Endocrine Abstracts

JOINT3607

Introduction: Filippi syndrome (FS) is a rare autosomal recessive disorder characterized by microcephaly, growth retardation, syndactyly, intellectual disability and dysmorphia. With only forty cases reported globally, diagnosis remains challenging.

Clinical Case: A 3-year-old girl, born full-term with fetal growth restriction (weight -2.26SDS, length -1.89SDS, head circumference -0.41SDS - Fenton 2013), was referenced to Pediatric Endocrinology due to short stature. There was no parental consanguinity and family history was unremarkable. Medical history included neonatal jaundice, ventricular septal defect and patent foramen ovale (spontaneously resolved by 1-year-old), umbilical hernia repair, recurrent otitis media and adenoidectomy. Dysmorphic features comprise high nasal bridge, thin alae nasi, square chin, clinodactyly of the fifth fingers bilaterally, and syndactyly of the second/third and third/fourth toes bilaterally. She also presented with microcephaly and intellectual development disorder at 6-years-old (Wechsler Intelligence Scale for Children III with Intelligence Quotient of 65, classification: very low). At 5 years-old she had height -2.72SD, weight -1.72SD, body mass index 0.15SD, family target height -1.82SD, bone age (BA) of 3-years-old and growth velocity of 8cm in the last year. Over time, growth slowed down, reaching -3.30SDS at 16-years-old. Thelarche and pubarche occurred at 10-years-old but menarche had never occurred. A whole exome study was carried out at 11-years-old, detecting decompound heterozygous variants in the CKAP2L gene (c.1092_1093del p.(Gln364Hisfs16) and c.1534_1537del p.(Lys512Hisfs13)), both classified as likely pathogenic, and FS was diagnosed. Analytical study excluded chronic disease. Endocrinological study showed: Follicle-stimulating hormone 7.55IU/l, Luteinizing hormone 3.26IU/l, estradiol 54.6 pmol/L (normal range 25.6-220.3). Growth hormone, cortisol and thyroid deficiency were excluded. Brain magnetic resonance was unremarkable. Abdominal-pelvic ultrasounds revealed hypoplastic uterus and small ovaries. Her last BA showed a delay of 1year (at 14-years-old). Currently, at 17-years-old, Tanner Stage M3P3, she remains amenorrheic, and ethinylestradiol was initiated.

Discussion: The authors present a case of FS, an extremely rare genetic disorder, emphasizing it as a cause of short stature and primary amenorrhea. Authors should share the evolution of these cases, to broaden the clinical spectrum of FS. This girl presented with delayed puberty although there are other cases described with precocious puberty. Although there is an association with neurologic abnormalities, seizures and growth hormone deficiency, they were not presented in this case. Early diagnosis can enable a personalized and timely approach to the patient’s reproductive health, and also metabolic and bone well-being.