The proband is a 12-months-old boy with typical facial dysmorphism, hearing defect and bony abnormality (Table 1). He was born after a normal pregnancy and delivered with birth weight of 2.9 kg (10th percentile) and birth length of 45 cm (3rd percentile) at 38 weeks, compared with the WHO Child Growth Standards in 2006. The facial appearance presents bulging forehead, prominent ears, widely spaced eyes, down slanted palpebral fissures, short nose with broad columella, thick alae nasi and septum, thick and everted underlip (Figures 1A,B). The deciduous teeth were erupted at 8 months old (not delayed) (Figure 1C). The hands are short, fleshy, and with remarkably hyperextensible fingers that taper from wide to narrow with small terminal phalanges and nails (Figures 1D, 2D). But there was no deformity of his foramen magnum or spine column (Figures 2B,C). The weight at 12 months is 8.2 kg and height is 68.2 cm (<-3.17 z score, WHO). The bone metabolism and IGF-1α is disturbance (Vit D 45.2 nmol/L, IGF-1α < 25 ng/mL). He started sitting alone at 9 months and couldn't stand unaided until 12 months of age. At 12 months of age, his intelligence quotient (IQ) was 56 according to the Gesell Developmental Schedules. He had difficulty remaining seated or concentrating during task completion. His auditory threshold of auditory brainstem response (ABR) is >85 db and is diagnosed as a hearing disorder. The magnetic resonance imaging (MRI) showed the dilation of bilateral ventricles and less cerebral white matter (Figure 2A).
A side view of the patient's face (B), prominent ears, widely spaced eyes, down slanted palpebral fissures, short nose with broad columella, thick alae nasi and septum, thick and everted underlip (A,C). (D) The hands are short and with puffy tapered finger, small terminal phalanges, and nails.
Sanger sequencing validation for the mutation of RPS6KA3 in the proband at chromosome Xp22. A mutation of c.2185 C > T was detected in imprinting control region from allele 290–300, which was not detected in proband's mother.
7. 骨代谢紊乱：维生素D 45.2 nmol/L
8. IGF-LC<25 ng/ml
The typical phenotype of Coffin–Lowry syndrome of proband.
1 . Typical facial dysmorphism : bulging forehead , prominent ears , widely spaced eyes , down slanted palpebral fissures , short nose , everted underlip
2 . Hearing defect : 85 db ( both ears )
3 . Hyperextensible fingers that taper from wide to narrow with small terminal phalanges and nails
4 . Short stature : 68.2 cm at 1 year old
5 . Mental retardation : IQ was 56
6 . Hypoevolutism in motor development
7 . Bone metabolism disturbance : Vit D 45.2 nmoll
The present study is the first to report a Chinese case of Coffin–Lowry syndrome with mutation of RPS6KA3, as well as distinctly growth retardation, multiple facial abnormalities, intellectual and motor disabilities. We speculate that the application of growth hormone analogs may increase the incidence and invasiveness of cancers as well as the risk of spine malformation. If its efficacy and safety are not confirmed, the application of growth hormone analogs on patients of CLS should be especially cautiously considered. Long-term studies with relevant outcome will be essential in the future clinical research.