMC-associated abnormalities include: mild to serious syndromes recognized congenitally (i.e. at birth) or in the fetus;[5] infertility which is commonly detected in or near adulthood; and benign or malignant tumors that develop at virtually any age.
This is due to at least three mechanisms: 1) differences in the genomic contents of the sSMCs and/or individuals' genomes;[12] 2) variable changes in the genetic material of sSMCs that develop over time;[8] and 3) genetic mosaicism, i.e. variations in the distribution of the sSMC to different tissues and organs that occur during embryonic development or thereafter.
The following sections detail some sSMC-associated disorders that are found in larger numbers of individuals, are genetically well-characterized, and/or exemplify novel aspects or impacts of particular sSMCs.
[citation needed] The Cat eye syndrome (CES), also termed the Schmid–Fraccaro syndrome, is a severe disorder in which individuals have multiple birth defects such as congenital heart abnormalities, renal malformations, craniofacial anormalies, male genital anomalies, skeleton defects, borderline to moderately severe mental retardation, and cat-like downward-slanted openings between the upper and lower eyelids.
A balanced translocation is an even exchange between two chromosomes that results in no change in genetic information and generally has no detrimental effects on its carriers.
[14] A CES-associated sSMC may be small, large, or ring-shaped and typically includes 2 Mb, i.e. 2 million DNA base pairs, termed the CES critical region, located on its q arm at bands 11.1 through ll.23.
[16] Marker chromosome 15 syndrome, also called Isodicentric 15, idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15), is a moderate to severe congenital disorder that includes early-life weakness and hypotonia of the central (but not limb) muscles, delays in normal development, intellectual disability, autistic behavior, epilepsy,[5] stomach/intestinal disorders,[17] and/or brain abnormalities.
Tetrasome 15qter syndrome is an extremely rare congenital syndrome which is associated with mental retardation, overgrowth of the body or body part,[5] skull bossing, short palpebral fissures, long philtrum, low-set ears, high-arched palate, retrognathia (i.e., abnormal posterior positioning of the maxilla or mandible), joint contractions, arachnodactyly, and/or, less commonly, kidney, genitourinary[20] and various vascular and cardiac anomalies.
[21] Emanuel syndrome (ES), also known as supernumerary der(22)t(11;22) syndrome, is characterized by multiple birth defects including craniofacial dysmorphic features, delayed development, mental retardation,[5] ear anomalies, cleft or high-arched palate, micrognathia (i.e. undersized jaw), microcephaly (i.e. shorter-than-normal head), kidney abnormalities, heart defects, and, in males, genital abnormalities.
[22][24] Der(22)t(8;22)(q24.1;q11.1) syndrome, also termed the supernumerary der(22)t(8;22) syndrome, is a syndrome in which individuals are born with normal birth weight and growth but have moderate mental retardation; dysmorphic features in the face and head areas; prominent, low-set, underdeveloped ear canals, and/or preauricular pits (small holes or cysts in front and above the ear canal); clinodactyly (abnormal curvature of one or more fingers and/or toes); and ectopic testis (testes in unusual locations) or cryptorchidism (undescended testes).
Carriers of it are at risk of having progeny with the Der(22)t(8;22)(q24.1;q11.1) syndrome because they acquired a sSMC that has alteration(s) in the parent's abnormal chromosome.
[25] Tetrasomy 9p (also termed 9p isochromosome[5]) is associated with a wide range of birth defects including intrauterine growth retardation; facial dysmorphism; cleft lip and/or palate; malformations of the limbs and skeleton; and/or abnormalities of the central nervous system, heart, and/or genitourinary tract.
Isochromosome i (5p) (also termed tetrasomy 5p[28][29]) is a congenital disorder associated with a wide range of birth defects the most common of which are: developmental delay, hypotonia, short stature, seizures, congenital heart defects, ventriculomegaly (enlargement of the brain's lateral ventricles), shortened survival in the uterus or after birth,[29] psychomotor retardation, facial disfigurements,[28] and/or feeding and/or breathing difficulties.
[29] Isochromosome 18p syndrome,[5] also termed tetrasomy 18p, is a birth disorder associated with microcephaly (shorter than normal head), small kidneys, cryptorchidism, micropenis, hypospadias (i.e. the penis's urethral opening is mis-located), strabismus, feeding difficulties, neonatal jaundice, kyphosis (excessive convex curvature of the spine), scoliosis (sideways curve of the spine), recurrent otitis media, hearing loss, constipation, feeding problems, dysmorphic features,[31] and/or moderately severe mental retardation.
[32] However, a recent report on one individual with the syndrome revealed a sSMC of at least 15 Mb extending from band 11.21 to ll.32 on the p arm of chromosome 18.
Thus, the normal twin appeared to have an extreme form of mosaicism in which the sSMC was present in too few tissue cells to cause the birth defects associated with the isochromosome 15p syndrome.
Extreme levels of sSMC mosaicism in this and possibly other sSMC-associated disorders can be well tolerated, not associated with birth defects, and more common than currently considered.
[33] Recent studies in two individuals with PKS found the sSMC consisted of two small duplications from band 11 to the terminus of the p arm on chromosome 12.
[34][35] A small percentage of Turner syndrome individuals have sSMCs that contain parts of the genetic material from an X or, much less frequently, Y chromosome.
The extremely severe cases have anencephaly (absence of a major portion of the brain, skull, and scalp), agenesis of the corpus callosum (lack of the thick tract of nerve fibers that connect the left and right cerebral hemispheres), and complex heart deformities.
Clinically, women with sSMC-associated infertility have a history of amenorrhea and/or primary ovarian insufficiency, i.e. premature menopause or symptoms related to premenopausal events such as partial or total losses of estrogens, progesterone, androstenedione, activin, and/or inhibin production by the ovaries before age 40.
The term ALT is often applied to tumors located in surgically accessible locations such as the skin, oral cavity, or eye socket whereas the term well-differentiated liposarcomas is applied to tumors in less surgically accessible, deep, and centrally-located, soft tissues such as the retroperitoneum.
[45] As a result of these complicating factors, the specific genetic material in the sSCMs and giant marker chromosomes responsible for the development of ALTs have not been established.
[10] However, both the sSMCs and RGMs in LGO commonly contain parts of various other chromosomes, may be multiple, and often undergo changes in there genetic material during cell divisions.
This partial Y chromosome-bearing sSMC may include the SRY gene located on the p arm of the Y chromosome at band 11.2 (notated as Yp11.2).
Turner syndrome individuals with this SRY gene-containing sSMC have an increased incidence of developing gonadal tissue neoplasms such as gonadoblastomas and in situ seminomas (also termed dysgerminoma to indicate that this tumor has the pathology of the testicular tumor, seminoma, but develops in ovaries[49]).
[50][51][52] Turner syndrome individuals with sSMCs that lacks the SRY gene are not at an increased risk of developing these cancers.
[50] A sSMC containing isochromosome i (5p)(p10) (see above section on the isochcromosome 18p syndrome) has been documented to be present in the malignant cells of certain types of cancer.