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At a glance

A severe polymalformative syndrome characterized by facial dysmorphism, absent clavicle, and extremity abnormalities. Often lethal within few months because of the failure to thrive and severe cardiorespiratory dysfunction.

Synonym

Cleidocranial Dysplasia with Micrognathia, Absent Thumbs, Distal Aphalangia Syndrome.

History

First described by E. Yunis and H. Varon in 1980.

Incidence

Unknown (fewer than 30 case reports worldwide).

Genetic inheritance

Autosomal recessive. Biallelic VAC14 or FIG4 mutation.

Pathophysiology

Disruption of phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] synthesis. Lipid phosphatase (FIG4) interacts with lipid kinase (PIKfyve) via adapter protein VAC14 all of which are essential for phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] synthesis.

Diagnosis

Suggested by prenatal ultrasonography, as well as by specific clinical features, including growth retardation prior to and after birth. Defective growth of the bones of the skull along with complete or partial absence of the shoulder blades (cleidocranial dysplasia) associated with characteristic facial features (severe micrognathia) and abnormalities of the fingers and toes complete the diagnosis.

Clinical aspects

Patients have marked psychomotor delay, postnatal failure to thrive, severe feeding problems, and respiratory difficulties. Clinical signs can involve head and neck (macrocrania with diastasis of cranial sutures; calvarial dysostosis; sparse scalp hair; hypoplastic facial bones; bitemporal indentations; small eyes; proptosis; low-set, dysplastic ears; anteverted nostrils; narrow and high-arched palate; severe micrognathia; occasional glossoptosis [moderate]; retracted and poorly delineated lips with diminished nasolabial distance), skeleton (absent clavicles; absent sternal ossification; pelvic dysplasia with hip dislocation; hypoplasia of thumbs; middle and distal aphalangia of the other fingers; agenesis of the first metatarsals; hypoplastic proximal phalanges of the big toes; delayed bone maturation; occasional pathological fractures; and nail hypoplasia), central nervous system (CNS) (arhinencephaly; absent corpus callosum; hypoplasia of the vermis; neuronal loss and vacuolation involving cerebral cortex; basal ganglia; cerebellar dentate nuclei and spinal anterior horns; hypertonia and hypotonia have also been reported), and heart (cardiomyopathy, tetralogy of Fallot). The majority of patients die in infancy as a result of severe failure to thrive and recurrent pneumonia. Survivors are severely delayed.

Precautions before anesthesia

A complete evaluation of the airway is necessary due to craniofacial abnormalities. The cardiac function must be assessed for the potential association of congenital heart defects with an echocardiogram most useful. Clinical evaluation of neurological function (consider CT, EEG). Blood examination must include a complete blood cell count because of frequent infections. Also, the hemoglobin, electrolytes, and glucose must be obtained. If the patient is on parenteral nutrition for failure to thrive, obtain albumin levels, liver enzymes, and bilirubin. Consider sedative premedication in older children with severe developmental delay.

Anesthetic considerations

There is no literature available about this ...

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