Table 1.
Overview of the reported phenotypic features of individuals #1–#8 in childhood, as well as the respective phenotypes in adulthood including food intake, behavior, autonomy, and medical conditions
| Individual # | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
|---|---|---|---|---|---|---|---|---|
| Age (years) | 25 | 30 | 26 | 20 | 18 | 18 | 36 | 55 |
| Gender | F | M | F | M | M | F | F | M |
| MAGEL2 variant (NM_019066.4) |
c.2874G > A p.Trp958* |
c.1800delT p.Pro601Glnfs*101 |
c.1819C > T p.Gln607* |
c.2958delG p.Ser987Alafs*5 |
c.1996dupC p.Gln666Profs*47 |
c.1790delC p.Pro597Hisfs*105 |
c.2821dupC p.Arg941Profs*10 |
c.2170_2232dup p.Ser724_Ala744dup |
| Inheritance | De novo | De novo | Paternal | De novo | Paternal | Unknown | Unknown | Unknown |
| Height (cm) | 144.8 | 170 | n.s | 175.9 | 148 | 174 | 147 | 160 |
| BMI (kg/m2) | 31.4 | 41.2 | n.s | 30.6 | 22 | 31.7 | 32 | 51.6 |
| Head circumference (cm) | n.s | 56 | n.s | n.s | n.s | 54 | 55 | 57 |
| IQ | Mild intellectual disability | Mild intellectual disability | n.s./n.a | Learning disability (WAIS-IV full scale: 84) | n.s | Learning disability (74–85) | n.s | Mild intellectual disability (WAIS-IV: 67) |
| Phenotype in childhood | ||||||||
| Birth weight (kg) | 2.35 | 3.33 | 2.61 | n.s | 2.89 | 3.42 | 3.28 | n.s |
| Birth length (cm) | n.s | 50 | n.s | n.s | 48.3 | 54 | 46 | n.s |
| Head circumference (cm) | n.s | 36.5 | 32.7 | n.s | n.s | 36 | n.s | n.s |
| Gestational week | 35 | 40 | 35 | n.s | n.s | 40 | 38 | n.s |
| Decreased fetal movement | n.s | Yes | n.s | n.s | n.s | Yes | n.s | n.s |
| Congenital contractures of interphalangeal joints | Yes | Yes | Yes | Yes | Yes | No | Yes | n.s |
| Neonatal hypotonia, poor suck | Yes | Yes | Yes | Yes | Yes | Yes | No | n.s |
| Feeding problems in infancy | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes |
| Nasogastric tube feeding | n.s | Yes | Yes | n.s | Yes | Yes, for 1 mo | No | n.s |
| Motor development | Delayed | Delayed | Severely delayed, never walked | Delayed | Delayed | Delayed | Delayed | Delayed |
| Language development | Delayed | Delayed | None | Delayed | Delayed | Normal | n.s | n.s |
| Speech, articulation defects | n.s | Fluent, mild (sometimes slurred speech) | n.a | n.s | First words at 11 years of age | Fluent | Strong verbal qualities | Fluent, mild |
| Excessive weight gain before the age of 6 years | n.s | Yes | No | No | No | Yes | n.s | Possibly Yes |
| Phenotype in adulthood | ||||||||
| Food intake, metabolism and sleep (− = never; + = 1–3 times/month; ++ = 1–3 times/week; +++ = 4–7 times/week) | ||||||||
| Overeating | +++ | +++ | n.a. (PEG tube) | +++ | − | + | + | +++ |
| Food-seeking behavior | ++ | +++ | n.a | +++ | − | + | + | ++ |
| Sleep apnea | + | +++ | − | +++ | +++ | − | n.s | +++ |
| Need for assisted ventilation (CPAP, BIPAP) | − | +++ | − | +++ | +++ | − | − | +++ |
| Abnormal sleep cyclea | ++ | ++ | +++ | + | +++ | + | ++ | +++ |
| Excessive sleeping/daytime fatigue | +++ | ++ | +++ | +++ | +++ | −/+ | − | ++ |
| Constipation | +++ | ++ | − | ++ | +++ | + | − | +++ |
