Larsen-Like Syndrome, Lethal Type

Chen et al. (1982) reported 2 isolated cases of a lethal, Larsen-like multiple joint dislocation syndrome. Death occurred shortly after birth with pulmonary insufficiency due to tracheomalacia and/or lung hypoplasia. Both patients showed abnormal dermal collagen bundles. Histochemical and electron microscopy showed abnormalities of cartilage matrix, collagen bundles of joint capsules and hyaline cartilage of the trachea. The authors characterized the defect as 'collagen fiber dysmaturity.' Clayton-Smith and Donnai (1988) reported a patient. Mostello et al. (1991) provided the first evidence of recessive inheritance of the lethal variant of Larsen syndrome. It is not certain, of course, that this disorder is produced by mutation in a gene distinct from that of the recessive form (245600) or, for that matter, that of the dominant form (150250) of Larsen syndrome. Mostello et al. (1991) diagnosed the disorder prenatally in a male fetus who by ultrasonography showed persistent genu recurvatum and probably other joint dislocations. The infant was delivered by Cesarean section at 37 weeks' gestation and died on the eighth day. A previously born male child, delivered at 39 weeks' gestation, had similar features (flat facies and multiple dislocations, especially anterior dislocation of the knees) and died at 24 hours of age. Both infants had severe pulmonary hypoplasia. Abnormal palmar creases and laryngotracheomalacia, features seen in patients with Larsen syndrome who survive, were observed in these lethal cases.

Yamaguchi et al. (1996) described neuropathologic evidence of a disturbance of neuroblast migration in a 3.5-year-old girl with a Larsen-like syndrome who manifested unusually severe neurologic signs that included intractable partial seizures, tetraplegia, and psychomotor retardation. The patient died of acute bronchiopneumonia. Neuropathologic findings included bilateral perisylvian cortical dysgenesis, protrusions of the brain parenchyma into the subarachnoid space (brain warts), abnormal arrangement of neurons in the inferior olive, and dilatation of the lateral ventricles with multiple glial nodules. The authors speculated that the brain dysplasia, which had been described in previous Laresen-like syndrome cases (e.g., Clayton-Smith and Donnai, 1988, Chen et al. (1982)), may have been the result of systemic hypoxic-ischemic insults during the second half of gestation, but they did not rule out genetic factors.