Kabuki Syndrome

Congenital syndrome characterized by multiple congenital anomalies, typical facial features (regardless of ethnic origin), and mild-to-moderate mental retardation. Significant cardiac malformations have been reported.

Kabuki Make-up Syndrome; Niikawa-Kuroki Syndrome.

First described in 1980 by the two Japanese physicians N. Niikawa and Y. Kuroki. Phenotype resembles the make-up of actors in Kabuki (traditional Japanese theater). However, patients and their relatives often dislike the term “make-up.”

1:32,000 of Japanese newborns; less in non-Japanese.

Autosomal dominant, arising from sporadic mutations; equal male-to-female ratio. The genetic defect has been mapped to 8p22-23.1.

Unknown. Resembles a genetic disorder; however, there is little evidence regarding the mode of inheritance.

Niikawa and Kuroki described five major groups of abnormalities: (a) abnormal facies, eversion of lower lateral eyelid, arched eyebrows (sparse in the lateral third), depressed nasal tip and prominent ears; (b) skeletal anomalies; (c) dermatoglyphic anomalies; (d) mental retardation; and (e) postnatal growth deficiency.

Skeletal abnormalities include high-arched palate, cleft palate, scoliosis, sagittal cleft vertebrae, vertebral osteopenia, dysplasia of femoral acetabulum, and brachydactyly. Early breast development is seen in 23% of girls. Congenital heart disease is reported in approximately one-third of patients, including single ventricle with common atrium, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta (often juxtaductal), patent ductus arteriosus, transposition of the great arteries, and right bundle branch block. Hepatic anomalies such as extrahepatic biliary atresia and neonatal sclerosing cholangitis have been described and required liver transplantation in some patients.

Kidney anomalies (fused kidneys) and ureteropelvic stenoses with hydronephrosis may result in renal failure.

Stenosis of the upper airway (main bronchus), abnormal branching pattern of the lower airways, and bronchomalacia have been reported in a few patients. Congenital diaphragmatic hernia is occasionally present. More than half of these patients have a form of hearing loss (conductive and/or sensorineural). Recurrent otitis media is a common finding. Dental anomalies (e.g., conical incisors, hypodontia) are not uncommon.

Obtain a history of developmental problems. Make specific inquiries for major skeletal and cardiac abnormalities and previous cardiac surgery. Check renal and hepatic function. Airway assessment, congenital defects of spinal column, mid-face hypoplasia, high arched palate, and cleft palate may make airway management difficult. Respiratory function should be assessed carefully in the presence of scoliosis, and formal lung function tests prior to major surgery may be helpful. Assessment of the cardiac function should include a complete history and examination, ECG, and echocardiography. Cardiac catheterization as clinically indicated. Seizures are not uncommon, so assess therapy and its efficiency.

Prepare for a potentially difficult airway. Strictly avoid air bubbles in all intravascular lines in patients with cardiac defects and carefully maintain the ratio of pulmonary to systemic vascular resistance, depending on individual cardiac anatomy and presence of systemic to pulmonary shunts. Consider the need for postoperative intensive care unit admission after major surgery. Careful airway monitoring in the early postoperative period. Careful positioning is required to avoid joint dislocations (especially hips). Patients with Kabuki syndrome have a strong susceptibility to infections.

No specific contraindications described. Avoid muscle relaxants until the airway has been secured. Consider interactions between anesthetic drugs and chronic antiseizure medications. Subacute bacterial endocarditis prophylaxis may be indicated. Congenital heart disease may dictate avoidance of high-dose volatile agents (decreased systemic vascular resistance resulting in increased right-to-left shunting). The potential need for vasopressors, pulmonary vasodilators, and beta blockers depends on the nature of the cardiac lesion.

Van der Woude Syndrome: Autosomal dominant inherited craniofacial syndrome with cleft lip and/or palate and typical pits of the lower lip, caused by deletions in chromosome band 1q32; can occasionally be associated to Kabuki syndrome.