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McKusick-Kaufman syndrome(MKKS)

MedGen UID:
184924
Concept ID:
C0948368
Disease or Syndrome
Synonyms: Hydrometrocolpos syndrome; Hydrometrocolpos, postaxial polydactyly, and congenital heart malformation; MKKS
SNOMED CT: Hydrometrocolpos, postaxial polydactyly, and congenital heart malformation (702407009); McKusick Kaufman syndrome (702407009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): MKKS (20p12.2)
 
Monarch Initiative: MONDO:0009367
OMIM®: 236700
Orphanet: ORPHA2473

Disease characteristics

Excerpted from the GeneReview: McKusick-Kaufman Syndrome
McKusick-Kaufman syndrome (MKS) is characterized by the combination of postaxial polydactyly (PAP), congenital heart disease (CHD), and hydrometrocolpos (HMC) in females and genital malformations in males (most commonly hypospadias, cryptorchidism, and chordee). HMC in infants usually presents as a large cystic abdominal mass arising out of the pelvis, caused by dilatation of the vagina and uterus as a result of the accumulation of cervical secretions from maternal estrogen stimulation. HMC can be caused by failure of the distal third of the vagina to develop (vaginal agenesis), a transverse vaginal membrane, or an imperforate hymen. PAP is the presence of additional digits on the ulnar side of the hand and the fibular side of the foot. A variety of congenital heart defects have been reported including atrioventricular canal, atrial septal defect, ventricular septal defect, or a complex congenital heart malformation. [from GeneReviews]
Authors:
Anne M Slavotinek   view full author information

Additional descriptions

From OMIM
McKusick-Kaufman syndrome (MKKS) is an autosomal recessive disorder characterized by genitourinary malformations, especially hydrometrocolpos, polydactyly, and, more rarely, heart or gastrointestinal malformations (summary by Schaefer et al., 2011).  http://www.omim.org/entry/236700
From MedlinePlus Genetics
McKusick-Kaufman syndrome is a condition that affects the development of the hands and feet, heart, and reproductive system. It is characterized by a combination of three features: extra fingers and/or toes (polydactyly), heart defects, and genital abnormalities.

Most females with McKusick-Kaufman syndrome are born with a genital abnormality called hydrometrocolpos, which is a large accumulation of fluid in the pelvis. Hydrometrocolpos results from a blockage of the vagina before birth, which can occur if part of the vagina fails to develop (vaginal agenesis) or if a membrane blocks the opening of the vagina. This blockage allows fluid to build up in the vagina and uterus, stretching these organs and leading to a fluid-filled mass. Genital abnormalities in males with McKusick-Kaufman syndrome can include placement of the urethral opening on the underside of the penis (hypospadias), a downward-curving penis (chordee), and undescended testes (cryptorchidism).

The signs and symptoms of McKusick-Kaufman syndrome overlap significantly with those of another genetic disorder, Bardet-Biedl syndrome. Bardet-Biedl syndrome has several features that are not seen in McKusick-Kaufman syndrome, however. These include vision loss, delayed development, obesity, and kidney (renal) failure. Because some of these features are not apparent at birth, the two conditions can be difficult to tell apart in infancy and early childhood.  https://medlineplus.gov/genetics/condition/mckusick-kaufman-syndrome

