mckusick - kaufman and bardet - biedl-6 syndrome are two rare syndromes inherited in an autosomal recessive pattern caused by mutations in mkks gene mapped onto chromosome 20p12 between d20s162-d20s894 markers . the mkks gene has six exons and the atg start codon is in exon 3 . mkks has been cloned and shown to encode a group ii chaperonin - like protein with a wide tissue distribution involved in the folding and structural modification of numerous proteins . the clinical phenotype of mks is characterized by a triad unrelated manifestations that comprises postaxial polydactyly hydrometrocolpos ( hmc present in 70% of affected amish females ) , ( pap present in 60% of affected amish patients ) , and congenital heart disease ( chd present in 15% of amish patients ) . in mks males subjects most commonly are glanular hypospadias , prominent scrotal raphe , cryptorchidism . cardiac malformations described in mks individuals include atrioventricular communis with a left - sided superior vena cava , atrial or ventricular septal defect , small aorta and hypoplastic left ventricle , tetralogy of fallot , and patent ductus arteriosus . bbs syndrome is more genetically heterogeneous than mks and it has been associated to at least 11 genes distributed on different chromosomes . several reports describe bbs phenotypes with three mutant alleles with at least one allele in mkks gene . this syndrome is characterized by several severe clinical manifestations , including retinal dystrophy , hypogenitalism , renal malformations , pap , central obesity , learning disability . although the hypogenitalism , pap , and renal anomalies may be apparent at birth , the other clinical features develop and the complications are severe . hmc , chd and pap defects are a significant clinical overlap between mks and bbs . we report a rare case of female neonate , born in an italian nonconsanguineous healthy family with hmc and pap . the association of hmc and pap in female neonate is compatible with mks or bbs-6 syndromes which are inherited in an autosomal recessive manner . molecular analysis of mkks gene identified two different sequence mutations in heterozygous , i.e. p.242a > s in exon 3 and p.339 i > v in exon 4 and a sequence variation in 5utr region in exon 2 ( -417 a > c ) . the association of hydrometrocolpos ( hmc ) and postaxial polydactyly ( pap ) in female neonate was compatible with mckusick - kaufman syndrome ( mks ) or bardet - biedl-6 syndrome ( bbs-6 ) , two rare human syndrome inherited in an autosomal recessive pattern caused by mutations in mkks gene . generally , hmc and pap are sufficient for a clinical diagnosis of mks in a non - amish female without evidence of overlapping syndromes . it is necessary to follow up the female probands until 5 years of age in order to exclude the presence of other characteristic clinical features or complications present in bbs patients . the close relationship between mks and bbs-6 has been further complicated by the demonstration of disease - causing sequence alterations in the mkks gene in both mks and in an estimated 4 to 6% of unselected individuals with bbs . we report a rare case of female neonate born in an italian nonconsanguineous healthy family with hmc and pap . the mother ( 32 years ) and the father ( 37 years ) , and beside mother 's allergy to gramineous , other anamnestic data were negative . birth weight was 2 550 g with a length of 42 cm ( < 3 centiles ) and a head circumference of 31.3 cm ( < 3 centiles ) . the proband presents postaxial hexadactyly [ figure 1 ] , and a large abdominal mass displacing the intestine and elevating the diaphragms ( panel a ) . abdominal magnetic resonance imaging ( mri ) [ figure 2 ] revealed a large cystic mass originating from the pelvic floor and hmc , fluid - filled that compressed and displaced the urinary bladder anteriorly . with a bladder catheter about 150 cc of brown fluid accumulated was drainage . we performed complete mutation screening by sequencing six exons of mkks gene with relative intron - exon boundary region and the alternatively spliced 5 exons . photograph of the hands shows postaxial polydactyly with six digits on either hand ( postaxial hexadactyly ) panel a shows a large lower abdominal mass at birth ( hydrometrocolpos ) . cor t2 w ) shows large abdominal cystic mass communicating with endometrial lumen molecular analysis of mkks gene identified two different sequence mutations in heterozygous , i.e. , p.242ala > ser in exon 3 and p.339 ile > val in exon 4 and a sequence variation in 5utr region in exon 2 ( -417 a > c ) . the a242s has been reported as a potential bbs susceptibility factor and play a major role in the pathogenesis of nonsyndromic obesity , age dependent , in combination with other obesity genes . the i339v was previously identified without other coding sequence alterations in bbs patients [ figure 3 ] . a schematic representation of the mkks gene locus and mutations identifi ed ( panel a ) and chromatographs ( panel b ) showing the sequence variation p.242a > s in exon 3 ( left ) and the sequence variation p.339i > v in exon 4 ( right ) in the proband ( pt ) and a control subject ( wt ) . the mutations identified in mkks gene suggest strictly relationship with hmc and pap phenotype , but the definitively diagnosis should be revaluated to exclude phenotypic bbs age - dependent features . special attention should be paid on the organs ( hart , eyes , kidneys , gonads ) and age - dependent comparison of signs such as cone dystrophy , obesity , learning disability , and renal dysfunction . the above mentioned signs are characteristics of bbs , which is the final diagnosis for major number of patients even for those whose first diagnosis is mks . the patient 's follow up should be reinforced with other types of useful support such as diet and psychological .
mckusick - kaufman syndrome ( mks , omim # 236700 ) is a rare syndrome inherited in an autosomal recessive pattern with a phenotypic triad comprising hydrometrocolpos ( hmc ) , postaxial polydactyly ( pap ) , and congenital cardiac disease ( chd ) . 
 the syndrome is caused by mutations in the mkks gene mapped onto chromosome 20p12 between d20s162 and d20s894 markers . 
 mutations in the same gene causes bardet - biedl-6 syndrome ( bbs-6 , omim # 209900 ) inherited in an autosomal recessive pattern . 
 bbs-6 comprises retinitis pigmentosa , polydactyly , obesity , mental retardation , renal and genital anomalies . 
 hmc , chd , and pap defects can also occur in bbs-6 , and there is a significant clinical overlap between mks and bbs-6 in childhood . 
 we describe a new borderline case of mks and bbs syndrome and suggest insights for understanding correlation between mkks gene mutations and clinical phenotype . here 
 , we report the results of molecular analysis of mkks in a female proband born in an italian nonconsanguineous healthy family that presents hmc and pap . 
 the mutational screening revealed the presence of two different heterozygous missense variants ( p.242a > s in exon 3 , p.339 i > v in exon 4 ) in the mkks gene , and a nucleotide variation in 5utr region in exon 2 ( -417 a > c ) .