Typical features are craniostenosis,
microcephaly, large occiput, mental retardation, seizures, external
ophthalmoplegia, myopathic stiff facies, low-set and large, malrotated ears,
open mouth, microgenia, abnormal temporomandibular joints (anomaly of the
processus condylaris and mandibulares), high arched palate with cleft, and
velopharyngeal insufficiency are common findings. Swallowing difficulties
(absent gag reflex) and generalized myopathic hypotonia are typical.
Laryngomalacia, recurrent pneumonias, and pectus excavatum have been
described in the majority of patients. The most characteristic sign is
flexion and adduction of the thumbs with arthrogryposis of elbows, wrists,
and knees. Respiratory insufficiency is mainly caused by the generalized
myopathic hypotonia and the main reason for the poor prognosis with death in
early infancy (only one patient has survived the first year of life). Muscle
biopsy reveals unspecific signs of congenital myopathy (i.e., wide variation
in the diameter of muscle fibers, normal distribution of type I and II
fibers, increased number of centrally located nuclei, increased interstitial
tissue, lack of signs of denervation).