| Behavior and psyche (− = not present and/or not an issue; + = infrequent and/or not a big issue; ++ = frequent and/or sometimes a big issue;+++ = almost always present and/or a major concern) | ||||||||
| Hyperactivity | ++ | − | − | + | − | − | − | ++ |
| Underactivity | ++ | +++ | − | ++ | n.s | +++ | ++ | +++ |
| Stubbornness | +++ | ++ | − | ++ | ++ | + | ++ | +++ |
| Temper tantrums | + | + | − | ++ | − | − | − | ++ |
| Aggression | + | − | − | − | − | − | − | ++ |
| Lying, deceitfulness | +++ | − | n.a | ++ | − | − | + | + |
| Stealing | +++ | − | n.a | ++ | − | − | + | ++ |
| Manic, excited mood | +++ | ++ | − | − | − | − | − | ++ |
| Depressive mood | + | ++ | − | + | − | − | − | +++ |
| Anxiety | ++ | + | − | ++ | + | +++ | + | +++ |
| Social withdrawal | +++ | + | n.a | + | − | + | + | +++ |
| Restricted interests | +++ | n.s | n.a | ++ | ++ | ++ | + | ++ |
| Self-stimulatory behavior | + | +++ | − | − | ++ | − | − | + |
| Skin picking | +++ | − | − | + | − | − | + | +++ |
| Autonomy and activities | ||||||||
| Communication | Verbal | Verbal | None | Verbal | Mostly nonverbal, ≤ 50 Signs/gestures | Verbal | Verbal | Verbal |
| Reading skills | Basic | Not present | Not present | Basic | Basic | Good | Good | Good |
| Awareness of danger | Severely reduced | Reduced | Severely reduced | Reduced | Severely reduced | Severely reduced | Reduced | Normal |
| Can take care for basic needsb | Yes, but help is required in certain areas | Sometimes, but help is required regularly | No | Yes, but help is required in certain areas | No | With help | Yes, but help is sometimes required | Yes |
| Performs basic (housekeeping) choresc | No/mostly not | Sometimes | No | Regularly | No | No/mostly not | Sometimes | Sometimes |
| Performs more complex (everyday) activitiesd | No/mostly not | No/mostly not | No | Sometimes | No | No/mostly not | Regularly | Sometimes |
| Sports/physical activities | No/mostly not | Regularly | No | Sometimes | Sometimes | Occasionally | No | No |
| Works (e.g. in a sheltered environment) | No/mostly not | Regularly | No | Regularly | No | Regularly | Regularly | No |
| Medical conditions, medication | ||||||||
| Hypothyroidism | No | Yes | No | Yes | No | No | No | Yes |
| Hypogonadisme | n.s | Yes | Yes | No | No | No | No | Yes |
| Type 2 diabetes | No | No | No | No | No | No | No | No |
| Hypertension | No | No | No | No | No | No | No | Yes |
| Scoliosis | Yes | Yes | Yes | No | Yes | No | Yes | No |
| Autism spectrum disorder | Yes | No | n.a | Yes | Yes | Yes (Rocking body movements) | No | No |
| Attention deficit disorder | Yes | No (?) | n.a | n.s | n.s | n.s | No | n.s |
| Obsessive compulsive disorder | Yes | No (?) | n.a | Yes | n.s | n.s | No | No |
| Growth hormone therapy | Yes | No | No | No | Yes | No | No | No |
| Use of melatonin | No | No | No | Yes | No | No | No | No |
n.s. not specified, n.a. not applicable
aA sleeping routine that is different from the normal sleep cycle (e.g. sleeping from 2 pm to 1 am). A “reverse” sleep cycle would be the most extreme form
bE.g. getting dressed, using the toilet, basic body hygiene
cE.g. cleaning his or her room, preparing food
dE.g. buying groceries, or using public transport
eDefined as repeatedly low levels of sex hormones