User:Lsquil/OLES2129/Draft

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This article explores COACH syndrome, a rare genetic disorder.

COACH syndrome[edit]

COACH syndrome is a medical condition involving the hypoplasia of the cerebellar vermis, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis. It is an autosomal recessive disorder, and falls under the category of a Joubart Syndrome related disorder (JSRD) [1]. The syndrome was first described in 1974 by Alasdair Hunter and his peers at the Montreal Children’s hospital[2]. The report identified two siblings, a brother and sister, presenting with all 5 components of COACH syndrome. It was not until 1989 that it was labelled COACH syndrome, by Verloes and Lambotte, at the Sart- Tilman University Hospital, Beligum [3].

Signs and Symptoms[edit]

An example of coloboma of the eye

Signs of COACH syndrome tend to present from birth to early childhood. Facial abnormalities are a common symptom, with some characteristics being broadness of the forehead, ptosis of either one or both eyes and misalignment of the eyes [4]. Other cases also report a “carp” shaped mouth, flattened face and nose and hypertelorism [3]. Patients are often within the lower percentiles for height and weight growth [1]. Hypotonia is a possible sign of COACH syndrome, known as "Floppy baby syndrome", is a condition that causes low muscle tone, and therefore decreased function[1]. Infants suffering from COACH syndrome may experience very categorical hyper- ventilation and complications with respiration, such as irregular breathing. It has been reported that as patients surpass infancy, these respiratory issues may disappear [5]. Behavioral and intellectual delays are symptoms caused by the hypoplasia of the cerebellar vermis and oligophrenia[6][7] . This implies delayed onset of speech and walking, along with learning and social issues [2]. Poor motor skills and balance, speech impairment, mild gait or hand ataxia and irregular eye movement are symptoms of the disease attributed to congential ataxia[8] . Coloboma of the eye is visible in the retina as “hole” in its structure, and causes low vision, possible sensitivity to light and variance in size of the eyeball[9] [10]. The build-up of tissue in the liver, known as hepatic fibrosis, may cause symptoms such as jaundice[1], ascites, abnormal bleeding and enlarged spleen[11]. Renal disease or nephronophthisis may also be symptoms present in a patient suffering from COACH syndrome, due to reduced function of the kidneys[12].

Genetics[edit]

Due to generational familial linkage and the frequency of siblings sharing inheritance of COACH syndrome, it is classified as an autosomal recessive disorder . COACH syndrome is a ciliopathy, a group of diseases categorized by irregular behavior of the primary cilia, which are involved in cell division, transportation, communication and tissue differentiation. This leads to irregular tissue growth in organs and various other diseases[4]. 83% of COACH syndrome carriers presented with either 1 or 2 mutations on the MKS3 gene, and findings suggest this is where most of the symptoms can be accredited. CC2D2A and RPGRIP1L genes may also have some minor contributions, with around 8.7% reporting a mutation on the CC2D2A gene and 4.3% on the RPGRIP1L gene. These 3 genetic mutations reportedly cover 96% of families suffering from COACH syndrome [12].

Diagnosis[edit]

The diagnosis of COACH syndrome is based off the presence of all five categories; cerebellar vermis hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis.

Detection of the hypoplasia of the cerebrellar vermis is achieved through a cranial magnetic resonance imaging (MRI) scan. The presence of the ‘molar tooth sign’ (MTS) on the MRI scan,  a mid- brain hind- brain malformation, confirms this condition and is a key indicator of COACH syndrome. The MTS’s distinguished shape is attributed to the lengthened superior cerebellar peduncles and deepened interpeduncular fossa[4]. To diagnose ataxia, both neurological assessment and physical examination are required. This can include MRI scans, study of behavior and motor skills in infancy and analysis of family history and genetics. In the case of congenital ataxia, patients are born with the condition and thus diagnosis is more difficult, therefore diagnosis of ataxia alone is not sufficient to indicate COACH syndrome, and must be used in conjunction with other symptoms[13]. Hepatic fibrosis has a range of diagnostic techniques, including invasive and non- invasive. Liver biopsy examination is an invasive technique, while non- invasive methods include ultrasonography- based tests and serum tests [14].

Treatment[edit]

A diagram of dialysis treatment for renal complications

There is no cure for COACH, syndrome, therefore treatment targets the various complications it implies and management of the disease and its symptoms.

Management includes monitoring patients’ neurological activity, development patterns and renal and hepatic function annually. Programs for special education and occupational therapy for speech and motor impairment can improve symptoms of the disease and quality of life [4].

Ophthalmological surgery may be used to treat coloboma and ptosis of the eye to improve vision and appearance. If kidney function is abnormal, dialysis is an effective treatment option, or in more severe cases, a kidney transplant[4]. Hepatic fibrosis has a variety of treatment options, including anti- fibrotic methods, which aim to prevent the build-up of tissue in the liver. In cases of extreme fibrosis causing liver failure, liver transplant surgery is necessary to restore function [12][14].



