Fryns Macrocephaly

Clinical Features

Fryns et al. (1994) described a brother and sister, aged 8 and 15 years, respectively, with a subtype of complicated spastic paraplegia distinguished by the presence of macrocephaly and distinctive craniofacial appearance (broad and high forehead, deeply set eyes, short upper lip, prominent upper incisors, and everted lower lip).

A third patient who appeared to have this disorder was reported by Moog et al. (1998). Severe psychomotor retardation was present from birth. She was initially described as having a flaccid paresis, but by the age of 15 she developed spastic paraplegia, and later increased tone of the upper limbs as well. Seizures developed in adulthood. She developed progressive kyphoscoliosis and became bedridden. Her head circumference at 30 years of age was 58 cm (98th centile). Her craniofacial appearance showed a rectangular shape to the face, slight coarseness of features, broad forehead, prominent supraorbital ridges, deep-set eyes, and thick hair with a low posterior hairline. Published pictures showed a thin upper lip and short philtrum (Williams and Josephson, 2003). Neuroimaging showed cerebral atrophy.

Williams and Josephson (2003) presented an adult female patient with macrocephaly, mental retardation, seizures, spastic paraplegia and distinct craniofacial appearance. The patient manifested a striking resemblance to patient 1 of Fryns et al. (1994). Given that the spasticity in their patient was slowly progressive, the authors contacted Fryns, who confirmed that the spasticity in his 2 patients was slowly progressive also. Additionally, macrocephaly in his patients was not present early on, but was progressive as well.

Inheritance

Based on the occurrence of this disorder in sibs, Fryns et al. (1994) suggested autosomal recessive inheritance.