Table 1 Genotypes and phenotypic features of individuals 1–6.

From: Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

Individual 1 2 3 4 5 6
Age/sex/BMI 13 years/M/ unknown 16 years/F/29.9 7 years/M/unknown 7 years/M/32.5 7 years/M/17.3 3 years/M/17.9
Variant (NM_001164760) c.586G>A, p.Glu196Lys c.500_501inv, p.Gln167Leu c.1003C>T, p.Arg335Trp c.1003C>T, p.Arg335Trp c.1003C>T, p.Arg335Trp c.1003C>T, p.Arg335Trp
De novo? Yes Unknown Yes Yes Yes Yes
Global developmental delay Yes Yes Yes Yes Yes Yes
Diagnosed ASD Yes Yes Yes Yes Yes Yes
ADHD Yes Unknown Yes Suspected by parents, no formal diagnosis Yes Yes
Dyspraxia /apraxia Yes Yes Yes Yes Yes Yes
Congenital hypotonia Unknown Unknown Unknown Yes Yes Yes
Speech Speech delay Speech delay Speech delay Speech regression, nonverbal Speech delay, 1–3 word sentences Speech delay and regression, single words
Other behavioral anomalies Aggression Immature for age No Aggression, hand flapping Arm flapping, aggression when frustrated Odd/repetitive behaviors, arm flapping, happy demeanor, sensory-seeking
Pain tolerance Normal Unknown Unknown High Very high High
Other neurologic anomalies Tremor, Hemidystonia Seizures No No No Eye twitching
Physical anomalies Upslanting palpebral fissures Upslanting palpebral fissures, other dysmorphic featuresa No Obesity, astigmatism, esotropia, upslanting palpebral fissures, other dysmorphic featuresb Microcephaly, upslanting palpebral fissures Torticollis, plagiocephaly, submucosal cleft palate dysmorphic featuresc
Skill regression No Unknown No No No Potential skill regression and plateauing of progress
Other features Unknown Asthma, fatigue Sleep problems, nocturnal enuresis Obstructive sleep apnea, recurrent otitis media Sleep disturbance, severe eczemad Restlessness, obstructive sleep apnea
  1. ADHD attention deficit hyperactivity disorder, ASD autism spectrum disorder, BMI body mass index.
  2. aRound face, broad nasal tip, thin upper lip, and short palpebral fissures.
  3. bHypotelorism, bitemporal narrowing, epicanthal folds, flat nasal bridge, downturned mouth, tapered fingers, doughy hands, and brachydactyly (Fig. 1a).
  4. cEpicanthal folds, slightly posteriorly rotated ears (Fig. 1a).
  5. dIndividual 5 is also homozygous for a pathogenic variant in FLG (c.2282_2285delCAGT; p.Ser761Cysfs*36), which explains his severe eczema and dry skin.