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Monosomy 9p
editClinical Features
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The most common features among individuals with Monosomy 9p are the merging of the two frontal bones in the skull resulting in a triangular shaped forehead (see trigonocephaly), broad nasal bridge, malformed external ears, abnormally large distance between the eyes (see hypertelorism), an abnormal increase in muscle tension (see hypertonia), and intellectual disability in conjunction with delayed motor development[1]. In many cases, these patients also exhibit genital abnormalities (see gonadal dysgenesis)[2].
Cytogenetics
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Monosomy 9p arises from an unbalanced chromosome rearrangement during the recombination of homologous chromosomes that can be spontaneous or inherited[3]. In this case, the short arm region of chromosome 9 (9p), undergoes a partial deletion due to an uneven recombination with another chromosome (known as a translocation). This ultimately leaves the genome with only one copy of the gene located on 9p[4]. Most of the time, these partial deletions cause a double stranded break in the DNA between 9p23-9p22 [5] and result in common clinical features listed above (see 1.1. Clinical Features). However, in cases where the patient exhibits gonadal dysgenesis, the break includes 9p24.3. This region contains a gene identified as DMRT1 that is involved in male sex determination that, when deleted, leaves the individual with only one functional copy of the DMRT1 gene. Since humans normally have two copies, this mutation results in genital abnormalities[6].
In a study done by Alfi et al. in 1973, the researchers examined two unrelated individuals with Monosomy 9p. Cytogenetic tests done on the relatives of the patient indicated that the deletion can be inherited since, in both cases, the parents (the mother in one case, and the father in the other) were carriers of a similar deletion on Chromosome 9[7].
Diagnosis
editSince the disease is chromosomal in nature and arises during egg and sperm production, it is possible to diagnose the phenotype of the fetus (while in the uterus) in the first or second trimesters via three prenatal diagnosis techniques: ultrasound, amniocentesis, and chorionic villus sampling (CVS)[8].
Ultrasounds allow for the non-invasive, observation of the fetus with the naked eye. Since Monosomy 9p is known to exhibit gross facial malformations (see 1.1. Clinical Features), this type of prenatal screening helps to determine whether or not the fetus is showing any early signs of these features. It is performed every 12-20 weeks of gestation to track progression of fetal development[9].
CVS and amniocentesis on the other hand, are far more invasive as amniocentesis requires a sample of the amniotic fluid and CVS requires trophoblastic cell samples. In both cases, even though they are invasive, they are considered safe. These tests are able to determine if the fetus has any chromosomal abnormalities, and can therefore detect the presence of a monosomy at 9p in the genome of the fetus[10].
Possible Treatments
editCurrently, there is no cure for Monosomy 9p. However, there are treatments that can help lower the severity of the symptoms. For example, since some of the most common features are facial deformities, patients affected by the disease are able to undergo craniofacial (head and face) surgery to correct the abnormalities[11].
Furthermore, cognitive-behavioural intervention can be highly effective in Monosomy 9p patients who tend to exhibit intellectual disability[12]. This approach is often used in conjunction with medication, and focuses on the patient’s ability to learn and adapt to their environment in order to live and function normally[13]. Similarly, physical and speech therapy can aid in reducing the severity of the patient’s delayed motor development[14]. In this case, physical and speech therapy does not tend to use medication, but uses appropriate exercises developed specifically for the patient to help them regain control of motor and speech function[15].
References
edit- ^ http://www.omim.org/entry/158170
- ^ Quinonez S, Park J, et al. (2013) "9p partial monosomy and disorders of sex development: review and postulation of a pathogenic mechanism" Am J Med Genet 161 1882-1896
- ^ Kardon N.B. (2002) “NORD Guide to Rare Disorders”. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins
- ^ Thompson and Thompson (2015) Genetics in Medicine: Eighth Edition. Philadelphia, Pennsylvania: Elsevier
- ^ http://www.omim.org/entry/158170
- ^ Quinonez S, Park J, et al. (2013) "9p partial monosomy and disorders of sex development: review and postulation of a pathogenic mechanism" Am J Med Genet 161 1882-1896
- ^ Alfi, O., Donnell, G. N., Crandall, B. F., Derencsenyi, A., Menon, R. Deletion of the short arm of chromosome #9 (46,9p-): a new deletion syndrome. Ann. Genet. 16: 17-22, 1973.
- ^ Pyeritz R.E. (2014). Fundamentals of Human Genetics. In Papadakis M.A., McPhee S.J., Rabow M.W. (Eds), Current Medical Diagnosis & Treatment 2015
- ^ Pyeritz R.E. (2014). Fundamentals of Human Genetics. In Papadakis M.A., McPhee S.J., Rabow M.W. (Eds), Current Medical Diagnosis & Treatment 2015
- ^ Pyeritz R.E. (2014). Fundamentals of Human Genetics. In Papadakis M.A., McPhee S.J., Rabow M.W. (Eds), Current Medical Diagnosis & Treatment 2015
- ^ Kardon N.B. (2002) “NORD Guide to Rare Disorders”. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins
- ^ Thompson T. and Hollon S.D. (2008) “Current Diagnosis & Treatment: Psychiatry”. USA: McGraw-Hill Companies
- ^ Thompson T. and Hollon S.D. (2008) “Current Diagnosis & Treatment: Psychiatry”. USA: McGraw-Hill Companies
- ^ Kardon N.B. (2002) “NORD Guide to Rare Disorders”. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins
- ^ Keenan M. E. et al. (2014) “Current Diagnosis & Treatment in Orthopaedics, Fifth Edition”. USA: McGraw-Hill Education Companies