Monosomy 9p
| Monosomy 9p | |
|---|---|
| Other names | 9p deletion syndrome |
| Specialty | Medical genetics  |
Monosomy 9p (also known as Alfi's Syndrome or simply 9P-) is a rare chromosomal disorder in which some DNA is missing or has been deleted on the short arm region, “p”, of one copy of chromosome 9 (9p22.2-p23).[1][2] This deletion either happens de novo or as a result of a parent having the chromosome abnormality.[3] This rare chromosome abnormality is often diagnosed after birth when development delay, irregular facial features, structural irregularities within the heart, and genital defects are noticed. Treatments for this syndrome usually focus on fixing the common associated malformations.[2] Monosomy 9p was first discovered in 1973 when three infants with similar clinical features were observed to have a partial deletion of the short arm of chromosome 9.[4] Symptoms include micro genitalia, intellectual disability with microcephaly and dysmorphic features.[5]
Signs and symptoms
Psychomotor development delays
Psychomotor development refers to the changes experienced directly after birth through adolescence. Development occurs in cognitive, emotional, motor, and social skills over the child's growth and a delay can result in lagging development of language, motor skills, cognition, or social skills, but these delays can vary in severity.[6][7]
Facial dysmorphism
Facial dysmorphisms broadly describe any abnormalities in facial structure. Facial dysmorphisms include sloping forehead, frontal bossing (prominent protruding forehead), hemifacial microsomia (one side of the face underdeveloped), and otocephaly (absence of mandible and fusion of ears under chin).[8][9]
Malformation of limbs
Congenital limb defects occur when the limbs of a fetus, either upper or lower, experience altered development. These developmental abnormalities include absence of the limb, failure of portions of the limb to separate (commonly fingers and toes), duplication of digits, or overgrowth or undergrowth of limbs.[10]
Genetics
Inheritance pattern
The inheritance pattern for monosomy 9p is inherited in an autosomal dominant inheritance pattern. This means that a single copy of the deletion is sufficient to cause the disease.[11]
Mutation
The mutation, which occurs in the form of a deletion of the short arm of chromosome 9, causes the cell to not express the gene products normally controlled by the genes within the chromosome 9 deletion.[12]
Genes involved
The 9p deletion causes a loss of genes that would normally be there. The signs, symptoms and severity of the condition depend on the specific genes that are lost. Most of the genes involved are associated with the development of tissues.[13]
There are many possible genes that can be deleted, but two particular genes, DMRT1 and DMRT2, are known to be involved. When DMRT1 and DMRT2 are deleted, genital malformations and mental retardation are evident, but the direct mechanisms for these problems remain undefined.[13]
Location
Geneticists originally had the syndrome narrowed down to the short arm region of chromosome 9. Now, the location of the deletion has recently been narrowed to 9p22.2-p23.[1]
Diagnosis
Diagnoses can occur at any age. Most of the time chromosome 9p deletion syndrome is diagnosed after birth by the detection of symptoms via clinical evaluation. Common methods used to detect monosomy 9p after birth include the use of a stethoscope, X-ray, and EKG.[2] Monosomy 9p is also diagnosed before birth by ultrasound, amniocentesis, and chorionic villus sampling (CVS). Ultrasound can hint at the malformations of the face, limbs, and heart, while amniocentesis and CVS both use fluid and tissue to perform chromosomal studies to identify chromosomal abnormalities.[2] Finally, karyotyping, a procedure used to examine a patient's chromosomes, can be used to diagnose monosomy 9p both before birth and after birth.[citation needed]
Management
Treatment of monosomy 9p focuses mainly on fixing the malformations. For example, to fix facial malformations, physicians can perform facial surgery to repair the facial malformations. This can open airways for the infant or patient, especially the nose-to-throat pathway. Similarly, to fix heart malformations, physicians can recommend surgery or medication to improve the efficiency of the pumping of the heart.[2] Lastly remedial education, speech therapy, and physical therapy can be used to improve the developmental delay associated with the syndrome.[2]
Epidemiology
Monosomy 9p occurs 1 in 50,000 births.[14] Half of the cases occur sporadically, while the other half of the cases result from parent translocations or the parent having deletion as well.[2]
References
- ^ a b Kawara, Hiroki; Yamamoto, Toshiyuki; Harada, Naoki; Yoshiura, Koh-ichiro; Niikawa, Norio; Nishimura, Akira; Mizuguchi, Takeshi; Matsumoto, Naomichi (15 February 2006). "Narrowing candidate region for monosomy 9p syndrome to a 4.7-Mb segment at 9p22.2-p23". American Journal of Medical Genetics Part A. 140A (4): 373–377. doi:10.1002/ajmg.a.31094. PMID 16419130. S2CID 32538366.
- ^ a b c d e f g "Chromosome 9, Partial Monosomy 9p". NORD (National Organization for Rare Disorders). Retrieved 2021-04-26.
- ^ "Chromosome 9p deletion syndrome - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-04-26.
- ^ Cakmakkaya, Ozlem Serpil; Bakan, Mefkur; Altintas, Fatis; Kaya, Guner (January 2007). "Anesthetic management in a child with deletion 9p syndrome". Pediatric Anesthesia. 17 (1): 88–89. doi:10.1111/j.1460-9592.2006.02016.x. PMID 17184442. S2CID 38706898.
- ^ "Monosomy 9p - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2024-01-13.
- ^ Cioni, Giovanni; Sgandurra, Giuseppina (2013). "Normal psychomotor development". Pediatric Neurology Part I. Handbook of Clinical Neurology. Vol. 111. pp. 3–15. doi:10.1016/B978-0-444-52891-9.00001-4. ISBN 978-0-444-52891-9. PMID 23622146.
- ^ "Psychomotor Development Retardation (PDR) | Rainbowkids Adoption & Child Welfare Advocacy". RainbowKids.com. Retrieved 2021-04-26.
- ^ Eixarch, Elisenda; Figueras, Francesc; Gómez, Olga; Puerto, Bienvenido (2018). "Facial Dysmorphism". Obstetric Imaging: Fetal Diagnosis and Care: 327–331.e1. doi:10.1016/B978-0-323-44548-1.00069-3. ISBN 978-0-323-44548-1.
- ^ "Chromosome 9, Partial Monosomy 9p - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2024-01-13.
- ^ "Congenital Limb Defects | Boston Children's Hospital". www.childrenshospital.org. Archived from the original on 2021-04-26. Retrieved 2021-04-26.
- ^ "Chromosome 9p deletion syndrome - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-05-01.
- ^ "What is 9p Minus?". www.9pminus.org. Retrieved 2021-05-01.
- ^ a b Climent Alcalá, F.J.; Molina Rodríguez, M.A.; González Casado, I.; Osona Bris, L.; Salamanca Fresno, L.; Guerrero-Fernández, J.; Martínez-Frías, M.L.; Gracia Bouthelier, R. (March 2010). "Deleción 9p-. Disgenesia gonadal asociada a retraso mental e hipoplasia del cuerpo calloso. ¿Síndrome de genes contiguos?" [Chromosome 9P deletion: Gonadal dysgenesis associated with mental retardation and hypoplasia of the corpus callosum: A contiguous gene syndrome?]. Anales de Pediatría (in Spanish). 72 (3): 210–214. doi:10.1016/j.anpedi.2009.10.018. PMID 20138017.
- ^ "What is 9p Minus?". www.9pminus.org. Retrieved 2021-04-26.