Clinical Characteristics
Ocular Features
Reported facial dysmorphism features include periocular anomalies of ptosis, hypertelorism, down-slanting lid fissures, and epicanthal folds.
Systemic Features
The phenotype is somewhat variable. Intrauterine and postnatal growth retardation with hypotonia are common. Moderate to severe intellectual disability is usually present and speech may be severely delayed. The forehead is narrow, the nasal tip is broad, the nasal bridge is depressed, and the ears are low-set and posteriorly rotated. Small hands and sometimes joint laxity are commonly present. Cervical spine abnormalities including clefting, improper fusion, and segmentation anomalies are common.
Brain MRI may be normal but a small corpus callosum was present in some patients.
Genetics
Inheritance
Homozygous mutations in the CDK10 gene (16q24.3) are responsible for this disorder.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.