Pathogenic variants in the LIFR gene cause a multisystem disorder.
Prenatal manifestations:
• Oligohydramnios
• Intrauterine growth retardation
• Reduced fetal movements
• Short bowed long bones.
Neonatal period:
• Dysmorphic features: short nose with wide base, pursed mouth, midface hypoplasia, and hypotonia.
• Radiological findings: bowing of the long bones, internal cortical thickening at the concavity of the bend, and wide metaphyses with irregular striation.
• High risk of death due to respiratory distress, swallowing difficulties and temperature instability.
Childhood survivors (beyond the first two years of life):
Common features:
• Severe and progressive shortening and bowing of the limbs.
• Characteristic radiological pattern: dyaphiseal/metaphyseal undertubulation and abnormal trabecular pattern metaphyses.
• Facial dysmorphic features: dolichocephalic cranium, midfacial hypoplasia, short and wide nose, anteverted nostrils, a square jaw and abnormalities of the lips.
• Temperature dysregulation (hyperthermic episodes and/or paradoxical sweating) as part of dysautonomia, usually present already in the neonatal period.
• Poorly enamelled teeth with early dental loss.
• Most of them also have swallowing problems (93%) and respiratory distress (80%).
Most of them have also the following features (40-80%):
• Short metacarpal and metatarsal bones
• Trabeculated metaphyses of phalanges
• Wide metaphyses
• Destruction of femoral heads, coxa vara
• Scoliosis
• Osteopenia.
• Brachydactyly
• Talipes valgus/equinovarus
• Enlarged joints
• Contractures and camptodactyly.
• Smooth tongue, reduced pain sensation, absent corneal reflex, as part of dysautonomia.
• Hypotonia
• Recurrent infections
Secondary and frequent clinical manifestations:
• Short stature
• Prenatal IUGR
• Motor delay
• Secondary to dysautonomia: dehydration, skin and tongue wounds, and less frequently eye infections and corneal scarring.
• Recurrent fractures
Less frequent manifestations (<40%):
• Facial features: Frontal bossing, micrognathia, short neck.
• Radiological features: Widening of the ribs, displastic hips.
• Reduced patellar reflexes, as part of dysautonomia.
Prognosis
SWS was initially considered a lethal condition during the first year of life, mainly due to respiratory compromise and/or temperature instability. However, in recent years a number of individuals surviving beyond the first 2 years of life that have been reported.
Long term prognosis is not well known, but maybe be affected by skeletal and dysautonomic manifestations.
LIFR