Potocki-Lupski Syndrome

Neurodevelopmental

Mild-to-moderate infantile hypotonia with oropharyngeal dysphagia is common and contributes to poor feeding and mild-to-moderate gross motor delays [Potocki et al 2007, Soler-Alfonso et al 2011]. Poor feeding or poor weight gain can be an initial presentation. Infants and children have significantly lower weight for age, weight for length, and BMI for age than the reference population [Soler-Alfonso et al 2011].

Although gross motor delay is observed in the vast majority, most will achieve independent walking by age two years. Rarely, independent ambulation can be delayed until age four years.

Cognitive impairment is one of the most common characteristics of PTLS [Potocki et al 2007]. The vast majority of individuals tested have moderate intellectual disability [Treadwell-Deering et al 2010].

Speech delay is universal. Standardized testing has revealed expressive and receptive language impairment which can include articulation difficulties and disordered intonation and prosody [Treadwell-Deering et al 2010]. Some individuals may exhibit verbal apraxia.

While there are no formal studies of articulation and language abilities in teens and adults with PTLS, verbal abilities appear to improve both with age and speech therapy. Little data regarding findings in adults are available; however, adults with a confirmed molecular genetic diagnosis who have been clinically evaluated have cognitive challenges.

Sleep-disordered breathing. Although sleep disturbances are not often clinically recognized and significant airway obstruction is not found on examination, abnormalities frequently evident on sleep studies include sleep-disordered breathing such as mild central and/or obstructive sleep apnea [Potocki et al 2007, Neira-Fresneda & Potocki 2015]. Children with sleep apnea may present with snoring or hyperactivity. In addition, periodic limb movement disorder is commonly observed.

Behavioral difficulties identified by objective measures and by parental reports include attention problems, withdrawal, and high levels of hyperactivity and anxiety. Reported deficits in executive functioning include initiating and shifting activities and working memory.

Autism spectrum disorder (ASD) and/or autistic features (decreased eye contact, motor mannerisms or posturing, sensory hypersensitivity or preoccupation, repetitive behaviors, difficulty with transitions, lack of appropriate functional or symbolic play, and lack of joint attention) are seen in affected individuals [Potocki et al 2007, Treadwell-Deering et al 2010, Neira-Fresneda & Potocki 2015]. Using validated scoring systems (ADI-R and ADOS-G), Treadwell-Deering et al [2010] found that approximately 60% of a small cohort of children with PTLS met criteria for ASD.

Congenital Heart Disease

Cardiovascular anomalies are reported in about 40% of individuals with PTLS [Potocki et al 2007, Jefferies et al 2012]. The anomalies can include atrial septal defect and ventricular septal defect, as well as anomalies within the left ventricular outflow track spectrum including bicuspid aortic valve, dilated aortic root, and hypoplastic left heart [Sanchez-Valle et al 2011, Yusupov et al 2011, Bravo et al 2013].

A smaller percentage of individuals with PTLS have rhythm disturbances detected on ECG [Jefferies et al 2012].

Growth Hormone Deficiency

Five of seven individuals in the original description of PTLS had short stature; one of the five had documented growth hormone deficiency [Potocki et al 2000]. In a second study, one of ten individuals had short stature (but not growth hormone deficiency) [Potocki et al 2007]. Subsequently, additional individuals with PTLS and growth hormone deficiency have been identified, including some with hypoglycemia in infancy and short stature in early childhood [Author, personal observation].

Other

Musculoskeletal features of PTLS that can mimic those seen in connective tissue disorders include severe bilateral clubfeet [Dhanaraj et al 2015], joint hypermobility, kyphoscoliosis, pes planus, and long fingers and toes [Martin et al 2008].

Renal anomalies include hypoplastic, multicystic dysplastic kidneys, and hydronephrosis [Goh et al 2012].

EEG abnormalities observed during sleep include slow occipital dominant rhythm and generalized and/or focal epileptiform abnormalities. Clinical or electroencephalographic seizures have not been reported [Potocki et al 2007, Neira-Fresneda & Potocki 2015].

Other findings include the following [Potocki et al 2007, Neira-Fresneda & Potocki 2015]:

• Hyperopia (common, but not significant enough to require corrective lenses in childhood)
• Mild high-frequency sensorineural hearing loss
• Dental malocclusion and dental crowding

Developmental Delay / Intellectual Disability Management Issues

The following information represents typical management recommendations for individuals with developmental delay/intellectual disability in the United States; standard recommendations may vary from country to country.

Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a nationwide federally funded program available in all states.

Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. A "full individual evaluation" (FIE) will occur before placement to determine needed services and therapies and will be subsequently integrated into an individualized education plan (IEP).

Ages 5-21 years

• In the US, an IEP based on the individual’s level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district generally until age 21.
• Discussion about transition plans including medical and financial guardianship, financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.

Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.

In the US:

• Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
• Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Motor Dysfunction

Gross motor dysfunction

• Physical therapy is recommended to maximize strength and mobility and to reduce the risk for later-onset orthopedic complications (e.g., scoliosis). Aquatic therapy and hippotherapy (therapeutic horseback riding) may also be considered.
• Consider use of durable medical equipment as needed (e.g., orthotics, adaptive strollers).
  Physical medicine and rehabilitation evaluations may be warranted [Neira-Fresneda & Potocki 2015].

Fine motor dysfunction. Occupational therapy is recommended to address difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and handwriting.

Oral motor dysfunction. Feeding therapy, typically from an occupational or speech therapist, is recommended for affected individuals who have difficulty feeding due to poor oral motor control and/or sensory aversions, assuming the individual is safe to eat by mouth.

Communication issues. Consider:

• Speech and language therapy to address receptive and expressive language deficits, articulation abnormalities, and verbal apraxia;
• Evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication) for individuals who have expressive language difficulties.

Social/Behavioral Concerns

Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child’s behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst.

Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications when necessary.