Prognosis[edit]

Joubert syndrome affects approximately 1 in 80,000 to 1 in 100,000 live births, meaning it is a rare disease. COACH syndrome is categorised as a Jobert syndrome related disorder (JSRD), and therefore its prevalence can be estimated as even more rare, with only 43 cases of COACH syndrome being reported from its discovery until 2010[1]. Due to this rarity, prognosis of the disease is dealt with case- by- case. Survival depends on severity of the symptoms, with most patients surviving infancy[4]. The likely causes of death with progression of time are renal and hepatic failure [15].

References[edit]

  1. ^ a b c d e Weiland, M. David; Nowicki, Michael J.; Jones, Jason K.; Giles, Henry W. (2011-5). "COACH syndrome: an unusual cause of neonatal cholestasis". The Journal of Pediatrics. 158 (5): 858–858.e1. doi:10.1016/j.jpeds.2010.11.056. ISSN 1097-6833. PMID 21237470. {{cite journal}}: Check date values in: |date= (help)
  2. ^ a b Hunter, A. G.; Rothman, S. J.; Hwang, W. S.; Deckelbaum, R. J. (1974). "Hepatic fibrosis, polycystic kidney, colobomata and encephalopathy in siblings". Clinical Genetics. 6 (2): 82–89. ISSN 0009-9163. PMID 4430157.
  3. ^ a b Verloes, A.; Lambotte, C. (1989-2). "Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis". American Journal of Medical Genetics. 32 (2): 227–232. doi:10.1002/ajmg.1320320217. ISSN 0148-7299. PMID 2929661. {{cite journal}}: Check date values in: |date= (help)
  4. ^ a b c d e f Parisi, Melissa A. (2009-11-15). "Clinical and molecular features of Joubert syndrome and related disorders". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 151C (4): 326–340. doi:10.1002/ajmg.c.30229. ISSN 1552-4876. PMC PMCPMC2797758. PMID 19876931. {{cite journal}}: Check |pmc= value (help)
  5. ^ Acharyya, B. C.; Goenka, M. K.; Chatterjee, S.; Goenka, U. (2014-02-01). "Dealing with congenital hepatic fibrosis? Remember COACH syndrome". Clinical Journal of Gastroenterology. 7 (1): 48–51. doi:10.1007/s12328-013-0418-6. ISSN 1865-7265.
  6. ^ "Cerebellar Hypoplasia Information Page | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 2019-05-15.
  7. ^ "Chapter 20: Oligophrenia (Congenital Dementia)". Soviet Law and Government. 8 (2–4): 377–392. 1969-10-01. doi:10.2753/RUP1061-194008020304377. ISSN 0038-5530.
  8. ^ Fogel, Brent L. (2012-9). "Childhood Cerebellar Ataxia". Journal of child neurology. 27 (9): 1138–1145. doi:10.1177/0883073812448231. ISSN 0883-0738. PMC PMCPMC3490706. PMID 22764177. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)
  9. ^ Barzilai, M.; Ish-Shalom, N.; Lerner, A.; Iancu, T. C. (1998-4). "Imaging findings in COACH syndrome". AJR. American journal of roentgenology. 170 (4): 1081–1082. doi:10.2214/ajr.170.4.9530063. ISSN 0361-803X. PMID 9530063. {{cite journal}}: Check date values in: |date= (help)
  10. ^ "Facts About Coloboma | National Eye Institute". nei.nih.gov. Retrieved 2019-05-15.
  11. ^ "Facts About Coloboma | National Eye Institute". nei.nih.gov. Retrieved 2019-05-15.
  12. ^ a b c Doherty, D; Parisi, M A; Finn, L S; Gunay-Aygun, M; Al-Mateen, M; Bates, D; Clericuzio, C; Demir, H; Dorschner, M (2010-1). "Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)". Journal of medical genetics. 47 (1): 8–21. doi:10.1136/jmg.2009.067249. ISSN 0022-2593. PMC PMCPMC3501959. PMID 19574260. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)
  13. ^ Fogel, Brent L. (2012-9). "Childhood Cerebellar Ataxia". Journal of child neurology. 27 (9): 1138–1145. doi:10.1177/0883073812448231. ISSN 0883-0738. PMC PMCPMC3490706. PMID 22764177. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)
  14. ^ a b "Advances in the diagnosis and treatment of liver fibrosis". hrjournal.net. Retrieved 2019-05-17.
  15. ^ Brancati, Francesco; Dallapiccola, Bruno; Valente, Enza Maria (2010-07-08). "Joubert Syndrome and related disorders". Orphanet Journal of Rare Diseases. 5 (1): 20. doi:10.1186/1750-1172-5-20. ISSN 1750-1172.{{cite journal}}: CS1 maint: unflagged free DOI (link)


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