Angelman syndrome (AS) | UBE3A 1 | Recurrence risk is mechanism dependent. 2 | Severe DD or ID, severe speech impairment, gait ataxia &/or tremulousness of the limbs, & unique behavior w/happy demeanor, frequent laughing, smiling, & excitability. Microcephaly & seizures are common. Hypotonia may be the only manifestation of AS in infancy. Affected persons lack characteristic sucking issues, hypogonadism, & facial appearance of those w/PWS. |
Congenital myasthenic syndromes (CMS) | >30 genes incl: CHAT CHRNE COL13A1 COLQ DOK7 RAPSN | AR AD 3 | Typically presents w/fatigable weakness involving ocular, bulbar, & limb muscles w/onset typically age <2 yrs. In the classic presentation, a CMS is limited to weakness of skeletal muscles. |
Congenital myotonic dystrophy type 1
|
DMPK
| AD | Hypotonia & severe generalized weakness at birth, often w/respiratory insufficiency & early death; ID is common. |
Fragile X syndrome (See FMR1 Disorders.) |
FMR1
| XL | Moderate ID in affected males & mild ID in affected females. Males may have a characteristic appearance, connective tissue findings, & large testes (post pubertal). Behavioral abnormalities are common. Hypotonia may be the only manifestation in infancy. Affected persons lack characteristic sucking issues, hypogonadism, & facial appearance of those w/PWS. |
GARS1 infantile-onset SMA (See GARS1-Assoc Axonal Neuropathy.) |
GARS1
| AD | Initial manifestations are typically respiratory distress, poor feeding, & muscle weakness (distal > proximal). |
Infantile-onset Pompe disease |
GAA
| AR | Onset is typically at median age of 4 mos w/hypotonia, generalized muscle weakness, feeding difficulties, poor weight gain, respiratory distress, & hypertrophic cardiomyopathy. (Note: In PWS, hypotonia is noted at birth, not several months later.) |
Schaaf-Yang syndrome
|
MAGEL2
| AD w/imprinting 4 | Hypotonia & feeding difficulties in infancy are similar to PWS, but joint contractures incl arthrogryposis are features not typical of PWS. ASD is frequent as well as ID, which can be profound. Some persons develop obesity & hyperphagia in late childhood/adolescence that ↑ w/age. |
Spinal muscular atrophy
|
SMN1
| AR | Poor respiratory effort may be present, a feature rarely seen in PWS. |
WAC-related ID
|
WAC
| AD | Variable degrees of DD &/or ID. Behavioral abnormalities are observed in the majority of older children & adults. Most affected infants have significant but nonspecific features at birth (e.g., neonatal hypotonia, feeding issues). |
X-linked infantile SMA
|
UBA1
| XL | Congenital hypotonia, areflexia, & evidence of degeneration & loss of anterior horn cells (i.e., lower motor neurons) in spinal cord & brain stem. Often congenital contractures &/or fractures are present. |
Zellweger spectrum disorder (ZSD) | ZSD-PEX genes | AR 5 | Affected newborns are hypotonic w/poor feeding. They have distinctive facies, congenital malformations, & liver disease that can be severe. (Note: The brain MRI findings are very striking & distinctive in ZSD, while the brain MRIs of persons w/PWS are typically relatively normal.) |