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).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Polycystic kidney disease
MedGen UID:
9639
Concept ID:
C0022680
Disease or Syndrome
The presence of multiple cysts in both kidneys.
Vesicovaginal fistula
MedGen UID:
22640
Concept ID:
C0042582
Anatomical Abnormality
The presence of a fistula connecting the urinary bladder to the vagina.
Hydrometrocolpos
MedGen UID:
82843
Concept ID:
C0269209
Disease or Syndrome
Hydrometrocolpos is an accumulation of uterine and vaginal secretions as well as menstrual blood in the uterus and vagina.
Hydroureter
MedGen UID:
101073
Concept ID:
C0521620
Anatomical Abnormality
The distention of the ureter with urine.
Vaginal atresia
MedGen UID:
232948
Concept ID:
C1321884
Congenital Abnormality
Congenital occlusion of the vagina or adhesion of the walls of the vagina causing occlusion.
Transverse vaginal septum
MedGen UID:
341032
Concept ID:
C1856006
Finding
A rare vaginal malformation characterized by the presence of a complete or incomplete transverse septum at any level of the vagina (most frequently the upper or middle third), resulting from incomplete fusion between the Müllerian duct component and the urogenital sinus component of the vagina during embryogenesis. The condition is only rarely diagnosed in neonates or infants, unless it causes significant hydromucocolpos. Complete septa present with primary amenorrhea, cyclic pelvic pain, dyspareunia, or a pelvic mass consisting of accumulated menstrual blood, while incomplete septa may lead to dyspareunia and dysmenorrhea.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism".
Pedal edema
MedGen UID:
116085
Concept ID:
C0239340
Pathologic Function
An abnormal accumulation of excess fluid in the lower extremity resulting in swelling of the feet and extending upward to the lower leg.
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Mesoaxial hand polydactyly
MedGen UID:
893020
Concept ID:
C4021606
Anatomical Abnormality
The presence of a supernumerary finger (not a thumb) involving the third or fourth metacarpal with associated osseous syndactyly.
Imperforate anus
MedGen UID:
1997
Concept ID:
C0003466
Congenital Abnormality
Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.
Rectovaginal fistula
MedGen UID:
11152
Concept ID:
C0034895
Finding
The presence of a fistula between the vagina and the rectum.
Aganglionic megacolon
MedGen UID:
5559
Concept ID:
C0019569
Disease or Syndrome
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008). Total colonic aganglionosis and total intestinal HSCR also occur. Genetic Heterogeneity of Hirschsprung Disease Several additional loci for isolated Hirschsprung disease have been mapped. HSCR2 (600155) is associated with variation in the EDNRB gene (131244) on 13q22; HSCR3 (613711) is associated with variation in the GDNF gene (600837) on 5p13; HSCR4 (613712) is associated with variation in the EDN3 gene (131242) on 20q13; HSCR5 (600156) maps to 9q31; HSCR6 (606874) maps to 3p21; HSCR7 (606875) maps to 19q12; HSCR8 (608462) maps to 16q23; and HSCR9 (611644) maps to 4q31-q32. HSCR also occurs as a feature of several syndromes including the Waardenburg-Shah syndrome (277580), Mowat-Wilson syndrome (235730), Goldberg-Shprintzen syndrome (609460), and congenital central hypoventilation syndrome (CCHS; 209880). Whereas mendelian modes of inheritance have been described for syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance. The development of surgical procedures decreased mortality and morbidity, which allowed the emergence of familial cases. HSCR occurs as an isolated trait in 70% of patients, is associated with chromosomal anomaly in 12% of cases, and occurs with additional congenital anomalies in 18% of cases (summary by Amiel et al., 2008).
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMcKusick-Kaufman syndrome
Follow this link to review classifications for McKusick-Kaufman syndrome in Orphanet.

Professional guidelines

PubMed

Mallmann MR, Reutter H, Mack-Detlefsen B, Gottschalk I, Geipel A, Berg C, Boemers TM, Gembruch U
Fetal Diagn Ther 2019;45(1):62-68. Epub 2018 Feb 23 doi: 10.1159/000486781. PMID: 29478043
Gaucherand P, Vavasseur-Monot C, Ollagnon E, Boisson C, Labaune JM, Basset T, Yared G
Prenat Diagn 2002 Nov;22(11):1048-50. doi: 10.1002/pd.448. PMID: 12424774

