We describe two very rare genetic diseases characterized by particular physical features and deviation from normal growth. The first patient, CM, was admitted for delayed growth (113 cm at 8 years of age, -3 S.D.). The child had short lower arms with small hands and clinodactyly of the fifth finger. He had round widely spaced eyes with long eyelashes, a flat profile and prominent forehead, short upturned nose, misaligned teeth and gum hypertrophy. We diagnosed a rare (incidence of 1/500 000) autosomal dominant foetal face Robinow syndrome. The recessive syndrome is more severe and is related to mutations of a tyrosine kinase gene located on chromosome 9q22. The mutation for the dominant form is currently unknown. Our patient responded poorly to GH stimulation tests, so GH therapy was initiated. The second patient, IU, a 31 year old adult with a height of 220 cm, large extremities, horse-like face and severe mental handicap, was admitted with initial suspicion of acromegalic gigantism. The patients weight at birth was of 4500 g and he was the tallest of his generation from an early age. Clinical examination revealed a large mouth, macroglossy with incomplete mouth occlusion, defects in dental implantation with supernumerary teeth and sharp canines (bulldog teeth), and a short nail bed. The GH/IGF-I axis and the pituitary gland visualised by MRI were normal. Interestingly, the patient has a younger brother with comparable, although less dysmorphic features, with a height of only 195 cm and a normal intellect. The patient was diagnosed with Simpson-Golabi-Behmel (SGB) syndrome, a rare X-linked disease whereby glypican-3 is inactivated, leading to enhanced activation of various growth factors. The SGB syndrome is a true rarity only 130 cases described until 2008. Perturbed growth process added to mysterious clinical features could be the diagnostic tip for rare diseases with genetic background.
24 - 28 Apr 2010
European Society of Endocrinology