Medical Issues & Clinical Care

Medical Advisories

PMS Medical Advisory Committee (MAC) Guidance on Important Treatment Considerations for PMS Patients. From time to time, the PMS Medical Advisory Committee issues important medical information specific to individuals diagnosed with Phelan-McDermid syndrome. You should share this information with your care team. These documents may help when you are planning a treatment, hospital visit or you find yourself in the emergency room.

Medical Issues

The genetic diagnosis of Phelan-McDermid syndrome (PMS) is associated with loss or variation of material from the distal long arm of chromosome 22. The characteristics described in this section are more common in the population with this syndrome than in the general population, although not all of these features are present in each individual with the syndrome. The most commonly occurring features are neonatal hypotonia, global developmental delay, and absent or delayed speech.

Even if your child is not showing symptoms, below is a list of some medical issues of which you should be aware. You may want to discuss these issues with your child’s primary care physician to determine if your child requires further testing and/or treatment by a specialist. This publication is a good basic overview of PMS.

Please note this list is intended to introduce you to common features of PMS, not guide your medical care. Please consult your physician for specific health care questions.

Fluid-filled sacs that can occur on the surface of the brain. They occur in over 15% of individuals with 22q13 deletion compared to about 1% in the general population. Most arachnoid cysts are present early in life and may remain asymptomatic for many years. Enlargement of the cyst can cause increased pressure on the brain and lead to symptoms such as incessant crying bouts, irritability, severe headaches, cyclic vomiting, or seizures. Brain imagining studies, such as MRI, should be performed if a cyst is suspected.

Due to low muscle tone, individuals may have swallowing difficulties that could result in the aspiration of fluids/solids into the airways. Simple aspiration could lead to aspiration pneumonia and cause lung damage. If your child exhibits coughing while swallowing thin liquids and/or solids or has frequent lower respiratory infections, a gastroenterologist and/or pulmonologist should be consulted to determine what treatments are necessary. In severe cases, a feeding tube (GI tube) may be necessary to reduce the risk of aspiration.

Your child may be diagnosed with autism or show some of the features of autism. These include deficits in social communication, difficulty making eye contact, repetitive behavior, and limited or restricted interests. It is not surprising that a child with delayed or absent speech has difficulty in social communication (See speech delays/absent speech). Estimates of the prevalence of autism in PMS have been as high as 84%.

Chronic diarrhea refers to loose, watery stools that persist for 4 weeks or more. Depending on the cause of diarrhea, it may be controlled with a special diet. An individual with diarrhea should be closely monitored to ensure that they do not become dehydrated. Persistent diarrhea may require treatment by a gastroenterologist.

With PMS, your child may not meet milestones for various physical and mental activities. Your child may require continual individualized therapies such as physical therapy (PT), occupational therapy (OT), and speech therapy (ST), and may benefit from other therapies as well, such as hippo/horse therapy, music therapy, and water therapy.

The contents of the stomach may flow back up into the esophagus because of a problem with the muscles in the lower esophagus. If not treated, this could cause severe vomiting and damage to the esophagus. Individuals should be treated by a gastroenterologist and may require medication or other procedures to control reflux.

The birth weight, length, and head size are usually appropriate for gestational age. In general, growth is normal. In childhood and adolescence, the height is usually normal but may be advanced for age. Weight may not be increased, so your child may be described as “tall and thin”. The adult height is usually within the normal range. Head size is variable and may be normal, large, or small for age.

This is a hallmark feature of the syndrome and is usually the first presenting feature observed in the newborn. The decreased tone of skeletal muscles is characterized by weakness/floppiness. It is often associated with difficulty feeding and swallowing, weak cry, and poor head control. Hypotonia should be evaluated by a neurologist.

The swelling of a body part is caused by the abnormal accumulation of lymph fluid in the limbs. This often occurs in the teenage years. Mild cases can be helped by elevation of the affected limb and use of compression stockings. Severe cases may require evaluation by a vascular surgeon.

