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Participant 046

On this page, you will find information about a UDN participant.

Sharing information on this website is not a requirement of UDN participation. Only descriptions about participants who give explicit consent will appear here. While these participant pages are helpful to understand our participants’ stories, they do not begin to describe their diagnostic odysseys. A special thank you goes out to our participants and their families for sharing their experiences.


Female, age 10, with developmental delay, joint contractures, seizures, and multiple birth defects caused by a change in the ZC4H2 gene

Date of Report

Aug 24, 2021


At birth, the participant was noticed to have a small head (microcephaly), overlapping fingers, cleft palate, increased muscle tone (hypertonia), rocker bottom feet, abnormal creases on her hands, long and slender fingers, partially dislocated hips (bilateral hip subluxations), and joint contractures. At the age of 3, she had a muscle biopsy that showed a mitochondrial deficiency (mitochondrial complex Il deficiency).

Over time, the participant started having seizures, which are currently being controlled with medication. She also has kidney problems (renal tubular acidosis), acid reflux, hearing impairment in her left ear, and some vision issues (Duane anomaly, cortical visual impairment).

Developmentally, she was delayed in meeting her milestones (global developmental delay). She started speaking around the age of 3 and currently uses 2-3 word phrases.

Symptoms / Signs
  • Global developmental delay
  • Seizures
  • Short stature
  • Difficulty growing (failure to thrive)
  • Increased and decreased muscle tone (hypertonia, hypotonia)
  • Joint contractures
  • Muscle spasms (clonus)
  • Prominent back of head (prominent occiput)
  • Neck twisted to one side (torticollis)
  • Protruding forehead (frontal bossing)
  • Cross-eyed (strabismus)
  • Astigmatism
  • Difficulty with eye movements (Duane anomaly)
  • Visual impairment (cortical)
  • Reduced vision in one eye (amblyopia)
  • Weakness of eye muscle (restrictive external ophthalmoplegia)
  • Dropped upper eyelid (ptosis)
  • Eye turned inward (esotropia)
  • Nosebleeds (epistaxis)
  • Short nose
  • Hearing impairment
  • Full cheeks
  • Cleft palate
  • Downturned corners of mouth
  • Small jaw (micrognathia)
  • Feeding difficulties
  • Gastroparesis
  • Excessive thirst (polydipsia)
  • Acid reflux (gastroesophageal reflux)
  • Tear in membrane of esophagus to stomach (Mallory-Weiss tear)
  • Hiatal hernia
  • Kidney problems (renal tubular acidosis)
  • Low blood sugar (hypoglycemia)
  • Sleep apnea
  • Curved spine (scoliosis, kyphoscoliosis)
  • Underdeveloped hip joints (hip dysplasia)
  • Overlapping fingers
  • Long slender fingers (arachnodactyly)
  • Tapered finger
  • Stiff and tight lower limbs (lower limb spasticity)
  • Rocker bottom feet
  • Clubfoot (talipes equinovarus)
Current Treatments
  • Albuterol, QVAR- breathing problems
  • Alpha lipoic acid- low blood sugar
  • Bethanechol
  • Bicitra – acidosis
  • Cholecalciferol
  • Cromolyn, Erythromycin, Omeprazole- acid reflux
  • Diastat, Keppra, Phenobarbital- seizures
  • EpiPen- allergic reactions
  • Gastrocrom- inflammation
  • Riboflavin
Prior Treatments
  • Cleft palate repair
  • G-tube- feeding difficulties
Considered treatments
Previously Considered Diagnoses
  • Arthrogryposis multiplex congenital
  • Beals syndrome
  • Congenital contractural arachnodactyly
  • Microdeletion/duplication syndrome
  • Mitochondrial condition
  • Myotonic dystrophy
  • Prader-Willi syndrome
  • Sheldon-Hall syndrome
  • Single gene disorder (exome sequencing nondiagnostic)
Other Photographs
Genetic Variants of Interest

In 2020, clinicians and researchers identified the following genetic change to be causing the participant’s symptoms:

Inheritance Pattern
Position (hg19)
DNA Change
Protein Change

If this participant sounds like you or someone you know, please contact us!


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