Background: Klinefelter syndrome is the most common sex chromosome disorder (prevalence: 1/600 newborn males), characterized by at least one extra X chromosome. If the diagnosis is not made prenatally, the disorder can remain unknown until pubertal or adult age. Kabuki syndrome, instead, is a rare, dysmorphic syndrome (1:32 000 newborn) characterized by distinctive facial features, multiple anomalies, and mental retardation. About 5080% of cases are due to de novo or autosomal dominant MLL2 or KMT2B gene mutation (point mutation, deletion, duplication) located on 12q13.12; less frequently, and deletions or point mutations involving the KDM6A gene, located on Xp11.3, are implicated.
Objective and hypotheses: We report the case of a boy affected by both Klinefelter and Kabuki syndromes.
Method: Our patient was born at 38 weeks of gestational age by cesarean section; he underwent neonatal resuscitation with O2-administration. Weight and length at birth were at the 50th percentile, head circumference at the 35th Progressive postnatal weight growth retardation (associated with normal height velocity) and recurrent aspiration pneumonia needed enteral nutrition by percutaneous gastrostomy. Microcephaly, distinctive facial appearance (big eyes with long palpebral fissures, long cilia, anteverted nostrils, extroverted lower lip with pits, cupped ears, and operated cleft palate), persistence of fetal fingertip pads, eczema, hypotonia in infancy, congenital heart disease (atrial septal defect), joint and cutaneous laxity, and mild development delay became evident. Genitalia were normal at clinical examination; abdominal ultrasound showed normal kidneys and liver.
Results: Karyotype was 47,XXY, while sequence analysis of the Kabuki genes showed a heterozygous c.721delC de novo mutation (L241CfsX260) of the MLL2 gene.
Conclusion: An association between Klinefelter and Kabuki syndromes has not been described yet. Probably these two genetic conditions casually coexist in our patient, due to the relatively high prevalence of the first.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology