Genetic and Myhre syndrome

Myhre syndrome

First described in 1981 by Myhre, Ruvalcaba and Graham, the Myhre syndrome is characterized by short stature, brachydactyly, facial dysmorphism (short palpebral fissures, prognathism, short philtrum), thick skin, generalized muscle hypertrophy and restricted joint mobility.

Myhre syndrome is a well-defined disorder characterized by preand postnatal short stature, brachydactyly, facial dysmorphism(short palpebral fissures, maxillary hypoplasia, prognathism and short philtrum), thick skin, generalized muscle hypertrophy and restricted joint mobility1. Deafness that is of mixed conductive and sensory types is consistently observed in older individuals with this syndrome. Other features include developmental delay with mental retardation and/or behavioral disturbance, cardiac defects, cryptorchidism and bone anomalies. Skeletal manifestations include thickened calvarium, cone-shaped epiphyses, shortened tubular bones, hypoplastic iliac wings, broad ribs and large vertebrae with short and large pedicles.

Genetic and Myhre syndrome

Mutations in the SMAD4 gene cause Myhre syndrome. The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. This signaling pathway, called the transforming growth factor beta (TGF-β) pathway, allows the environment outside the cell to affect how the cell produces other proteins. As part of this pathway, the SMAD4 protein interacts with other proteins to control the activity of particular genes. These genes influence many areas of development. Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.