We are sharing this information in the hopes of finding more patients and for ensuring the best care and treatment for Charlotte and Cooper.

 

Our joyful daughter Charlotte and cuddly son Cooper are suffering from a rare undiagnosed disease.  They both have a variant on their FAM177A1 gene that we highly suspect has caused their disease.  We know of a few other patient with this variant who have similar symptoms and disruption of the FAM177A1 gene but we do not yet know the function of FAM177A1. Charlotte and Cooper have a neuro-typically developing older brother and there is no history of similar disease in our families’ histories.

Gradient

Cooper is a Caucasian male with global developmental delay, intellectual disability, autistic behaviors, macrocephaly, axial hypotonia, congenital bilateral cataracts, and seizures onset age 6.

 

Cooper was born at 37-weeks gestational age via repeat C-section weighing just over 8 lbs. The pregnancy was complicated by polyhydramnios, maternal thrombocytopenia, and fetal macrosomia. Mom developed HELLP syndrome after delivery but made a full recovery. As a neonate, Cooper was fussy and found to have reflux. His growth was normal with the exception of increased occipital-frontal circumference. Developmentally, he had low muscle tone and had a similar developmental presentation to his sister. In addition, bilateral congenital cataracts were noted and Cooper had surgery to remove the cataracts prior to his 1st birthday. Cooper went on to have evaluations by ophthalmology, optometry, a naturopath, neurodevelopmental, and biochemical geneticists—all of which failed to provide a discrete and unifying diagnosis. Cooper also had an expanded metabolic screening and TORCH titers.

 

He received OT/PT/speech therapy services beginning at 6 months of age. He received an autism diagnosis as a preschooler and subsequently began ABA therapy.

 

Cooper developed seizures at age 6 (tonic-clonic and complex partial).  His seizures are minimally controlled with medication. His seizures continued on a Keto diet. 

 

Additional features include:

  • MRI Brain (2016): unremarkable

  • Unusual gate

  • History or period unexplained limping; possible juvenile idopathic arthritis

  • Behavioral abnormalities: aggressive behaviors, destruction of property

  • Autistic behaviors: communication and social delays, flapping, tiptoeing, high interest in loud noises (vacuums, blenders)

  • Speech/language: absent expressive language, uses a few signs and gestures

  • Single transverse palmar crease (bilateral)

  • Clinodactyly of the 5th toe

  • 2–3 toe syndactyly

  • Strong affinity for water

Gradient

Charlotte is a Caucasian female with global developmental delay, intellectual disability, autistic behaviors, macrocephaly (large head size), axial hypotonia (low muscle tone), hyperreflexia (over-active reflexes), gait abnormality (unusual walking pattern), and seizures onset at age 12.

 

Charlotte was born at term weighing 8 lbs, 13 oz. The pregnancy and delivery were uncomplicated. She was a content infant. Concerns about her development began early in infancy with hypotonia and gross motor delays. This progressed to include speech/language delays as well. An extensive investigation for underlying cause of developmental delay was initiated and she was evaluated via genetics, biochemical genetics, ophthalmology, neurology, neurodevelopmental, speech therapy, occupational therapy, and physical therapy. Additionally, she had two brain MRI scans at ages 2 and 3 that showed delayed myelination but otherwise appeared normal. Absence seizure activity was suspected at a young age but EEG results were normal. Charlotte developed tonic-clonic seizures at age 12 but has had infrequent seizures since.

 

Extensive early lab testing was normal for the following: CK, high resolution chromosomes, metabolic screening, urine organic acids, acylcarnitine, plasma organic acids, long chain fatty acids, mucopolysaccharides, Fragile X, Prader-Willi, Angelman’s Syndrome, Krabbe’s, electrolytes, ammonia, lactic acid, pyruvate, isoelectric carbohydrate deficient transferrin, urine oligosaccharides[KR1] , urine metabolic screening, acetyl carnitine profile, metachromatic leukodystrophy, GM-1 gangliosidosos, oligonucleotide array comparative genomic hybridization, and chromosome microarray.

 

Charlotte has been generally healthy except for a few respiratory illnesses and urinary tract infections (renal ultrasound normal). With illness, there is a clear regression in terms of development. Fortunately, she regains those losses and her general developmental trajectory has been steady.

 

Charlotte has received extensive occupational, physical, and speech therapy. She has made gradual progress in all areas of development but remains significantly delayed. She was diagnosed with Autism at around age 8 and began ABA therapy. In addition to significant social and communication impairment, autistic behaviors that have come and gone included flapping, lip biting, repetitively touching forehead with right fist, and echolalia.

 

She has had periods of extreme irritability and mood swings and has been followed by a psychiatrist. She has diagnosis of ADHD and Disruptive Behavior Disorder.

Charlotte has a history of sleep disturbance (early waking) but became a better sleeper around age 11.

 

In 2018 Charlotte had surgery to lengthen her hamstrings which had contractures and were consequently stuck in a shortened length causing her to walk in a crouched position with knees touching.

 

Here is a link to a video of Charlotte walking that shows her unusual gait/walking pattern before surgery. 

 

Additional features include:

  • Gait: walking with high energy posture, prior to surgery she was flexed at waist and knees held together; after surgery still has compromised balance, toe drag

  • Cogwheeling rigidity (tension in a muscle that gives way in little jerks when the muscle is passively stretched), particularly in arms

  • Autistic behaviors: social and communication delays, flapping, lip biting, repetitively touching forehead with right fist, echolalia

  • Speech/Language: speaks approx. large vocabulary but has narrow interests; can put several words together but usually speaks in short phrases; difficulty articulating.

  • Disruptive behaviors: elopement, impulsivity, whining, screeching

  • Upslanted palpebral fissures

  • Single transverse palmar crease (unilateral)

  • Clinodactyly of the 5th toe

  • 2–3 toe syndactyly

  • Strong affinity for water