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Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay(CAKUTHED)

MedGen UID:
1612119
Concept ID:
C4539968
Disease or Syndrome
Synonyms: CAKUTHED; CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT SYNDROME WITH OR WITHOUT HEARING LOSS, ABNORMAL EARS, OR DEVELOPMENTAL DELAY
 
Gene (location): PBX1 (1q23.3)
 
Monarch Initiative: MONDO:0060549
OMIM®: 617641

Definition

CAKUTHED is an autosomal dominant highly pleiotropic developmental disorder characterized mainly by variable congenital anomalies of the kidney and urinary tract, sometimes resulting in renal dysfunction or failure, dysmorphic facial features, and abnormalities of the outer ear, often with hearing loss. Most patients have global developmental delay (summary by Heidet et al., 2017 and Slavotinek et al., 2017). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Horseshoe kidney
MedGen UID:
65140
Concept ID:
C0221353
Congenital Abnormality
A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.
Ectopic kidney
MedGen UID:
68661
Concept ID:
C0238207
Congenital Abnormality
A developmental defect in which a kidney is located in an abnormal anatomic position.
Unilateral renal agenesis
MedGen UID:
75607
Concept ID:
C0266294
Congenital Abnormality
A unilateral form of agenesis of the kidney.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Ambiguous genitalia
MedGen UID:
78596
Concept ID:
C0266362
Congenital Abnormality
A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale
Renal agenesis
MedGen UID:
154237
Concept ID:
C0542519
Congenital Abnormality
Agenesis, that is, failure of the kidney to develop during embryogenesis and development.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Absence of renal corticomedullary differentiation
MedGen UID:
342352
Concept ID:
C1849765
Finding
A lack of differentiation between renal cortex and medulla on diagnostic imaging.
Decreased numbers of nephrons
MedGen UID:
436031
Concept ID:
C2673888
Finding
A reduction in the count of nephrons per kidney.
Hyperechogenic kidneys
MedGen UID:
477530
Concept ID:
C3275899
Finding
An increase in amplitude of waves returned in ultrasonography of the kidney, which is generally displayed as increased brightness of the signal.
Renal dysplasia
MedGen UID:
760690
Concept ID:
C3536714
Congenital Abnormality
The presence of developmental dysplasia of the kidney.
Bifid ureter
MedGen UID:
854360
Concept ID:
C3887498
Congenital Abnormality
Incomplete duplication of the ureter.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Vascular dilatation
MedGen UID:
8076
Concept ID:
C0002940
Pathologic Function
Abnormal outpouching or sac-like dilatation in the wall of an atery, vein or the heart.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Thickened helices
MedGen UID:
325240
Concept ID:
C1837732
Finding
Increased thickness of the helix of the ear.
Hypoplastic helices
MedGen UID:
334588
Concept ID:
C1842681
Finding
Underdevelopment of the helix, i.e., of the outer rim of the pinna.
Anteverted ears
MedGen UID:
384047
Concept ID:
C1857055
Finding
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Congenital diaphragmatic hernia
MedGen UID:
68625
Concept ID:
C0235833
Congenital Abnormality
The presence of a hernia of the diaphragm present at birth.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Deep philtrum
MedGen UID:
374311
Concept ID:
C1839797
Finding
Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Professional guidelines

PubMed

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Recent clinical studies

Etiology

Sorge I, Hirsch FW, Fuchs M, Gräfe D, Dietz A, Sorge M
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Pediatr Dermatol 2004 May-Jun;21(3):191-6. doi: 10.1111/j.0736-8046.2004.21301.x. PMID: 15165194

Diagnosis

Morrison D, Kesser B
Otolaryngol Clin North Am 2023 Oct;56(5):933-948. Epub 2023 Aug 1 doi: 10.1016/j.otc.2023.06.007. PMID: 37537101
Sorge I, Hirsch FW, Fuchs M, Gräfe D, Dietz A, Sorge M
Rofo 2023 Oct;195(10):896-904. Epub 2023 Jun 22 doi: 10.1055/a-2081-4119. PMID: 37348530
Cubitt JJ, Chang LY, Liang D, Vandervord J, Marucci DD
J Paediatr Child Health 2019 May;55(5):512-517. Epub 2019 Mar 28 doi: 10.1111/jpc.14444. PMID: 30920067
Phelan PJ, Rheault MN
Pediatr Nephrol 2018 Oct;33(10):1671-1683. Epub 2017 Nov 12 doi: 10.1007/s00467-017-3835-9. PMID: 29130116
Ječmenica J, Bajec-Opančina A, Ječmenica D
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Therapy