The ventricles of the brain may be enlarged due to the accumulation of cerebrospinal fluid or because there is less tissue around the ventricle due to delayed brain growth. Mildly enlarged ventricles without other complications may resolve on their own. Cases in which fluid continues to accumulate may require a shunt to reduce the pressure on the brain. As a precaution, individuals should be under the care of a neurologist who may order brain imaging, such as an MRI. Other neurological problems may include reduced myelination, frontal lobe hypoplasia, agenesis of the corpus callosum, and seizures.

Otitis media is inflammation of the middle ear, commonly called an ear infection. Individuals with recurrent ear infections may require medications or insertion of ear tubes by an Ear, Nose and Throat (ENT) specialist.

The type and severity of seizures are variable in PMS. There are mild seizures in which the person has staring spells or “tunes out” but does not have any physical spasms. Other individuals may experience full seizures with loss of consciousness, jerky movements, and stiffening of the joints. These seizures are usually controlled with medication and the affected individual should be under the care of a neurologist or epileptologist.

One of the most common features of individuals with the syndrome is delayed or absent speech. Individuals will benefit from speech therapy and may be able to communicate using sign language or some type of augmentative communication device depending on their cognitive skills and fine motor capabilities. The receptive language is typically better than the expressive language so a child may understand what is said but cannot respond verbally.

Individuals who are immobile may have problems with a subluxing hip joint where the femur bone does not grow properly into the hip joint. These individuals should be under the care of an orthopedist and may require further treatments.

Normally, urine flows from the kidneys through the ureters to the bladder. VUR is an abnormal flow of urine from the bladder, back up the ureter, and back into the kidneys. It is recommended that a renal ultrasound be performed as soon as possible after an individual has been diagnosed with PMS to determine if VUR or other asymptomatic renal problems are present. Individuals with renal anomalies should be monitored by a urologist.

Drooping of the upper eyelid (ptosis) is seen in individuals with this syndrome. The eyes may look partially shut as if they are ready to fall asleep. Wandering eye is referred to as strabismus and may require treatment by an ophthalmologist. Vision difficulties can result in the extensive use of peripheral vision and in poor depth perception.

Physical Features

In addition to the medical issues cited above, individuals with Phelan-McDermid syndrome (PMS) may have the following physical features:

This means having a long skull with a prominent forehead – the head can be measured to determine if your child is dolichocephalic. You may be able to look at your child’s head shape and recognize that it is longer than usual for his/her age group.

The eye openings (the space between our eyelids) are down-slanted, which means that the outer corner of the eye is lower than the inner corner. In contrast, individuals with PMS may have up slanted palpebral fissures, so the eyes slant up.

The ears may be abnormally developed or poorly formed. The external part of the ear may not be folded as much as usual. In addition to being dysplastic, the ears may be large.

Often the toenails are thin, flaky, and peel off easily in the infant and young child. Many parents say they never have to cut their child’s toenails because they flake off spontaneously. As the child gets older, the toenails may become hard and brittle.

The vertical fold of skin on the inner corner of the eye (on each side of the nose) is excessive and covers the inner corner of the eye. This feature may be seen in individuals with PMS.

The roof of the mouth is higher than usual. A high arched palate is considered a normal variant in the general population but is seen more frequently in PMS.

The head may be largely due to an unidentified cause or due to a known cause, such as enlarged ventricles. Macrocephaly has been reported in about 25% of individuals with the syndrome.

This means that the head is small for age and is more common in individuals with short stature. Microcephaly occurs in fewer than 15% of individuals with the syndrome.

This refers to minor facial anomalies that occur fairly frequently and do not pose a significant health risk. The features include ptosis, epicanthal folds, and puffiness around the eyes, puffy cheeks, long thick eyelashes, and down-slanting palpebral fissures. The presence of two or more minor anomalies may prompt a search for major defects and may aid in the diagnosis of a particular syndrome.

