1 - Serviço de Genética Médica, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
2 - Consulta de Genética Médica, Hospital Lusíada, Lisboa, Portugal
- Reunião Internacional EuroDysmorpho 2023 (Case Report Presentation)
We report a case of a 11-year-old (yo) girl, second child of healthy, non-consanguineous parents.
Pregnancy follow-up started at 16th week of gestation (w-o-g). Second-trimester ultrasound raised suspicion of fetal microcephaly, but confirmation in subsequent evaluations was not possible due to maternal biotype. Pregnancy was also complicated with gestational diabetes and hypertension at 33rd w-o-g.
The patient was delivered at 37th w-o-g, with an Apgar score of 9/10, a weight of 3250g (37th percentile), a length of 46,5 cm (9th percentile) but occipitofrontal circumference was not registered.
She was referred to our outpatient clinic at 16 months of age, due to developmental delay, progressive microcephaly and multifocal epilepsy. Upon examination, she presented with microbrachycephaly, fine hair, with a high anterior hairline, broad forehead, long eyelashes, hypertelorism, strabismus. Additional features included asymmetric ears, left ear with prominent helix and concha extrafold, thin upper lip vermilion, with downturned corners and bilateral single palmar crease.
At 2yo, the patient was diagnosed with choreic movements, hypermetropy and gastric reflux. Revaluation at 9 yo revealed the patient had a weight centile P<1 (-2.8 SD), intellectual disability, hypotonia, spastic paraparesis, dystonia, epilepsy and absence of language. Other dysmorphic features observed include long face, left eye ptosis, long and narrow nose, bilateral macrotia, microstomia, tongue protrusion, pointed and long chin. At 11 yo, there were no clinical changes reported.
Cranial magnetic resonance imaging revealed delayed myelination and dysgenesis of the telencephalic commissures. Extended metabolic investigation, Algelman syndrome study and microarray were normal.
A clinical exome was performed and identified a heterozygous variant of unknown significance in SPTAN1 (NM_001130438.2: c.5664A>C) gene classified as a variant of unknown significance. Pathogenic variants in this gene are associated with autosomal dominant Developmental and Epileptic Encephalopathy 5, (OMIN #613477). Segregation studies revealed that this variant was inherited from a healthy mother.
This case report emphasizes a complex clinical presentation and diagnostic odyssey in a patient with global developmental delay, microcephaly, epilepsy, movement disorder and dysmorphic features.
Palavras Chave: Developmental delay,microcephaly, epilepsy, undiagnosed cases