Is short stature in Myhre syndrome related to growth hormone neurosecretory dysfunction?

Myhre syndrome (MS) is a very rare condition described in 1980 characterised by facial dysmorphism, brachydactyly, musclehypertrophy, decreased joint mobility, hearing loss, mental retardation, and short stature. The pattern of inheritance and the genemutations of MS are unknown. All reported patients were sporadic and paternal age was increased in half of the cases, suggestingdominant new mutations. We present a case with clinical findings typical for MS whose short stature might be partially related to GHneuro-secretory dysfunction. M.U., male, karyotype 46,XY, born at 37 weeks of gestation (BW 2.225 kg), was admitted to geneticevaluation for dysmorphic features. He had short palpebral fissures, maxillary hypoplasia, prognathism, small mouth, brachydactyly,muscle hypertrophy, decreased joint mobility, hearing loss, mental retardation and short stature. X-rays showed a thickened calvarium,broad ribs, hypoplastic iliac wings, large vertebral pedicles. The phenotype was very consistent with the diagnosis of MS. An accuratedifferential diagnosis ruled out similar dysmorphic conditions (Geleophysic dysplasia, acromicric dysplasia, OSMED, GOMBO, Moore-Federman syndromes). At 7.6 years of age because of a progressive impairment of height (cm 108, centile 0.2, -2.89 SDS) anendocrinological evaluation was performed. The hypothalamic-pituitary-IGF-1 axis (HP-IGF-1 axis) was investigated measuring baselineIGF-1 levels and spontaneous 24-hour GH profile by multiple sampling. The low IGF-1 levels (135 ng/ml) and the value of 24-hour GHprofile (2.13 ng/ml) were consistent with the condition of neurosecretory dysfunction. Disturbances of HP-IGF-1 axis were alreadyreported in subjects with MS but, to our knowledge, this is the first case of MS in whom a GH neurosecretory dysfunction has beendetected. Even if in this syndrome short stature is largely attributable to skeletal dysplasia, the impaired GH secretion may play a role inthe alteration of growth, suggesting the possibility that a GH therapy can improve the final height of these patients.