Agenesis Of The Corpus Callosum And Congenital Lymphedema

Clinical Features

O'Driscoll et al. (2010) reported 2 patients, related as double first cousins, with a unique combination of developmental delay, agenesis of the corpus callosum, and congenital lymphedema. Both were born by emergency cesarean and had difficulty in the newborn period. The first patient, a girl, was born at 31 weeks' gestation due to preeclampsia and suspected placental insufficiency. She had severe intrauterine growth retardation and microcephaly at birth. The second patient, a boy, was born at 35 weeks' gestation for reduced fetal movements and oligohydramnios. Both patients had a sacral dimple at birth with no associated abnormalities and pulmonary hypertension in the newborn period. Both had lymphedema at birth, in the lower limbs in the girl and in all 4 limbs in the boy. The lymphedema had resolved or was resolving by age 2 years. At age 3, the girl showed significant developmental delay, with inability to walk independently and few single words. The boy also had global developmental delay but could walk independently and speak a few words. Both patients had mild facial dysmorphism, with dolichocephaly, wide anterior fontanel, short palpebral fissures, epicanthal folds, low-set and posteriorly rotated ears, upturned nose, long philtrum, thin upper lip, and high-arched palate. Brain MRI of both patients showed severe partial or almost complete agenesis of the corpus callosum, respectively, mild hippocampal dysplasia, basal ganglia cysts, and laterally displaced lateral ventricles. Other features included a cheerful personality and gastroesophageal reflux disease. O'Driscoll et al. (2010) noted some phenotypic overlap with Hennekam syndrome (235510) and FG syndrome (305450), but concluded that the patients did not fit into either category, suggesting a new distinct disorder.

Inheritance

As the affected boy and girl reported by O'Driscoll et al. (2010) were related as double first cousins, the inheritance pattern was most consistent with autosomal recessive.