ESPE Abstracts

Introduction: Luscan-Lumish syndrome (LLS) is a postnatal overgrowth syndrome characterized by macrocephaly, mental retardation, seizures, postnatal overgrowth, and developmental delay, caused by a heterozygous mutation in the SETD2 gene on chromosome 3p21, which exhibits autosomal dominant inheritance.

Case Report: A ten-year-old girl presented with menarche. She was born to healthy non-consanguineous parents at 37 weeks, 3100g (0.6SD), 56cm (4.5SD) and head circumference 38cm (3.78SD). She had a voracious appetite since infancy, walked at 18 months, spoke at two years, and her motor development lagged behind her peers. However, after the age of three, her growth increased compared to her peers. She was having tantrums. At admission, physical examination showed weight 59.2kg (+2.76SD), height 157.6cm (3.04SD), mid-parental height 163.8cm (0.11SD), body amss index 23.8 (+1.91 SD) and macrocephaly, short neck, long and dull face, prominent forehead, cubitus valgus, abdominal obesity, cafe-au-lait spot and scoliosis. She was Tanner stage 5, and bone age was two years advanced. Cranial and pituitary imaging were normal. Insulin-like growth factor levels were normal and GnRH analogue treatment was started with the diagnosis of central precocious puberty. On oral glucose tolerance test, impaired glucose tolerance and hyperinsulinism were detected while growth hormone was suppressed, and metformin was started. Mccune-Albright syndrome was excluded as no mutation was found in the GNAS gene. Luscan Lumish Syndrome was diagnosed after detection of the c.1322G>C (p.Arg441Pro) heterozygous missense novel pathogenic variant in the SETD2 gene on whole-exome sequencing (WES). On child psychiatry examination, it was reported that intellectual development was normal, but she had behavioral problems.

Discussion and Conclusion: LLS is characterized by overgrowth, mental retardation, speech delay, and behavioral problems; obesity, advanced bone age, autism, and seizures occur with variable frequencies. While seizures, autism, and mental retardation are observed in frameshift or nonsense mutations in SETD2, the mild clinical presentation in this case may be explained by the missense mutation. Rapid growth in children may be perceived as “healthy growth” by parents and may cause late presentation. When evaluating the pathological cause of tall stature, even if there is precocious puberty, in the presence of dysmorphic findings, genetic diagnosis and WES may be advisable, for optimal diagnosis and subsequent management of patients.