A single crease (line) along the middle of the palm of the hand is sometimes seen in PMS. Usually, there are three major creases on the palm: a crease that goes from the pinkie side of the palm and curves up toward the index finger, another crease that starts on the pinkie side of the hand and goes between the index finger and the thumb and the third crease that goes from above the thumb toward the wrist. In individuals with a single palmar crease, there is a straight line across the palm. A single palmar crease is fairly common in the general population occurring in about 1 in 30 individuals.

Webbing or an extra fold of skin that usually occurs between the second and third toes. This is a fairly common variant in the general population and may be inherited from one parent, unrelated to the syndrome.

Aldinger KA, Kogan J, Kimonis V, et al. Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet A. 2013;161A(1):131–136. doi:10.1002/ajmg.a.35700.

Dhar SU, del Gaudio D, German JR, et al. 22q13.3 deletion syndrome: clinical and molecular analysis using array CGH. Am J Med Genet A. 2010;152A(3):573–581. doi:10.1002/ajmg.a.33253.

Kolevzon A, Angarita B, Bush L, et al. Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring. J Neurodev Disord. 2014;6(1):39. doi:10.1186/1866-1955-6-39.

Phelan K, McDermid HE. The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome). Mol Syndromol. 2012;2(3-5):186–201.

Phelan MC, Stapleton GA, Rogers RC. 22q13 deletion syndrome: Phelan-McDermid syndrome. In: Cassidy SB, Allanson JE, eds. The management of genetic syndromes. Hoboken, NJ, USA: Wiley-Liss, Inc. 2010: 285-97.

Rollins JD, Sarasua SM, Phelan K, et al. Growth in Phelan-McDermid syndrome. Am J Med Genet A. 2011;155A(9):2324–2326. doi:10.1002/ajmg.a.34158.

Sarasua SM, Boccuto L, Sharp JL, et al. Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. Hum Genet. 2014;133(7):847–859. doi:10.1007/s00439-014-1423-7.

Soorya L, Kolevzon A, Zweifach J, et al. Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. Mol Autism. 2013;4(1):18. doi:10.1186/2040-2392-4-18.



2023 Clinical Consensus Guidelines

European Clinical Care Guidelines

A team of European experts in Phelan-McDermid syndrome representing 15 countries and more than 70 clinicians, scientists, & patient advocacy representatives have written an updated series of clinical guidelines for PMS. The full guidelines set covers sensory functioning, chewing, swallowing, GI, epilepsy, sleep, communication, organization of care, lymphedema, mental heath, and counseling.  

A short version of the guidelines : CLINICAL SYNOPSIS

The entire set of European Clinical Care Guidelines is found in the document library on this website. Publications are added as they are released. You may use the library to search on topics or titles or the term “european” to access the publications.

You may also access individual files from this menu:

International/U.S. Clinical Care Guidelines

The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014 (see graphic and publication link below); recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and largescale genotype–phenotype investigations.

The objective of these updated clinical management guidelines was to:

  1. reflect the latest in knowledge in PMS
  2. provide guidance for clinicians, researchers, and the general community.

A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders.

Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts.

You may access the publication by clicking the link below:

2014 Clinical Care Guidelines

Below is an infographic, based on a publication titled “Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring” Kolevzon et al. Journal of Neurodevelopmental Disorders 2014, Sinai Seaver Autism Center.  This infographic is a tool that can be used by patients to begin discussions with their own clinician.  Please note that all cases of PMS are different and your doctor/clinician is the best resource to help you make clinical care decisions for your loved one.  Also note that material on the website is subject to change, so always refer back to the website for the latest updates.

To Print or Download the infographic, click on the icons that are on the top, right side of the screen (Print = printer icon; Download = page with down arrow).  To Open the infographic, click on the >> on the top, right side of the screen to display the menu.