Kabuki syndrome in Adult
The syndrome includes 5 cardinal features: 1) distinctive facial characteristics, 2) skeletal abnormalities (scoliosis, vertebra malformations, rib and cranial bone abnormalities, and brachydactyly of the fifth digit), 3) dermatoglyphic abnormalities ("padded" fingertips), 4) mild to moderate intellectual disability, and 5) postnatal growth deficiency. Facial hallmarks notably include a broad forehead, long palpebral fissures and long lashes, long earlobes, and an arched or cleft palate. Additionally, other comorbidities are often seen in patients with KS, such as cardiovascular defects (atrial septal defects, ventricular septal defects, and coarctation of the aorta), urogenital defects (hydronephrosis, kidney hypoplasia, and cryptorchidism), and immunological deficiencies (IgA deficiency more common than IgG deficiency; occasionally panhypogammaglobulinemia is seen). It is not uncommon for patients with KS to be small of stature throughout their lives.
Two associated mutations include KDM6A on chromosome X and KMT2D (formerly MLL2) on chromosome 12. Both mutations lead to premature stop codons and nonfunctional enzymes. KDM6A is inherited in an X-linked dominant manner and KMT2D-related KS in an autosomal dominant manner. A small minority of patients with KS do not exhibit either of these mutations; the genetic locus in these patients is unknown.
Q89.8 – Other specified congenital malformations
313426007 – Kabuki make-up syndrome
Differential Diagnosis & Pitfalls
- CHARGE syndrome (cleft lip / palate seen with coloboma, heart defects, choanal atresia, retardation, genital and ear abnormalities)
- 22q11.2 deletion syndrome (cleft lip / palate and congenital defects affecting a broad array of organs, typical facial and fingertip features of KS absent)
- Van der Woude syndrome (cleft lip / palate and pits, sinuses of lower lip)
- Popliteal pterygium syndrome (cleft lip / palate, popliteal pterygium, genital and digital anomalies; typical facial and fingertip features of KS not seen)
- Branchiootorenal syndrome (similar ear shape without facial abnormalities of KS; hearing loss, renal abnormalities)
- Hardikar syndrome (cleft lip and cardiac abnormalities as in KS; preauricular dimples, pigmentary retinopathy and sclerosing cholangitis not found in KS)
- Down syndrome
- Fetal alcohol syndrome