Clinical Characteristics

Growth parameters
Growth retardation is a key feature of the disease and may be observed before birth during ultrasound screening. At last examination, reported patients have a mean height of -3 SD (range: -1.3 to -4.7 SD), a mean weight of -3.1 SD (range: -0.2 to -4.7 SD), and a mean occipitofrontal circumference of -2.2 SD (range: – 4.6 to + 3 SD). A single patient with OFC at + 3 SD had severe hydrocephalus.

Developmental delay and intellectual disability
All patients displayed developmental delay. Language is more affected than motor development. Mean age of sitting was 19 months (range: 11–30 months), mean age of walking without assistance was 33 months (range: 22–48 months). A pronounced language delay was noted (no language or two-word combinations with no sentences). The estimated degree of intellectual disability was moderate to severe. All affected patients had a learning disorder.

Spine malformations
Spine anomalies are a hallmark of the syndrome. Affected patients notably displayed cervical spine malformations including clefting of the posterior arch of the atlas (C1) and partial fusion of C2 and C3 cervical vertebral bodies.

Patients share recognizable dysmorphic facial features: a triangular face with a small pointed chin, low-set and posteriorly rotated ears, a wide nasal base, a long philtrum, a mild ptosis, telecanthus  and epicanthal folds.

Unstable broad-based gait, muscular weakness, joint hyperlaxity, pes planus, sacral dimple, hypothyroidism, recurrent infections, congenital heart disease, corpus callosum hypoplasia, bilateral sensorineural deafness and retinitis pigmentosa.