Syndromic growth disorders

Abstract

Short stature (SS) is defined as height less than the third percentile or below –2 standard deviation score (SDS) with reference to chronological age according to standard growth curves. Children are born small for gestational age (SGA) when their birth height and/or birth weight are below or equal to –2 SDS using standards such as Usher and McLean. In patients presenting with SS associated with abnormal physical features, malformations, or delayed development, a syndromic growth disorder should be considered. Whilst individually rare, there are many syndromes with short stature as a component—in the London Dysmorphology Database (Winter and Baraitser), there are 873 such syndromes, 175 of which are of prenatal onset. In these patients, malformations and/or sensorineural abnormalities should be systematically screened by complementary exams (skeletal X-rays, cardiac and abdominal ultrasound, complete eye and hearing evaluations). In some cases, these abnormalities could help in making the diagnosis (e.g. pulmonary stenosis suggestive of Noonan’s syndrome). Different chromosome disorders may present with SS. For this reason, chromosome studies, preferably high-resolution analysis, should be performed to search for chromosome abnormalities in these children. Specific gene analysis may be requested when a specific syndrome is suspected. In these syndromes, growth failure may be due to a wide variety of mechanisms, including growth hormone deficiency (GHD), growth hormone resistance (Laron syndrome, bone dysplasia) or in combination with nutritional issues with, in many, the underlying mechanisms still being unknown. A complete evaluation of growth hormone/IGF-1 axis is necessary in these children. There are many classifications of short stature, each with specific advantages and disadvantages. Indeed, syndromes with SS could be classified according to clinical presentation and in particular auxological and anthropometrical parameters (SS with normal prenatal growth, SS with intrauterine growth retardation, SS with obesity), or to pathophysiology (GHD or growth hormone insensitivity, bone disorders and idiopathic SS). Here, a classification based on clinical presentation is used. Those syndromes with SS that are most common and are often followed by paediatric endocrinologists namely Silver–Russell, Noonan’s, Turner’s and Prader–Willi syndromes will be reviewed, as well as some rarer syndromes.