Marshall et al. first described this rare congenital disorder in 1971 as a sporadic entity of unknown etiology [4, 5]. Patients classically have a normal karyotype and are born of nonconsanguineous parents [4]. Most significantly, they display skeletal maturation that is advanced for age, along with osteopenia and sclerosis, leading some to describe this kind of ossification as "disharmonic" [6–8]. Skeletal abnormalities like broadened phalanges with abnormal epiphyses, thinned or bowing long bones, and dysmorphic vertebrae leading to scoliosis, kyphosis, or cervical, thoracic, or lumbar instability are commonly present [[3–5, 7–9], Figure 3, Figure 4, Figure 5, Figure 6]. Specific facial anomalies may include hypertrichosis, prominent eyes and forehead (frontal bossing), megalocornea, blue sclerae, a flat nasal bridge, micrognathia, and anteverted nostrils [5, 10]. Neurologic derangements may consist of an absent corpus callosum, macrogyria, ventricular dilatation or hydrocephalus, periventricular leukomalacia, resulting in motor and mental retardation [5, 10]. They might also display optic nerve hypoplasia [11]. It should be noted that not all patients afflicted with MSS display the same anatomic findings.
Most infants affected with MSS succumb to death early in life. This is usually due to pulmonary complications, such as aspiration and chronic lung obstruction leading to pulmonary infections, pulmonary hypertension, and right heart failure [2, 4, 5, 10–13].
The concept of applying viscosupplementation (VS), using modified hyaluronic acid to form hyaluronans (HA) and their cross-linked derivatives, to the treatment of osteoarthritis arose in the mid 1970's, though these compounds had also been investigated for use in various ophthalmologic procedures [14–17]. As joints affected by osteoarthritis are depleted of their natural synovial fluid, which contains the glycosaminoglycan hyaluronic acid, it was postulated that injecting exogenous HA would increase the viscosity and elasticity to the joint, thereby improving joint function and relieving symptoms [18, 19]. While research on, and FDA-approval of, VS is primarily for use in the treatment of knee osteoarthritis, it has also been used successfully in small trials for the treatment of arthritis of the temporomandibular, sacroiliac, hip, shoulder, foot, and ankle joints [17, 20–23]. In 1997, Hyalgan® (sodium hyaluronate), a high molecular-weight HA obtained from rooster's combs, was approved by the FDA [24, 25]. Like other HA, it is only approved for osteoarthritis of the knee, and should be used with caution in patients with sensitivities to avian proteins, feathers, and egg products. It also carries a similar side-effect profile, including local inflammation, injection site pain and itching, anaphylaxis/anaphylactoid reactions, local ecchymosis, nausea/vomiting, diarrhea, anorexia, and headache [26]. While Hyalgan© has a relatively short half-life of about twenty-four hours, the effect of the injections lasts for weeks, which suggests that it augments natural synovium production, mitigates nociception and inflammation, as well as increases the rheological properties (viscosity, elasticity, pseudoplasticity) of synovial fluid [27–29].
Our patient's survival to adulthood is somewhat anomalous, compared to the life expectancy of others afflicted with MSS. Therefore, we can only assume that if other carriers of the disease survived the historically perilous respiratory maladies of childhood, they too would suffer from the chronic pain of disharmonic skeletal development and ensuing arthralgias, as we observed in our patient, and as it has been noted in other carriers [13]. L.W. underwent a series of three intra-articular bilateral hip injections one week apart, and gradual improvement in symptoms over this period was noted. At the time of the first visit, the patient arrived in her wheelchair, and passive movement of her hips caused her great distress. Two months after the last injection, we reevaluated the patient in our clinic. She arrived for her appointment walking, semi-independently, with her parents on either side of her. They felt that the injections successfully decreased the frequency and intensity of her painful episodes, noting a marked improvement in her daily functioning.