Clinical characteristics: 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.
Diagnosis/testing: The clinical diagnosis of MKS can be established in a proband based on clinical diagnostic criteria of HMC and PAP in the absence of clinical or molecular genetic findings suggestive of an alternative diagnosis. The molecular diagnosis can be established in proband with suggestive findings and biallelic pathogenic variants in MKKS identified by molecular genetic testing. However, care must be taken to ensure that the proband does not have Bardet-Biedl syndrome, an allelic condition with considerable clinical overlap and age-dependent features including retinal dystrophy, obesity, and intellectual disability.
Management: Treatment of manifestations: Surgical repair of the obstruction causing HMC and drainage of the accumulated fluid. Treatment for polydactyly and congenital heart defects and any other anomalies is standard.
Surveillance: Watch for recurrent later complications of surgery for HMC; ongoing surveillance for manifestations of BBS including growth and developmental assessments, ophthalmologic examination, and electroretinogram, renal anomaly complications and development of severe constipation (which raises the possibility of Hirschsprung disease).
Agents/circumstances to avoid: Care with anesthesia in the neonatal period as severe HMC can cause diaphragmatic compression.
Genetic counseling: MKS is inherited in an autosomal recessive manner. If both parents of an individual with MKS are known to be heterozygous for an MKKS pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. (Note: Genetic counseling should encourage caution regarding premature diagnosis of MKS [i.e., a diagnosis made before age 5 years] because of the possibility of manifestations of Bardet-Biedl syndrome appearing at a later age.) Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the MKKS pathogenic variants have been identified in the family. Although HMC, PAP, and CHD can be detected by prenatal ultrasound examination, the reliability of prenatal ultrasound as a method of prenatal diagnosis of MKS is unknown because these findings are variable and may not be apparent in an individual until after birth.
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