Autosomal Dominant Intellectual Disability-17; Intellectual Disability-Craniofacial Dysmorphism Cryptorchidism Syndrome; PACS1 Neurodevelopmental Disorder; PACS1-NDD; PACS1 Related Syndrome; Schuurs-Hoeijmakers Syndrome; SHMS

PACS1 syndrome is a rare neuro-genetic disorder caused by mutations in the PACS1 gene. It is characterized by mild-to-severe neurodevelopmental delays. Language skills are affected more severely than motor skills. Hypotonia (decreased muscle tone) is reported in about a third of individuals and is noted to improve over time.

Approximately 60 percent of individuals are ambulatory. Feeding difficulty is common, with 25 percent requiring gastrostomy tube to maintain appropriate caloric intake. Other common features include constipation, seizures, behavioral issues, congenital heart anomalies, short stature, and microcephaly. Many affected individuals have additional neurological, behavioral, and health problems. PACS1 syndrome mostly occurs in children, and rarely occurs in adults.

The prevalence of PACS1 syndrome is unknown; more than 30 affected individuals have been described in the scientific literature.

Diagnostic testing: The diagnosis of PACS1 syndrome is based on:

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  Symptoms;

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  Clinical examination; and

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  Genetic testing for mutation of the PACS1 gene.

Physical findings: The physical signs and symptoms of PACS1 syndrome include:

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  Distinctive facial appearance;

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  Thick and highly arched eyebrows;

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  Long eyelashes;

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  Widely set eyes (hypertelorism);

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  Outside corners of the eyes that point downward (down slanting palpebral fissures);

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  Droopy eyelids (ptosis);

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  Rounded nasal tip;

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  Wide mouth with corners that point downward;

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  Thin upper lip;

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  Smooth area between the nose and upper lip (philtrum);

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  Widely spaced teeth;

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  Ears that are low-set with fewer folds and grooves than normal;

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  Malformations of the heart, brain, eyes, or other organs; and

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  Males may have undescended testes (cryptorchidism).

ICD-9: 755.5; 758.9

ICD-10: Q87.0

Symptoms may begin as a newborn, infant, in a single age range, or during several age ranges. In PACS1 syndrome, intellectual disability typically ranges from mild to moderate. Individuals with this condition also have problems with producing speech (expressive language). Speech development ranges from limited language to few words or no speech.

Children with PACS1 syndrome often have problems learning to eat solid food and prefer soft foods. When given solid foods, affected children often swallow without chewing. These food issues tend to persist throughout life. Some affected individuals experience a backflow of stomach acids into the esophagus (gastroesophageal reflux).

Additional neurological problems can occur in PACS1 syndrome. Some affected individuals have features of autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), self-injury, or frustration leading to tantrums can also occur. Most individuals with PACS1 syndrome have seizures that vary in type and age of onset. Some individuals with PACS1 syndrome have weak muscle tone (hypotonia). Individuals with this condition are often delayed in walking, with some developing an unsteady walking style (gait). Rarely, affected individuals have frequent falls and gradually lose their ability to walk in late childhood, requiring wheelchair assistance.

There is no curative treatment for this syndrome. Treatment is symptom specific and supportive. Treatment by a multidisciplinary team is needed to address feeding issues, constipation, seizures, behavioral issues, cardiac anomalies, vision issues, and renal anomalies. Medication to prevent seizures and placement of a feeding tube to help with weight gain may be warranted.

Suggested MER for Evaluation:

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  Clinical history and physical examination that describes the diagnostic features of the impairment; and

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  Genetic sequencing tests confirming mutation of the PACS1 gene.

Suggested Listings for Evaluation:

REMARKS

Evaluate the most severe forms of PACS1 Syndrome under 110.08 A or B.

For less severe, late onset forms, evaluate under the affected body systems.