Is Hardikar syndrome distinct from Kabuki (Niikawa-Kuroki) syndrome?

To the Editor : Kabuki syndrome (OMIM 147920), also known as Niikawa–Kuroki syndrome (NKS), is characterized by distinctive facial features, skeletal anomalies, dermatoglyphic abnormalities, mental retardation, and growth deficiency (1, 2). Recently, mutations in the MLL2 gene were identified as the genetic cause of NKS (3). Hardikar syndrome (HS; OMIM 612726) is a multiple congenital anomalies syndrome with unknown aetiology, in which cleft lip and palate, patchy pigmentary retinopathy (cat’s paw) and obstructive liver disease are associated (4–6). We observed a girl with typical facial features of NKS who also developed a hepatoblastoma and retinal pigmentation anomaly ‘cat’s paw’ type. By comparing our patient’s phenotype with the patients with HS described to date, we focused on the overlapping features of the two syndromes. The proband was the only child of healthy nonconsanguineous parents. A previous early spontaneous abortion was reported. At the child’s birth, the mother and the father were 33 and 41 years old, respectively. Ultrasound examination during pregnancy revealed polyhydramnios and right hydronephrosis. At birth, retinal haemorrhages were noted. Neonatal period was characterized by marked hypotonia, jaundice treated with phototherapy and feeding difficulties. At the fifth week of age, a right ureteroplasty was performed. At 9 months, a hepatoblastoma was diagnosed and treated by surgical resection and chemotherapy. Motor and cognitive milestones were delayed. At 7 years of age, neurological evaluations indicated moderate mental retardation, perceptive difficulties and dyspraxia, and bilateral neurosensorial hypoacusia of mild degree. The ophthalmological examination showed pigmentary retinopathy with patchy pattern (cat’s paw). Premature thelarche was present. Menarche occurred at 10 years of age. When we examined the patient at 10 years 4 months of age, height was 137 cm, weight 39 kg (body mass index 20.8) and head circumference 54 cm. She showed the typical facial features of NKS (Fig. 1), generalized hypotonia, kyphosis, persistence of fingerpads, bilateral clinodactyly of the fifth hand fingers. She also presented high-arched palate, teeth hypoplasia and agenesis of the lower and upper lateral incisors. Karyotype and array-CGH revealed no abnormalities. Direct sequencing of the MLL2 gene showed a heterozygous c.11119C>T variant in