Chorioretinal Dysplasia-Microcephaly-Mental Retardation Syndrome

At a glance

A syndrome associated with microcephaly, mental deficiency, and chorioretinal dysplasia.

Synonyms

CDMMR Syndrome; Microcephaly with Chorioretinopathy; Microcephaly, Lymphedema, Chorioretinal Dysplasia Syndrome; MLCRD Syndrome; Lymphedema, Microcephaly, Chorioretinopathy Syndrome; Microcephaly with or without Chorioretinopathy, Lymphedema, Mental Retardation Syndrome; MCLMR Syndrome; Lymphedema and Retinal Folds with Microcephaly and Microphthalmos; Autosomal Dominant Microcephaly and Chorioretinopathy with or without Mental Retardation Syndrome.

Incidence

Unknown. Approximately 50 cases from about 30 families have been described.

Genetic inheritance

Transmission is autosomal dominant and in about 75% of cases caused by mutations in the KIF11 (kinesin family member 11) gene, which has been mapped to chromosome 10q23.33. Autosomal recessive inheritance has been reported for some cases and is caused by mutations in the TUBGCP6 (Tubulin-Gamma Complex-Associated Protein 6) gene located on chromosome 22q13.33. In about 40% of cases, the disorder is caused by de novo mutations. Penetrance is reduced and the phenotype very variable.

Diagnosis

Based on the clinical findings and molecular genetic testing can be used for confirmation.

Clinical aspects

As the name of the syndrome implies, affected patients suffer from primary microcephaly (ie, present at birth; in 86%), mild mental retardation (in 73% of patients), and (typically nonprogressive) chorioretinal dysplasia (in 59%; characterized by focal areas of lacunar atrophy and depigmentation of the choroid and retina), which are the most consistent findings. Lymphedema is present in 46% of patients, most often congenital and confined to the dorsa of both feet. Other central nervous anomalies may include lissencephaly, pachymicrogyria, cortical dysplasia, myelination delay, and white matter hypoplasia. Seizures have been described in a minority of patients. Additional ophthalmological features may include hypermetropia (in 24%) or myopia (in 14%), microphthalmia (in 8%), microcornea, and ocular pterygium. Cardiac lesions were described in 8% of patients and included congenital, thickened pulmonary valve, atrial septal defect, and patent foramen ovale. Typical facial features may include mild frontal bossing, prominent ears, occasional upslanting of the palpebral fissures, wide nose with a rounded tip, and long philtrum with thin upper lip. One family presented with polycystic kidney disease, which however was not considered to be associated with this syndrome.

Precautions before anesthesia

The renal function should be assessed if polycystic kidney disease is present (complete blood count, serum levels of electrolytes, creatinine, and urea). Anticonvulsant therapy should be continued until the morning of surgery and resumed as soon as possible postoperatively and given intravenously if oral intake is not possible. Developmental delay in combination with decreased vision may cause agitation and stress in the perioperative period, thus anxiolytic and sedative premedication and/or presence of a parent (or primary caregiver) for induction of anesthesia may be beneficial.

Anesthetic considerations