| Remarks |
Clinically affected; diagnosed at 5 years; symptoms onset at birth; pregnancy complicated by contractions at 30 weeks secondary to maternal urinary tract infection treated with antibiotics with subsequent positive fetal fibronectin testing; decreased fetal movement noted between 30-32 weeks gestation; born at 34 weeks via C-section due to fetal bradycardia (60-70 bpm x 6 minutes); oligohydramnios; abnormal birth weight, length, and head circumference; absence of right kidney; facial dysmorphology with overlying sutures noted at birth, originally attributed to birth position; posterior hair whorl; low posterior hair line; abnormal face shape; lagophthalmos; global developmental delay; delayed gross and fine motor development; intellectual disability; mild enlargement of the extra-axial CSF spaces in the supratentorial brain that may represent benign enlargement of the subarachnoid spaces; abnormality of peripheral nerve conduction; sleep disturbances; bruxism; non-verbal; intractable epilepsy (akinetic, myoclonus, GTC); choreoathetoid; hypotonia; difficulty walking and sitting; chronic stridor; hip subluxation; osteopenia; exaggerated cellular immune response; constipation; abnormality of cornea, retina, and optic nerve; ptosis; alacrima; anisocoria; deafness; vocal cord paralysis; laryngomalacia exacerbated by gastrointestinal reflux; GERD; daily projectile vomiting during first year of life; uncoordinated chewing and swallowing; history of elevated transaminases; elevated creatine kinases; hypohidrosis; EEG abnormality and generalized slow activity; neuroimaging showed large cerebellar vermis and abnormal brainstem morphology; MRS showed reduced brain N-acetyl aspartate levels and elevated brain choline levels; skeletal imaging showed abnormality of calvarial morphology, upper limb, pelvic girdle bone morphology, and coxa valga; genetic testing revealed maternally inherited mutation (c.1604G>A) in the NGLY1 gene resulting in p.W535X, paternally inherited mutation (c.1910delT) in the NGLY1 gene resulting in p.L637X, maternally inherited hemizygous mutation in the EDA gene resulting in R69L associated with x-linked hypohidrotic ectodermal dysplasia, paternally inherited heterozygous mutation in the RET gene resulting in R813Q associated with sporadic short-segment Hirschsprung, and paternally inherited heterozygous mutation in SIX5 gene resulting in T552M associated with cervical fistula, renal agenesis/hypoplasia/hearing loss; tracheostomy placement in 2011; Nissen and g-tube placement at 16 months old; depakote 150/150/200 mg g-tube 3 times daily; clobazam 5 mg/6.25 mg g-tube; mother (GM26597) is also in the repository; see GM26596 for fibroblast. |