A severe lethal syndrome combining disproportionately
large head with peculiar facies and bilateral talipes equinovarus.
Approximately 10 cases have been
described. Most likely autosomal recessive transmission. Parental
consanguinity was observed in some, but not all cases.
This complex polymalformative syndrome with
severe intrauterine growth retardation may involve the head and neck
(macrocephaly with disproportionate small face, deficient mineralization of
the calvaria [or even absence of frontal, parietal, and occipital bones],
agenesis of the corpus callosum, absence of the cingulate gyrus,
increased ventricular size, severe hypertelorism, low-set and posteriorly
rotated ears with hypoplasia of the helix, depressed nasal bridge, wide and
upturned nares, lateral cleft lip, cleft palate, or even absence of hard and
soft palate, severe micrognathia/retrognathia, short neck) and the skeleton
(absent cervical vertebrae, absent or abnormal clavicles, hypoplastic
scapulae, 11 rib pairs, large and small joint contractures, club foot,
hypoplastic distal middle phalanges, soft tissue syndactyly of fingers and
toes). Either hirsutism or absence of scalp and body hair, esophageal
stenosis, redundant bowel loops, hypoplastic external genitalia,
hypogonadism, and cryptorchidism have been described, but are not constant
features. Cardiovascular anomalies are inconstant and may consist of thin
myocardium and thick-walled ascending aorta and pulmonary artery.
Intrauterine death or death in early infancy is common.
It is unlikely that these patients
present for anesthesia. Difficult tracheal intubation should be anticipated,
and maintenance of spontaneous ventilation is recommended until the airway
has been secured. Subclavian central venous access should be avoided because
of clavicular malformations. Careful intraoperative positioning is required,
and the brain must be protected from external pressure in the absence of
Fetal Aminopterin Syndrome: A polymalformative teratogenic syndrome
characterized by short stature, skull anomalies, hydrocephalus, and facial
anomalies (abnormal auricles, hypertelorism, micrognathia, cleft palate).
Barnicoat AJ, Seller MJ, Bennett CP: Fetus with features of Crane-Heise
syndrome and aminopterin syndrome sine aminopterin (ASSAS). Clin Dysmorphol
Crane JP, Heise RL: New syndrome in three affected siblings. Pediatrics
Zand DJ, Carpentieri D, Huff D, et al: Crane-Heise syndrome: A second
familial case report with elaboration of phenotype. Am J Med Genet 118A:223, 2003.