Stuve-Wiedemann syndrome

Alternate names

STWS; Schwartz-Jampel syndrome type 2; SJS2; Schwartz-Jampel syndrome neonatal; Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome; Neonatal Schwartz-Jampel syndrome type 2

Definition

Stuve-Wiedemann syndrome (STWS) is a congenital skeletal (bone) dysplasia characterized by small stature, bowing of the long bones, and other skeletal anomalies.

Summary

• It is a severe condition characterized by bone abnormalities and dysfunction of the autonomic nervous system, which controls involuntary body processes such as the regulation of breathing rate and body temperature.
• Another condition once known as Schwartz-Jampel syndrome type 2 is now considered to be part of Stüve-Wiedemann syndrome. Researchers have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used.

Epidemiology

Stüve-Wiedemann syndrome is a rare condition that has been found worldwide. Its prevalence is unknown.

Cause

• Stüve-Wiedemann syndrome is usually caused by mutations in the LIFR gene.
• This gene provides instructions for making a protein called leukemia inhibitory factor receptor (LIFR).
• Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks.
• Together, ligands and their receptors trigger signals that affect cell development and function.
• The LIFR protein acts as a receptor for a ligand known as leukemia inhibitory factor (LIF).
• LIFR signaling can control several cellular processes, including growth and division (proliferation), maturation (differentiation), and survival.
• First found to be important in blocking (inhibiting) growth of blood cancer (leukemia) cells, this signaling is also involved in the formation of bone and the development of nerve cells.
• It appears to play an important role in normal development and functioning of the autonomic nervous system.

Gene mutations

• Most LIFR gene mutations that cause Stüve-Wiedemann syndrome prevent production of any LIFR protein.
• Other mutations lead to production of an altered protein that likely cannot function.
• Without functional LIFR, signaling is impaired.
• The lack of LIFR signaling disrupts normal bone formation, leading to osteopenia, bowed legs, and other skeletal problems common in Stüve-Wiedemann syndrome.
• In addition, development of nerve cells, particularly those involved in the autonomic nervous system, is abnormal, leading to the problems with breathing, feeding, and regulating body temperature characteristic of this condition.
• A small number of people with Stüve-Wiedemann syndrome do not have an identified mutation in the LIFR gene.
• Researchers suggest that other genes that have not been identified may be involved in this condition.

Inheritance

Autosomal recessive inheritance, a 25% chance

• This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
• The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Onset

The condition is apparent from birth.

Signs and symptoms

• Its key features include abnormal curvature (bowing) of the long bones in the legs, difficulty feeding and swallowing, and episodes of dangerously high body temperature (hyperthermia).
• In addition to bowed legs, affected infants can have bowed arms, permanently bent fingers and toes (camptodactyly), and joint deformities (contractures) in the elbows and knees that restrict their movement. Other features include abnormalities of the pelvic bones (the ilia) and reduced bone mineral density (osteopenia).
• In infants with Stüve-Wiedemann syndrome, dysfunction of the autonomic nervous system typically leads to difficulty feeding and swallowing, breathing problems, and episodes of hyperthermia.
• Affected infants may also sweat excessively, even when the body temperature is not elevated, or have a reduced ability to feel pain.
• Many babies with this condition do not survive past infancy because of the problems regulating breathing and body temperature; however, some people with Stüve-Wiedemann syndrome live into adolescence or later.
• Problems with breathing and swallowing usually improve in affected children who survive infancy; however, they still have difficulty regulating body temperature.
• In addition, the leg bowing worsens, and children with Stüve-Wiedemann syndrome may develop prominent joints, an abnormal curvature of the spine (scoliosis), and spontaneous bone fractures.
• Some affected individuals have a smooth tongue that lacks the bumps that house taste buds (fungiform papillae).
• Affected children may also lose certain reflexes, particularly the reflex to blink when something touches the eye (corneal reflex) and the knee-jerk reflex (patellar reflex).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal autonomic nervous system physiology
• Abnormality of vision(Abnormality of sight)
• Camptodactyly of finger(Permanent flexion of the finger)
• Feeding difficulties in infancy
• Hyperhidrosis(Excessive sweating)
• [[Hypohidrosis](Decreased ability to sweat)
• Metaphyseal widening(Broad wide portion of long bone)
• Micromelia(Smaller or shorter than typical limbs)
• Paresthesia(Pins and needles feeling)
• Recurrent fever(Episodic fever)
• Short stature(Decreased body height)
• Skeletal dysplasia
• Thickened cortex of long bones

30%-79% of people have these symptoms

• [[Apnea ]]
• Asthma
• Elbow flexion contracture(Contractures of elbows)
• Genu valgum(Knock knees)
• Impaired pain sensation(Decreased pain sensation)
• Intrauterine growth retardation(Prenatal growth deficiency)
• Knee flexion contracture
• Lacrimation abnormality(Abnormality of tear production)
• Oligohydramnios(Low levels of amniotic fluid)
• Osteopenia
• Osteoporosis
• Recurrent fractures(Increased fracture rate)
• Respiratory distress(Breathing difficulties)
• Scoliosis
• Smooth tongue(Smooth surface of tongue)
• Talipes equinovarus(Club feet)
• Trismus(Lockjaw)

5%-29% of people have these symptoms

• Abnormality of the dentition(Abnormal dentition)
• Absent patellar reflexes(Absent knee jerk reflex)
• Decreased corneal reflex
• Ectopic thyroid(Abnormal thryoid location)
• Hypothyroidism(Underactive thyroid)
• Muscular hypotonia(Low or weak muscle tone)
• Sacral dimple(Spinal dimple)

Diagnosis

Biochemical Genetics Tests

• Enzyme assay

Molecular Genetics Tests

• Sequence analysis of the entire coding region
• Deletion/duplication analysis
• Sequence analysis of select exons
• Targeted variant analysis

Treatment

• Treatment is mainly symptomatic and should include efforts to prevent choking, physical therapy and/or surgery to address bone abnormalities, efforts to prevent vision loss, and treatment for osteopenia or osteoporosis.
• Caution should be exercised when using anesthesia due to the predisposition to hyperthermia.

NIH genetic and rare disease info

• NIH info on Stuve-Wiedemann syndrome

Stuve-Wiedemann syndrome is a rare disease.

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