Cryptic terminal deletion of chromosome 9q34: a novel cause of syndromic obesity in childhood?

besity is a symptom of diagnostic value in multiple congenital anomaly-mental retardation syndromes.While acquired non-specific weight gain related to drug intake or associated behavioural disorders occasionally occurs in the course of mental retardation, obesity is known to be a specific feature of several well defined conditions, including Bardet-Biedl syndrome, Prader-Willi syndrome, Cohen syndrome, fragile X syndrome, and several chromosomal anomalies.Yet a number of mentally retarded children with apparently early onset weight gain remain undiagnosed.Here, we report on a de novo deletion of chromosome 9q34 in two unrelated mentally retarded children with early onset obesity, distinctive facial features (brachycephaly, synophrys, anteverted nostrils, prognathism), sleep disturbances, and behavioural problems.FISH and microsatellite DNA analyses showed that the two children carried a similar small deletion (3 Mb) of the terminal long arm of chromosome 9 (del 9q34).We suggest therefore that the del 9q34 is a novel cause of syndromic obesity and mental retardation.Its association with distinctive facial features and behavioural problems should help in recognising this novel phenotype.Based on this observation, we suggest giving consideration to cryptic deletions of chromosome 9q34 in the diagnosis of unexplained obesity/ mental retardation syndromes CASE REPORTS Case 1 A boy was born to unrelated, healthy parents after a term pregnancy and normal delivery (birth weight 3200 g, length 50 cm, OFC 34.5 cm).He was hypotonic in the first months of life but no feeding difficulties were originally noted.Excessive weight gain with increased appetite and food seeking behaviour were noted at 30 months of age.At 5 years, his weight was 26 kg (>+3 SD), length 112 cm (+1 SD), and OFC 48 cm (-2 SD) and at 9 years his weight was 72 kg (>+ 6 SD), length 144 cm (+2 SD), and OFC 52.5 cm (-0.5 SD) (figs 1A-C and 2A).Distinctive facial features included brachycephaly, flat face, high forehead, synophrys, hypertelorism, anteverted nostrils, thin upper lip, prognathism, short hands, syndactyly of toes 2-3, (fig 1A-C), and abnormal genitalia (cryptorchidism and hypospadias).He had major developmental delay (head control at 11 months, walked unaided at 23 months, no speech at 9 years).Cerebral MRI showed partial frontal atrophy.Psychometric evaluation at 9 years showed performance at a 2 year old level (DQ=50).He was hyperactive, with a short attention span, intolerance to frustration, and sleep disturbances with repeated night awakenings.