The congenital anomalies associated with MSS are present before birth, however the underlying defects are not typically detected during standard prenatal care. Many mothers experience excess amniotic fluid (polyhydramnios) during pregnancy, potentially due to fetal airway and swallowing problems. Other times routine fetal ultrasound can detect some brain or skeletal abnormalities. Standard prenatal genetic screening blood tests do not test for the gene that causes MSS. Pregnancies generally progress to full-term, however, some babies are born prematurely. Though it may not be easily detected in the prenatal period, Marshall-Smith Syndrome is present in the child at birth and does not develop later in life.
Infants usually present with upper airway obstruction and respiratory distress due to a displaced tongue, floppy throat tissue, and/or narrow nasal passages (in medical terms: glossoptosis, laryngomalacia, and choanal stenosis). There is a wide range of severity with regard to airway obstruction. Some newborns with MSS can breathe on their own at birth; others can not and require resuscitation and intubation immediately after delivery. Babies who can breathe on their own may eventually experience trouble with feeding or noisy breathing (stridor). Low muscle tone (hypotonia) is common, and upon examination some of the syndromic features in the face, hands, and feet may also be noticed.
Childhood, Adolescence and Adulthood
In early childhood, the most medically serious complications in MSS are the associated respiratory problems. Structures in the airway may not function properly because they are less muscular than usual and collapse easily. The nasal passages may be narrow (stenosis), closed off completely (atresia), or a combination of both. Many infants with MSS require a nasopharyngeal airway tube or tracheostomy. Others may have a surgery to pull the lower jaw forward (mandibular distraction). The inner ear canal and eustachian tubes can also be narrow and floppy, causing frequent ear infections. Even in children able to breathe adequately, even mild narrowing can disrupt proper movement of air through the nose and mouth. Because of this, upper respiratory infections are common and can spread to the lungs (pneumonia) and become life-threatening.
The congenital upper airway obstructions typically cause feeding problems in infants and young children with MSS. Additionally, babies may have a weak suck and an uncoordinated swallow. Often, a feeding tube is necessary for calorie supplementation, and in severe cases, nutrition is delivered exclusively via tube. Temporary feeding tubes can include nasogastric (NG) or orogastric (OG) tubes. It is common for a child with MSS to eventually receive a g-tube (gastrostomy), as many children cannot take in enough food by mouth to maintain good health. If the primary issues with breathing and feeding are managed, most children with MSS grow slowly along their own curve into adolescence. Once growth plates close, which is at a younger age than usual, individuals with MSS do not tend to grow much more in height or weight.
Advanced bone age is present in all people with MSS, who often have generalized accelerated bone maturation within their entire skeleton. The bones often lose density quickly in early childhood, leading to osteopenia and, eventually, osteoporosis. This can put the child with MSS at a high risk of non-traumatic fractures. Other common musculoskeletal issues include hypermobility of joints, hip dysplasia, and (notably) scoliosis. It is important for the spine to be monitored closely by an orthopedic specialist, because with MSS, scoliosis tends to have a rapid onset and can quickly become severe. Many people with MSS require surgical intervention to correct severe spinal curvature, and often at a much younger age than the general population.
There are many other conditions that seem to occur commonly in the population of children and adults with Marshall-Smith Syndrome. With so few cases, it is hard to know definitively whether these other medical issues are directly related to MSS or the genetic defects caused by MSS. It is understood that for some patients MSS affects almost every body system to a degree, however more research is needed. Epilepsy is an issue with several individuals, while some others are considered “at risk” for seizures due to abnormal brain waves. Vision impairments are frequently seen and include (but are not limited to) nearsightedness, glaucoma, and issues related to bulging eyes being overexposed. Many with MSS also have some level of hearing loss. There is partial to complete lack of speech, though the exact reason for this is not known. Caregivers report that children and adults with MSS seem to understand questions, conversation, stories, etc., even if they can’t always respond or interact verbally.
Development is globally delayed, but everyone with MSS has the ability to learn basic knowledge and skills along their own path. Early intervention therapies (physical, occupational, speech language, vision, etc.) can help foster development and set the young child up for success. Some with MSS exhibit behaviors consistent with autism spectrum disorder. Adolescents usually enter puberty before their typical peers. Adults with Marshall-Smith Syndrome are not able to live independently and typically require round-the-clock care. This does not, however, stop them from participating in society and living full and happy lives.