McKusick-Kaufman syndrome

Ajit Gandhi, MD.*, Anish Dekhane, MD.**

*   Maternal Fetal Medicine Unit, Unique Hospital, Main Road, Solapur, MH, India.
**  Department of pathology, Unique Hospital, Main Road, Solapur, MH, India.

 

Introduction

McKusick–Kaufman Syndrome was initially described by McKusick and further defined by Kaufman and colleagues. More than 60 cases of this syndrome have been described so far.
This is an autosomal recessive syndrome with variable expression within the same family, different families and different sex. Heterozygous are asymptomatic. There is a known mutation in 20p12 in the MKKS gene.

Syndrome is more frequent in females. In males, the findings are limited to finger abnormalities and sometimes genital abnormalities such as hypospadias or micropenis. The final diagnosis can not be made until at least age five years.

Findings in affected females include hydrometrocolpos, postaxial polydactyly and sometimes cardiac defects. Hydrometrocolpos can be caused by failure of the distal third of vagina to develop, a transverse vaginal membrane or imperforate hymen. Cardiovascular malformations include atrial and ventricular septal defect, AV canal, small aorta and hypoplastic left ventricle, tetralogy of Fallot and patent ductus arteriosus. Retrograde flow of the secretion collected in the vagina into the peritoneal cavity can lead to fetal ascites. The increased vaginal secretion is caused by an high level of maternal estrogen.

Differential Diagnosis

Bardet Biedl syndrome, phenotypic differences between these two syndromes become evident later in life, usually after the age of 4-5 years. Bardet Biedl syndrome has a significant morbidity and mortality due to rod-cone atrophy leading to blindness and obesity, compared to a more benign nature of McKusick-Kaufman syndrome when not associated with cardiac defects.
The close relationship between Bardet Biedl syndrome and McKusick-Kaufman syndrome has been further complicated by alterations in the MKKS gene in both McKusick-Kaufman syndrome and in 4-6 % of individuals with Bardet Biedl syndrome. Highlighting this diagnostic limitation at the time of prenatal diagnosis is crucial during the counseling.

Ellis van Creveld syndrome, which is characterized by chondrodysplasia with acromelic growth retardation, polydactyly, ectodermal dysplasia with dystrophy of the nails, and congenital heart disease.


Case report

A G1 P0 of unknown age was referred to our maternal fetal medicine unit for the finding of fetal ascites. Patient came from a Indian family, Laman community with a high incidence of consanguineous marriage and low socioeconomic status.
She did not know her last menstrual period. Her biometry corresponded with 26-27 weeks of gestation. During our ultrasound examination, we detected the following findings:

  • Ascites
  • Hydrometrocolpos; anechogenic round mass, posterior to the urinary bladder
  • Postaxial polydactyly of the lower limbs

Fetal cardiac examination was normal. There was no sign of fetal hydrops. We performed an aspiration of the ascitis. Ascitis can be caused by retrograde flow of the secretion collected in the vagina into the peritoneal cavity.
The cytology result showed presence of non-keratinized estrogenized squamous cells. These cells are normally found in the superficial layer of vaginal wall which is affected by high levels of maternal estrogen. Retrograde flow of the secretion collected in the vagina into the peritoneal cavity can lead to fetal ascites.

Our diagnosis based on the ultrasound findings, was McKusick-Kaufman syndrome.

Images 1,2: Sagittal view of the lower abdomen; urinary bladder (yellow), hydrometrocolpos (blue).

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Images 3,4: Transverse view of the lower abdomen; urinary bladder (yellow), hydrometrocolpos (blue).

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Images 5,6: Sagittal view of the abdomen, note the ascites.

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Images 7,8: Image 7 shows a normal 4-chamber view. Image 8 shows umbilical arteries.

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Images 9,10: Image 9 shows a 3D - image of the fetal face. Image 10 shows a female genitalia, see arrow.

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Images 11,12: Foot with postaxial polydactyly.

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Image 13: Cytology from the ascitis showed nonkeratinized squamous cells.

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Video 1,2: Video 1 shows the sagittal view of the fetal abdomen, note hydrometrocolpos and ascitis. Video 2 shows a female genitalia.



Video 3,4: Transverse view of the lower abdomen.

 


Video 5: Frontal view of the abdomen, note hydrometrocolpos.



References:

1.Gaucherand P, Vavasseur-Monot C, Ollagnon E, Boisson C, Labaune J-M. McKusik-Kaufman syndrome: prenatal diagnosis, genetics and follow up. Prenatal Diagnosis. 2002; 22: 1048-1050.

2.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. Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients. Hum Genet. 2002; 110: 561–7.

3.Beales PL, Katsanis N, Lewis RA, Ansley SJ, Elcioglu N, Raza J, Woods MO, Green JS, Parfrey PS, Davidson WS, Lupski JR. Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci. Am J Hum Genet. 2001; 68: 606–16.

4.OMIM, McKusick-Kaufman syndrome, MIM #236700.

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