Table 2.
Activity-dependent neuroprotective protein (ADNP) phenotype data questionnaire (Facebook™, A–D); (E) selected children with ADNP p.Tyr719* mutation (featured also in Figure 1C); Facebook data.
| A | |||
| cDNA/nucleotide | c.2157C>G | ||
| Protein—pchange | p.Y719 | ||
| Zygosity | Heterozygous | ||
| Inherited/de novo | De novo | ||
| Location | USA | ||
| Sex | Female | ||
| Birthday | 01/10/2005 | ||
| Pregnancy or birth complications? | Meconium stained from AD imperforate anus | ||
| Birth weight | 7.8 lbs | ||
| Developmental | – | ||
| Gross motor delay | Yes | ||
| Intellectual disability | Originally diagnosed as severe—at the age of 10 diagnosed as moderate | ||
| Speech delay (has under 25 understandable words) | Apraxia/speech delay | ||
| Have you done prompt, rest, or other “oral motor planning” types of therapy or “general speech therapy” | Yes | ||
| Can your child write? | Age 10: now writes her name with hand over hand assistance and used handwriting with no tears program. Primarily a “motor planning issue” needs repetition and tracing. She is also able at age 10 to recognize certain site words on Flashcards especially written in red which helps her cortical vision impairment (CVI) | ||
| Can your child feed him/herself with utensils? | Yes, with spoon | ||
| Neurological/brain | – | ||
| Has your child had a magnetic resonance imaging (MRI) brain scan? | At 2 years (no findings) and at 9 years (Figure 1A) | ||
| Does your child have a brain abnormality? | Slight diminishing of white matter in the cerebellum (9 years of age) | ||
| Regression of skill? | Slight when not working consistently | ||
| Facial palsy/bells palsy? | Left side facial palsy | ||
| B | |||
| Behavior | – | ||
| Autism spectrum disorder (ASD) diagnosis? | At 2 years of age | ||
| Did you have a hard time getting an ASD diagnosis? | No—however, socializes with adults important: at 3.5 years of age when she achieved stages of independent and functional walking and attained mobility, she started opening up and was able to access her environment and peers. She grows and flourishes (and still does at age 10) having “inclusion” and access to her normally developing peers. AD “wants” to play but her lack of speech makes connecting difficult on many levels. | ||
| Rocks back and forth or shakes head when excited | No (claps her hands and makes noise or word approximation) | ||
| Like to rub or twirl fingers and hands, sometimes close to face for stimulation? | Yes | ||
| Does/did your child love to be around most adults, not just family (loving, eye contact, happy with adults, especially as an infant/young toddler)? | Yes | ||
| Does your child interact or directly socialize with other children? | No (starting to develop as she attained mobility) | ||
| Does your child like “indirect” interaction with children? (prefers to play alone by other children, but not with them) | Yes | ||
| Does/did your child have an extremely loving, friendly, affectionate/cuddles demeanor as a baby/young toddler? | Yes | ||
| Does your child line up or stack items compulsively? | No | ||
| Does your child have an extreme love for music? | Yes!! | ||
| Does your child have an extreme love for water (in water or splashing/playing with water)? | Yes | ||
| Sensory processing disorder? | Yes | ||
| Enjoys/loves “swinging” = vestibular stimulation | Yes | ||
| ADHD diagnosis? | No | ||
| OCD diagnosis? | No | ||
| Anxiety disorder? | No | ||
| BAD Behavior, does/did your child have increased BB in early childhood? | Yes | ||
| What age did “bad” behaviors begin (symptoms) | 2 (head banging, hair pulling, copying with waiting, violent behavior—improvements as she matures) | ||
| C | |||
| Vision | – | ||
| Vision impairment | Yes | ||
| CVI | Yes | ||
| Farsightedness | Yes (farsighted for many years—however, with further maturation, this is diminished and now she is tending toward near sightedness) | ||
| Near sightedness | Developed to some degree with further maturation (age 10) | ||
