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    Topic review

    Burn-McKeown Syndrome

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    Submitted by: Catherine Yang
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    Burn-McKeown syndrome is a disorder that is present from birth (congenital) and involves abnormalities of the nasal passages, characteristic facial features, hearing loss, heart abnormalities, and short stature.

    1. Introduction

    In people with Burn-McKeown syndrome, both nasal passages are usually narrowed (bilateral choanal stenosis) or completely blocked (bilateral choanal atresia), which can cause life-threatening breathing problems in infancy without surgical repair. Typical facial features include narrow openings of the eyelids (short palpebral fissures); a gap (coloboma) in the lower eyelids; widely spaced eyes (hypertelorism); a prominent bridge of the nose; a short space between the nose and the upper lip (philtrum); a small opening of the mouth (microstomia); and large, protruding ears.

    Some people with Burn-McKeown syndrome have congenital hearing loss in both ears which varies in severity among affected individuals. The hearing loss is described as mixed, which means that it is caused by both changes in the inner ear (sensorineural hearing loss) and changes in the middle ear (conductive hearing loss).

    Other features that can occur in Burn-McKeown syndrome include mild short stature and congenital heart defects such as patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Intelligence is unaffected in Burn-McKeown syndrome.

    2. Frequency

    Burn-McKeown syndrome is a rare disorder; its prevalence is unknown. Only a small number of affected individuals have been described in the medical literature.

    3. Causes

    Burn-McKeown syndrome is caused by mutations in the TXNL4A gene or in an area of genetic material near the TXNL4A gene called the promoter region, which controls the production of protein from the gene. The TXNL4A gene provides instructions for making one part (subunit) of a protein complex called the major spliceosome, which is the larger of two types of spliceosomes found in human cells. Spliceosomes help process messenger RNA (mRNA), which is a chemical cousin of DNA that serves as a genetic blueprint for making proteins. Spliceosomes recognize and then remove regions called introns from immature mRNA molecules to help produce mature mRNA.

    The mutations affecting the TXNL4A gene that cause Burn-McKeown syndrome reduce the amount of protein produced from the gene. Research suggests that reduced quantities of this spliceosome subunit affect the assembly of the major spliceosome and change the production of a particular group of mRNA molecules. The details of these changes and their relationship to the specific signs and symptoms of Burn-McKeown syndrome are unknown. However, mutations in several genes involved in spliceosome formation or function have been shown to cause other conditions with abnormalities affecting the head and face (craniofacial malformations), so craniofacial development is thought to be particularly sensitive to spliceosome problems.

    4. Inheritance

    This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

    5. Other Names for This Condition

    • bilateral choanal atresia, cardiac defects, deafness, and dysmorphic appearance
    • BMKS
    • choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome
    • oculo-oto-facial dysplasia
    • oculootofacial dysplasia
    • OOFD

    This entry is adapted from https://medlineplus.gov/genetics/condition/burn-mckeown-syndrome

    References

    1. Burn J, McKeown C, Wagget J, Bray R, Goodship J. New dysmorphic syndrome with choanal atresia in siblings. Clin Dysmorphol. 1992 Jul;1(3):137-44.
    2. Hing AV, Leblond C, Sze RW, Starr JR, Monks S, Parisi MA. A noveloculo-oto-facial dysplasia in a Native Alaskan community with autosomal recessiveinheritance. Am J Med Genet A. 2006 Apr 15;140(8):804-12.
    3. Lehalle D, Wieczorek D, Zechi-Ceide RM, Passos-Bueno MR, Lyonnet S, Amiel J,Gordon CT. A review of craniofacial disorders caused by spliceosomal defects.Clin Genet. 2015 Nov;88(5):405-15. doi: 10.1111/cge.12596.Review.
    4. Toriello HV, Higgins JV. A boy with choanal atresia and cardiac defect:Burn-McKeown syndrome? Clin Dysmorphol. 1999 Apr;8(2):143-5.
    5. Wieczorek D, Gillessen-Kaesbach G. Oculo-oto-facial dysplasia (OOFD) versusBurn-McKeown syndrome. Am J Med Genet A. 2006 Nov 1;140(21):2381-2; author reply 2383-4.
    6. Wieczorek D, Newman WG, Wieland T, Berulava T, Kaffe M, Falkenstein D, BeetzC, Graf E, Schwarzmayr T, Douzgou S, Clayton-Smith J, Daly SB, Williams SG,Bhaskar SS, Urquhart JE, Anderson B, O'Sullivan J, Boute O, Gundlach J, Czeschik JC, van Essen AJ, Hazan F, Park S, Hing A, Kuechler A, Lohmann DR, Ludwig KU,Mangold E, Steenpaß L, Zeschnigk M, Lemke JR, Lourenco CM, Hehr U, Prott EC,Waldenberger M, Böhmer AC, Horsthemke B, O'Keefe RT, Meitinger T, Burn J, LüdeckeHJ, Strom TM. Compound heterozygosity of low-frequency promoter deletions andrare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome. Am J Hum Genet. 2014 Dec 4;95(6):698-707. doi: 10.1016/j.ajhg.2014.10.014.
    7. Wieczorek D, Teber OA, Lohmann D, Gillessen-Kaesbach G. Two brothers withBurn-McKeown syndrome. Clin Dysmorphol. 2003 Jul;12(3):171-4.
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