Acrocephalopolysyndactyly Type II: Carpenter Syndrome (CS)

At a glance

Craniosynostosis, acrocephaly, peculiar facies with midface and mandibular hypoplasia, high-arched palate, short stature, short neck, and syndactyly. This syndrome has cardiac malformations.

History

First described in 1901 by the British physician George Carpenter (1859–1910).

Incidence and genetic inheritance

The incidence is estimated at 1:1,000,000 live births with approximately 100 cases reported to date. Inheritance is autosomal-recessive. CS Type I is caused by homozygous mutations in the RAB23 gene located on chromosome 6p12.1-q12. Rab proteins are guanosine triphosphatases mainly involved in the intracellular regulation, trafficking, and recycling of membrane-associated proteins. In CS Type II, a less frequent subtype of CS, the mutation affects the MEGF8 (Multiple epidermal growth factor-like domains 8) gene, which has been mapped to chromosome 19q13.2. CS Type II exhibits wide clinical overlap with CS Type I, but is frequently associated with abnormal lateralization of the body, ie, complete situs inversus, dextrocardia, or transposition of the great arteries, suggesting that MEGF8 plays an important role in left-right patterning.

Diagnosis

Based on the typical clinical findings.

Clinical aspects

Most patients are born with an increased birth weight and have a tendency of obesity later on in life. The craniofacial features of CS include craniosynostosis affecting (in order of frequency affected) the sagittal, metopic, coronal, or lambdoid cranial sutures, often resulting in brachy- and/or acrocephaly. Hypoplastic anterior cranial fossa, shallow supraorbital ridges, inferiorly displaced eyes, hypertelorism, microcornea, corneal clouding and telecanthus, depressed nasal bridge with a broad and upturned nose, hypoplastic maxilla, high-arched palate, micrognathia, microstomia, and external ear malformations with conductive and/or sensorineural hearing loss are all common findings. While some patients have normal intelligence, the majority of CS patients shows mild-to-moderate mental delay with pathological findings on neuroimaging (CT or MRI), including agenesis of the corpus callosum, cerebellar hypoplasia, agyria, enlarged lateral ventricles, dilatation of the Sylvian aqueduct, and pseudopapilledema. Increased intracranial pressure (ICP) and hydrocephalus requiring a ventriculoperitoneal shunt occurs in about 20% of these patients. Oro-dental anomalies are common and may include broad alveolar ridges, dental crowding or anodontia, and delayed extrusion of deciduous teeth. Beside the typical skeletal abnormalities of brachy-, (cutaneous) syn-, and polydactyly or mesophalangeal agenesis of hands and feet, other bony deformities are common (eg, scoliosis, spina bifida occulta, coxa vara, genua valga). Up to half of CS patients have a congenital cardiac lesion, such as atrial or ventricular septal defects, Tetralogy of Fallot, transposition of the great arteries, pulmonary valve stenosis, or patent ductus arteriosus. Omphalocele, umbilical hernia, hydroureter, and hydronephrosis have also been described. The majority of male patients have cryptorchidism and/or hypoplastic genitalia.

Precautions before anesthesia

Evaluate the head and neck anatomy in consideration of airway management (reduced size of naso- and oropharynx, maxilla, and mandible and anomalies ...