Tang D, Li H, Chen L
Adv Exp Med Biol 2019;1130:109-128. doi: 10.1007/978-981-13-6123-4_7. PMID: 30915704
Liberman MC, Kujawa SG
Hear Res 2017 Jun;349:138-147. Epub 2017 Jan 10 doi: 10.1016/j.heares.2017.01.003. PMID: 28087419Free PMC Article
Schilder AG, Chonmaitree T, Cripps AW, Rosenfeld RM, Casselbrant ML, Haggard MP, Venekamp RP
Nat Rev Dis Primers 2016 Sep 8;2(1):16063. doi: 10.1038/nrdp.2016.63. PMID: 27604644Free PMC Article
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Morgan T
Am Fam Physician 2007 Aug 1;76(3):405-10. PMID: 17708142

Prognosis

Kim J, Jeong M, Yang S, Han JH, Bae SH
Otol Neurotol 2023 Dec 1;44(10):1033-1037. Epub 2023 Sep 20 doi: 10.1097/MAO.0000000000004023. PMID: 37733987
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Henkemans SE, Smit AL, Stokroos RJ, Thomeer HGXM
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van Beeck Calkoen EA, Engel MSD, van de Kamp JM, Yntema HG, Goverts ST, Mulder MF, Merkus P, Hensen EF
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Celmina M, Micule I, Inashkina I, Audere M, Kuske S, Pereca J, Stavusis J, Pelnena D, Strautmanis J
Clin Genet 2019 Jan;95(1):63-78. Epub 2018 Jul 8 doi: 10.1111/cge.13374. PMID: 29722015

Clinical prediction guides

Yeon EK, Son HO, Sung HJ, Choi JW
Otolaryngol Head Neck Surg 2023 Oct;169(4):1028-1034. Epub 2023 Apr 1 doi: 10.1002/ohn.341. PMID: 37003293
Zalzal HG, Lawlor CM
JAMA Otolaryngol Head Neck Surg 2023 Apr 1;149(4):360-367. doi: 10.1001/jamaoto.2023.0001. PMID: 36862403
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Genes (Basel) 2023 Jan 28;14(2) doi: 10.3390/genes14020335. PMID: 36833263Free PMC Article
Sennaroğlu L, Bajin MD
Balkan Med J 2017 Sep 29;34(5):397-411. Epub 2017 Aug 25 doi: 10.4274/balkanmedj.2017.0367. PMID: 28840850Free PMC Article
Mathur P, Yang J
Biochim Biophys Acta 2015 Mar;1852(3):406-20. Epub 2014 Dec 4 doi: 10.1016/j.bbadis.2014.11.020. PMID: 25481835Free PMC Article

Recent systematic reviews

Kessi M, Chen B, Peng J, Yan F, Yang L, Yin F
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Oh DL, Jerman P, Silvério Marques S, Koita K, Purewal Boparai SK, Burke Harris N, Bucci M
BMC Pediatr 2018 Feb 23;18(1):83. doi: 10.1186/s12887-018-1037-7. PMID: 29475430Free PMC Article
Ruzbarsky JJ, Scher D, Dodwell E
Curr Opin Pediatr 2016 Feb;28(1):40-6. doi: 10.1097/MOP.0000000000000302. PMID: 26709689
Moeschler JB, Shevell M; Committee on Genetics
Pediatrics 2014 Sep;134(3):e903-18. doi: 10.1542/peds.2014-1839. PMID: 25157020Free PMC Article
Law J, Garrett Z, Nye C
Cochrane Database Syst Rev 2003;2003(3):CD004110. doi: 10.1002/14651858.CD004110. PMID: 12918003Free PMC Article

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