The subjects of this study are two sisters of Arab Muslim origin and their parents are entirely healthy first-degree cousins with no visual or neurological complaints. Patient I-1 was born prematurely at 35 weeks gestation and failure to thrive was a problem since birth. At 2 months of age, she was also noted to have truncal hypotonia that was replaced by multiple episodes of hypertonia and opisthotonic posturing. Furthermore, she had a weak cry and abnormal eye pursuits. An initial echocardiography and ophthalmological examinations performed at that time were unremarkable. Metabolic investigations revealed elevated serum alanine and lactate levels, but a normal cerebrospinal fluid (CSF) lactate concentration. Disease progression was marked by a persisting failure to thrive with severe neurodevelopmental delay, but brain MRI was normal. The patient subsequently developed a progressive, non-obstructive, generalised hypertrophic cardiomyopathy, in the absence of overt heart failure. The patient died at 10 months of age following an apnoeic episode.
Case#: Speigel Patient I-1, onset at birth, death at 10mo
DiseaseAssertion: Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy
FamilyInfo: Parents are healthy first-degree cousins with no visual or neurological complaints. Both parents were heterozygous for this OPA1 variant. Their optic discs did not look pale on dilated fundus examination and optical coherence tomography (OCT) imaging did not show any subclinical thinning of the retinal nerve fibre layer. The parents have two clinically unaffected sons who were 14 and 11 years old when last reviewed in clinic. The older son is heterozygous for the c.1601T>G OPA1 variant, whereas the other son only carries the wild-type OPA1 allele.
CasePresentingHPOs: HP:0001622, HP:0001531, HP:0008936, HP:0001276, HP:0002179, HP:0001612, HP:0000617, HP:0031964, HP:0012758, HP:0001639, HP:0002104
CaseHPOFreeText: elevated lactate levels, but a normal cerebrospinal fluid (CSF) lactate concentration. progressive, non-obstructive, generalised hypertrophic cardiomyopathy,
CaseNotHPOs: HP:0001635
CaseNotHPOFreeText: abnormal brain MRI
GenotypingMethod: genome-wide autozygosity mapping and next-generation exome sequencing
PreviouslyPublished: n/a
Variant: OPA1 NM_015560.2 c.1601T>G p.Leu534Arg
ClinVar:
CAID: CA357235
SupplementalData: n/a