| Astigmatism | Yes | ||
| Glasses? | Transient | ||
| Will your child wear the glasses? | No | ||
| Light-gazer (stared/stares at lights) | Yes | ||
| Strabismus (occasional eye crossing) | Yes | ||
| Ptosis (drooping or falling eyelid) | No | ||
| Hearing | – | ||
| Developmental hearing impairment. Update October 2016: she has healed and passed the functional hearing tests for the first time in 5 years. She will not need a third set of permanent tubes | Started failing traditional tests at age 5 even after tubes—auditory brainstem response (ABR) performed—normal. Asymmetric, better on the right ear ABR performed with MRI at age 9 and it was normal. 2016 her final (second set) ear tubes were removed and will follow-up this to see how she does without them. Repeat ABR is necessary each year. | ||
| Sleeping | – | ||
| Did or does your child have any “prolonged sleeping problems?” | Yes (severe ages birth to age 5 waking at 1–4 a.m.). Sleeping issues decreased after the age of 5, the parents refused medication | ||
| Gastrointestinal and feeding | – | ||
| Childhood feeding problems? | Could not latch, bottle was ok, breast milk ok reflux and still regurgitates food back up in mouth and obstipation | ||
| Feeding tube | No | ||
| GERD or reflux | Yes | ||
| Oral movement difficulties | Yes | ||
| Oral drinking liquid problems (thicken liquids) | Yes | ||
| Does not seem to “getfull” | Yes | ||
| Aspiration difficulties | Yes | ||
| Is your child overweight? | Yes | ||
| Constipation problems | Yes | ||
| D | |||
| Body and skeletal | – | ||
| Teeth: did teeth come in-early? (baby teeth, including molars approximately at age 1) | NO | ||
| Feet: shape or abnormality—describe all | Short little toes, chubby/puffy, flat | ||
| Feet: (circulation) cold (abnormally cold) | Yes | ||
| Feet: size | Very small | ||
| Hand: shape or abnormality, describe all | Fifth finger clinodactyly tested by X-ray and confirmed by Mayo ClinicGenetics | ||
| Hands: puffy/pudgy | Small and toddler like | ||
| Hands: fifth finger clinodactyly? (pinky finger bends inward at the last joint) | Yes | ||
| Ankles: pronate inward/bow inward | |||
| Heart: congenital heart defect? | At/after birth it took longer for a valve to close. Murmur now not heard at age 9. Checked out ok for cardiology with recent ADNP diagnosis and ultrasound 2015 | ||
| Endocrinology and growth | – | ||
| Growth delays/“short stature” (below 25% percentile) | YES (diagnosed at the age of 3) | ||
| Growth Hormone - LOW? | Growth hormone was low around age 7 | ||
| Others | – | ||
| Has your child had “breath holding” episodes? | Started at 4 weeks old, stopped around 3 years old (ambulatory care needed and coded at hospital) | ||
| Autoimmune: did/does your child get sick often? | At young ages, high fever, RSV, kidney infection, UTI | ||
| Insensitivity to pain/high pain threshold | Yes | ||
| Temperature regulation issues | Yes | ||
| Circulation: does your child get cold hands and feet? | Yes | ||
| Toilet trained? Daytime? | In the process—76% trained | ||
| Toilet trained? Night time? | No | ||
| Hyperphagia? Excessive appetite-obsessed with eating even if not hungry… | Yes | ||
| Abnormal obsession or desires of drinking water | Yes | ||
| E. Selected p.Tyr719* ADNP-mutated children | |||
| ID | 8 | 10 | 13 |
| cDNA/nucleotide | c.2157 C>A | c.2157 C>A | c.2157 C>G |
| Protein—pchange | p.Tyr719* | p.Tyr719* | p.Tyr719* |
| Sex | Male | Female | Male |
| Birth Year | 2012 | 2014 | 2008 |
| Gross motor delay | Yes | Yes | Yes |
| Fine motor delay | Yes | Yes | Yes |
| Intellectual disability | Yes | Unknown—too young | Yes |
| Speech delay | Yes | YES | Yes |
| ASD diagnosis | Yes | unknown—too young | No |
| Brain abnormality on MRI | No | YES | Yes |
| Type of brain abnormality | n/a | Widening of ventricles, cerebral atrophy (volume loss), thinning of the corpus callosum | Frontal atrophy and some volume loss all over. Wide frontal and temporal horns. Small/fine corpus callosum |