Illum Syndrome

Clinical Features

Illum et al. (1988) reported 3 sibs and Schrander-Stumpel et al. (1991) reported 3 unrelated patients with a lethal syndrome of arthrogryposis multiplex congenita with whistling face. The patients of Illum et al. (1988) were 2 sisters and a brother who died at ages 2 days, 3 days, and 3 months, respectively. Autopsy showed extensive deposits of calcium compounds in the central nervous system and in skeletal muscle. In addition to congenital contractures of several joints, the patients had signs of dysfunction of the central nervous system and the autonomic nervous system with excessive salivation, temperature instability, apnea, and bradycardia. Schrander-Stumpel et al. (1991) labeled the disorder as fetal hypokinesia sequence, an obviously heterogeneous category, and pointed out that their patients also had the Pierre Robin sequence. One of their patients died at age 12 years, a second at the age of 6 months, and the third, born in late 1986, was apparently still living at the time of report. They reported that maternal myotonic dystrophy (160900) was excluded in all 3 cases. There was no parental consanguinity in any of these cases. The presumed autosomal recessive inheritance as well as the phenotypic differences excludes the Freeman-Sheldon form of whistling face syndrome (193700). A recessive form of whistling face syndrome has been proposed; see 277720.

Di Rocco et al. (1992) reported a boy with blepharophimosis, whistling face, small mouth, high palate, distal arthrogryposis, myoclonic epileptic fits and 'absent' psychic development. The child died at the age of 6 months.

Chong et al. (2015) suggested that the patients reported by Schrander-Stumpel et al. (1991) and Di Rocco et al. (1992) had CLIFAHDD (616266) rather than Illum syndrome. They suspected that these patients likely had mutations in the NALCN gene (611549).