Dear colleague,
We received in genetic consultation on 25/07/2023 the child DELAPRAIRIE Titouan, born on 25/07/2019, accompanied by his parents and his sister, Victoire, in the context of a clinical suspicion of neurofibromatosis type I.
Family history:
Titouan is the 2nd child of a non-consanguineous couple in good health. The couple has no history of miscarriage or infertility.
His older sister Victoire, now six years old, is in good health and shows no difficulties in her learning. She is finishing her Grade 1 and is expected to start second grade next September; however, she no longer wants to return to school.
His father is 1.82 m tall and works as a salesman. He has no notable health history apart from severe asthma in childhood and atopic dermatitis. There are no notable family health histories on the paternal side.
His mother is 1.70 m tall, works as a nursery assistant in a daycare, and is also in good health. Although she mentions having little contact with her two sisters, there also seems to be no similar health history on the maternal side.
Notably, there are no family histories of intracranial or renal tumors, no mention of café-au-lait spots, nor neurofibromas among relatives.
Personal history:
Titouan was born at the end of an unremarkable pregnancy with prenatal ultrasounds considered normal. He was born eutrophic at 40 GA (BW 3500 g, BL 50 cm, HC at birth 35 cm). Apgar scores were 10/10/10, PEA +/+. There were no notable pathologies during the neonatal period.
Regarding his psychomotor development, he pronounced "daddy" and "mommy" at 13 months, constructed his first subject-verb-object sentences around 24 months, but still has some difficulties articulating certain consonants.
Motor-wise, he rolled over at around seven months, took his first steps at 15 months. He currently has some difficulties with fine motor skills, warranting weekly psychomotor therapy, particularly for writing and drawing.
The first concerns arose at 26 months when the daycare mentioned a rather solitary behavior associated with significant agitation and difficulties focusing on various activities.
He was seen in this context by Dr. PLOU, the family's treating physician, who referred Titouan to us today, alerted by multiple café-au-lait spots.
Clinical examination:
Titouan weighs 15 kg (-1 DS), measures 105 cm (+1 DS), and has a HC of 55 cm (average). He is a smiling child but appears uncooperative and agitated during the examination. His osteotendinous and cutaneous-plantar reflexes are normal. The walking examination is normal. Morphologically, we find few particularities apart from a slightly hollow palate and left occipital plagiocephaly. On cutaneous examination, we find seven centimeter-sized café-au-lait spots on the trunk and the posterior aspect of the thighs, without neurofibromas or lentigines. The spinal statics seem normal. Heart sounds are regular without murmurs on auscultation, and the abdomen is soft, depressible, and painless without palpable masses.
Initial explorations:
Given the clinical suspicion of neurofibromatosis type I, we plan to perform a whole-body MRI under sedation in six months to avoid missing an optic pathway glioma and a pheochromocytoma, although rarely observed at this age.
We also request an ophthalmological examination to search for Lisch nodules.
On the genetic level, we propose initial investigations by studying the NF1 gene, whose pathogenic variations cause neurofibromatosis type I. This study is outsourced to APHP.
In summary:
Titouan is a four-year-old child presenting an association of behavioral disorders with some difficulties in fine motor skills, as well as seven café-au-lait spots clinically suggesting a diagnosis of neurofibromatosis type I. We find no evocative elements of similar family histories, but we explain that this pathology, which is autosomal dominant, occurs in a large part of cases de novo. We propose in this context the study of the NF1 gene in Titouan. This study could take several months, and we will not fail to contact the family for the results report.
We remain at your disposal for any further information,
Best regards,