Phelan- McDermid syndrome

Phelan–McDermid syndrome (synonym: 22q13 deletion syndrome, monosomy 22q13) is a rare genetic disorder caused by damage to a segment on the long arm of chromosome 22 (deletion/monosomy). The severity of symptoms varies widely, but the most characteristic features include low muscle tone (hypotonia), normal or accelerated growth, absent or severely delayed speech, moderate to severe intellectual disability, and distinctive facial features. In some cases, there is also delayed psychomotor development. Current research shows that the genetic deletion leads to the formation of a defective protein responsible for most neurological symptoms (including psychomotor delay and absence of speech).

Diagnosis:
The deletion typically arises spontaneously (de novo) due to a break in the long arm of chromosome 22 of unknown cause (sporadic occurrence). The parents of the affected child are usually healthy with a normal genetic makeup; the mutation occurs randomly in one of the parental germ cells (egg or sperm).

 The incidence of Phelan–McDermid syndrome is difficult to estimate due to its rarity, but it is approximately 2.5–10 per 1 million live births. Diagnosis is performed using molecular biology methods. Prenatal ultrasound usually shows a healthy fetus. Some renal abnormalities may be detectable during pregnancy, but these do not necessarily indicate the presence of this syndrome. During pregnancy, amniocentesis and chorionic villus sampling can be performed.

Treatment:
Therapy is individualized for each person with Phelan–McDermid syndrome and requires coordination of a wide range of specialists, including a pediatrician, nephrologist, neurologist, gastroenterologist, immunologist, orthopedist, social worker, special education specialist, and speech therapist. Cardiac abnormalities are not typical for this syndrome, but echocardiography by a cardiologist is still recommended. Surgical interventions are individualized depending on severity. Other treatment is supportive and symptomatic.

• Phelan–McDermid syndrome is characterized by moderate to severe intellectual disability. Speech development is typically delayed, and some children are non-verbal. Receptive language skills (understanding) are generally better developed than expressive language abilities. Delayed psychomotor development is also common.
• Prenatal growth is usually normal; after birth, growth is normal or above average. One of the earliest signs is neonatal hypotonia (reduced muscle tone), which correlates with feeding difficulties, poor feeding, weak crying, and inability to hold the head up. As part of delayed psychomotor development, infants begin to roll over, crawl, and walk later than usual, which is associated with hypotonia.
• Facial features of Phelan–McDermid syndrome include a long head shape (dolichocephaly), large prominent ears, thick eyebrows, deep-set eyes, long eyelashes, ptosis (drooping eyelids), full or puffy eyelids, a flat midface, full cheeks, a broad nasal bridge, a larger nose, and a pointed chin. Other physical features may include relatively large hands and underdeveloped thumbnails. Behavior is often described as “autistic-like”, with hypersensitivity to touch, social anxiety or avoidance of social situations, reduced eye contact, and presence of stereotyped behaviors. Additional characteristics may include increased pain tolerance and a tendency to chew on various objects.
• About 25% of individuals with Phelan–McDermid syndrome have kidney abnormalities, such as polycystic kidneys, renal dysplasia (one non-functional kidney), kidney stones, and vesicoureteral reflux (urine flows back toward the kidneys, which may then enlarge). Therefore, renal ultrasound is recommended for all children with Phelan–McDermid syndrome.
• More than 15% of patients have arachnoid cysts (fluid-filled cavities in parts of the brain), compared to about 1% in the general population. Small cysts are usually asymptomatic, while larger cysts may cause increased intracranial pressure, which can present with irritability, restlessness, episodes of crying, severe headaches, recurrent vomiting, and seizures. This condition and the presence of cysts can be diagnosed using CT scan of the head or brain MRI.
• Some individuals report the development of swelling of the limbs, especially the lower extremities, and cellulite, which may appear during adolescence or early adulthood.