Steinfeld Syndrome

Clinical Features

Steinfeld (1982) reported the case of a female infant with multiple congenital anomalies including holoprosencephaly, bilateral hypoplasia of radius and ulna, absent thumbs, midline cleft lip and palate with absent philtrum, congenital heart defect, unilateral renal dysplasia, and absent gallbladder. A sister died of similar malformations including phocomelia, absent gallbladder, ectopic kidney, and congenital heart defect. The father had short forearms and rudimentary thumbs. His sister died in infancy with severely malformed limbs; his father and a brother lacked thumbs. The familial pattern was considered consistent with autosomal dominant inheritance of a trait involving, at the very least, limb defects.

Nothen et al. (1993) reported a second family with Steinfeld syndrome with dominant inheritance and variable expression. The proband was a male fetus with alobar holoprosencephaly, microphthalmia, midline cleft lip and palate, absent nose, dysplastic ears, radial defects, pentalogy of Fallot, unilateral renal aplasia, absent gallbladder, vertebral anomalies, and absent ribs. The father had a cleft palate, bilateral colobomas of the iris and retina, a bifid uvula, vertebral anomalies, and unilateral congenital hearing loss. His sister had a cleft lip.

Stevens (2010) reported a 23-week-old male fetus with severe congenital anomalies consistent with Steinfeld syndrome. Prenatal ultrasound revealed alobar holoprosencephaly, abdominal situs inversus, abnormal cardiac valves, and severe limb defects. On postmortem exam, the fetus was noted to have small eyes, bilateral cleft lip and palate, low set malformed ears with absent canals, and micrognathia. The forearms were absent with 3 digits attached at each elbow. The legs were absent, and the right foot with 4 toes was attached to the right side of the pelvis; a single digit was attached to the left side of the pelvis. There was a normal penis, absent scrotum, and patent anus. Radiographs showed absence of the radii, ulnas, femora, tibias, fibulas, and the left iliac crest. There were only 2 metacarpals in each hand. There was also a cleft in the upper lumbar spine seen on lateral view. Chromosome analysis and comparative genomic hybridization studies were normal, and sequence analysis of known holoprosencephaly-associated genes did not identify mutations.

Inheritance

The families reported by Steinfeld (1982) and Nothen et al. (1993) had at least 1 instance of male-to-male transmission. Autosomal dominant inheritance inheritance with variable expressivity seems likely.