Recent clinical studies

Etiology

Phillips MR, Linden AF, Vinocur CD, Hagerty JA
J Pediatr Urol 2019 Oct;15(5):481-483. Epub 2019 Aug 13 doi: 10.1016/j.jpurol.2019.08.001. PMID: 31564590
Baujat G, Le Merrer M
Orphanet J Rare Dis 2007 Jun 4;2:27. doi: 10.1186/1750-1172-2-27. PMID: 17547743Free PMC Article
Andersen KL, Echwald SM, Larsen LH, Hamid YH, Glümer C, Jørgensen T, Borch-Johnsen K, Andersen T, Sørensen TI, Hansen T, Pedersen O
J Clin Endocrinol Metab 2005 Jan;90(1):225-30. Epub 2004 Oct 13 doi: 10.1210/jc.2004-0465. PMID: 15483080
Slavotinek AM, Searby C, Al-Gazali L, Hennekam RC, Schrander-Stumpel C, Orcana-Losa M, Pardo-Reoyo S, Cantani A, Kumar D, Capellini Q, Neri G, Zackai E, Biesecker LG
Hum Genet 2002 Jun;110(6):561-7. Epub 2002 May 9 doi: 10.1007/s00439-002-0733-3. PMID: 12107442
Sheffield VC, Nishimura D, Stone EM
Curr Opin Genet Dev 2001 Jun;11(3):317-21. doi: 10.1016/s0959-437x(00)00196-9. PMID: 11377969

Diagnosis

Halim A, Afzal T, Fatima S, Riaz S
J Coll Physicians Surg Pak 2018 Jun;28(6):S140-S142. doi: 10.29271/jcpsp.2018.06.S140. PMID: 29866251
Parlakgumus A, Yalcinkaya C, Kilicdag E
BMJ Case Rep 2011 Mar 24;2011 doi: 10.1136/bcr.02.2011.3808. PMID: 22699466Free PMC Article
Baujat G, Le Merrer M
Orphanet J Rare Dis 2007 Jun 4;2:27. doi: 10.1186/1750-1172-2-27. PMID: 17547743Free PMC Article
Slavotinek AM, Biesecker LG
Am J Med Genet 2000 Nov 27;95(3):208-15. PMID: 11102925
Stone DL, Agarwala R, Schäffer AA, Weber JL, Vaske D, Oda T, Chandrasekharappa SC, Francomano CA, Biesecker LG
Hum Mol Genet 1998 Mar;7(3):475-81. doi: 10.1093/hmg/7.3.475. PMID: 9467007

Prognosis

Phillips MR, Linden AF, Vinocur CD, Hagerty JA
J Pediatr Urol 2019 Oct;15(5):481-483. Epub 2019 Aug 13 doi: 10.1016/j.jpurol.2019.08.001. PMID: 31564590
Mallmann MR, Reutter H, Mack-Detlefsen B, Gottschalk I, Geipel A, Berg C, Boemers TM, Gembruch U
Fetal Diagn Ther 2019;45(1):62-68. Epub 2018 Feb 23 doi: 10.1159/000486781. PMID: 29478043
Baujat G, Le Merrer M
Orphanet J Rare Dis 2007 Jun 4;2:27. doi: 10.1186/1750-1172-2-27. PMID: 17547743Free PMC Article
Gaucherand P, Vavasseur-Monot C, Ollagnon E, Boisson C, Labaune JM, Basset T, Yared G
Prenat Diagn 2002 Nov;22(11):1048-50. doi: 10.1002/pd.448. PMID: 12424774
Stone DL, Slavotinek A, Bouffard GG, Banerjee-Basu S, Baxevanis AD, Barr M, Biesecker LG
Nat Genet 2000 May;25(1):79-82. doi: 10.1038/75637. PMID: 10802661

Clinical prediction guides

Baujat G, Le Merrer M
Orphanet J Rare Dis 2007 Jun 4;2:27. doi: 10.1186/1750-1172-2-27. PMID: 17547743Free PMC Article
Sheffield VC
Pediatr Res 2004 Jun;55(6):908-11. doi: 10.1203/01.pdr.0000127013.14444.9c. PMID: 15155861
Simpson JL
Am J Med Genet 1999 Dec 29;89(4):224-39. doi: 10.1002/(sici)1096-8628(19991229)89:4<224::aid-ajmg7>3.0.co;2-c. PMID: 10727998
Stone DL, Agarwala R, Schäffer AA, Weber JL, Vaske D, Oda T, Chandrasekharappa SC, Francomano CA, Biesecker LG
Hum Mol Genet 1998 Mar;7(3):475-81. doi: 10.1093/hmg/7.3.475. PMID: 9467007
Lurie IW, Wulfsberg EA
Genet Couns 1994;5(3):275-81. PMID: 7811428

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