Medical Issues

Edited by Katy Phelan, PhD

The diagnosis of Phelan-McDermid Syndrome is associated with loss 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, 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.

NOTE – This list is meant to introduce you to common features of Phelan-McDermid Syndrome. It is a not a comprehensive list and is not intended to guide your medical care. Please consult your physician for specific health care questions.

Arachnoid cysts:
Arachnoid cysts are 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.

Aspiration:
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.

Autism and autistic-like behavior:
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 Phelan-McDermid syndrome have been as high as 84%.

Chronic diarrhea:
Chronic diarrhea refers to loose, watery stools which persist for 4 weeks or more. Depending on the cause of the 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.

Development delays/delay in gross motor milestones:
With Phelan-McDermid Syndrome, your child may not meet milestone 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.

Gastroesophageal reflux:
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.

Growth:
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 or 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.

Hypotonia:
This is a hallmark feature of the Syndrome and is usually the first presenting feature observed in the newborn. 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.

Lymphedema:
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.

Mild dilation of cerebral ventricles:
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 care of a neurologist who may order a brain imaging, such as an MRI. Other neurological problems may include reduced myelination, frontal lobe hypoplasia, agenesis of the corpus callosum, and seizures.

Recurrent otitis media:
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.

Seizures:
The type and severity of seizures is variable in Phelan-McDermid Syndrome. 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 epileptiologist.

Speech delays/absent speech:
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.

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

Vesicoureteral reflux:
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 Phelan-McDermid Syndrome to determine if VUR or other asymptomatic renal problems are present. Individuals with renal anomalies should be monitored by a urologist.

Vision – ptosis/strabismus (lazy eye):
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 extensive use of peripheral vision and in poor depth perception.

 

PHYSICAL FEATURES;

The following is a list of physical features that individuals with Phelan-McDermid Syndrome may have:

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

Down-slanting palpebral fissures:
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 Down syndrome typically have upslanted palpebral fissures, so the eyes slant up.

Dysplastic ears:  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.

Dysplastic toenails:
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.

Epicanthal folds:
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 is typically seen in individuals with Down syndrome.

High arched palate:  The roof of the mouth is higher than usual.   High arched palate is considered a normal variant in the general population but is seen more frequently in Phelan-McDermid Syndrome.

Macrocephaly:
The head may be large 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.

Microcephaly:  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.

Mild facial dysmorphic features:
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.

Single palmar crease:
A single crease (line) along the middle of the palm of the hand is sometimes seen in Phelan-McDermid Syndrome. 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.

Syndactyly of the toes:
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.

REFERENCES

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.

PMSF | Phelan-McDermid Syndrome Foundation