An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation

Abstract

Cerebral palsy (CP) is defined as any nonprogressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Symptoms become apparent during the first year of life. Genetic forms of CP account for about 2% in European populations but are thought to cause a substantial proportion in consanguineous families. We have identified a large consanguineous family from Oman with spastic diplegia, microcephaly, and mental retardation. Additional manifestations include hyperreflexia, clumsiness, unstable gait, drooling, and dysarthria. There was phenotypic variability among different individuals, but spastic diplegia, microcephaly, and mental retardation were three constant traits present in all affected individuals.

Figure 1

Pedigree structure of the family. There is a high frequency of consanguineous marriage in this family. Patients described in this study are numbered. Squares and circles indicate males and females, respectively. Affected individuals are shown as filled symbols. The parents of patients are not listed on the order of birth for the sake of viewing.

Figure 2

Craniofacial morphologies and MRI of the patients with spastic CP. Craniofacial morphologies of Patient 4 (A and A′), 9 (B and B′), 5 (C), and 6 (D) showing microcephaly, brachycephaly, and low anterior and temporal hairlines. (E) Brain MRI of Patient 3. Conventional spin-echo MR imaging of the brain was performed in multiple planes. This T2-weighted axial image demonstrates the presence of a normal gyral pattern, normal white matter signal, normal basal ganglia, and normal ventricular morphology and size. (F) Brain MRI of Patient 5. Conventional spin-echo MR imaging of the brain was performed in multiple planes. This T1-weighted parasagittal image demonstrates a craniofacial disproportion suggestive of microcephaly. No other abnormalities of brain anatomy are seen.