Vocal cord paralysis in association with 9q34 duplication

Abstract

Micrognathia Prominent ears Truncal hypotonia Stridor Vocal cord paralysis Eczema Short clinical summaryThe proband was a male born at 40 + 6 weeks of gestation after an uneventful pregnancy. His birth weight was 4100 g (75th centile), his length was 53 cm (75th centile) and his head circumference was measured to be 35.8 cm (50th centile). He was the third child of healthy, nonconsanguineous Irish parents. The family history was unremarkable.On day 2, he presented with a continuous stridor and he was referred for ear, nose and throat (ENT) review. Flexible laryngoscopy performed at the age of 3 days revealed bilateral vocal cord paralysis (VCP). On admission he was assessed by a neurologist who felt he had significant head lag and truncal hypotonia. A number of dysmorphic features were noted including long digits, micrognathia and a small phallus. He had cortisol levels checked on two occasions (because of a small phallus) and these were both low (40 and 90 nmol/l, respectively). However, adrenocorticotropic hormone and luteinizingreleasing hormone stimulation testing was normal and on review the phallus size was felt to be within normal limits. He was referred for a genetic review at the age of 6 months. The physical examination showed only prominent ears and eczema (Fig. 1). He was otherwise nondysmorphic. His growth parameters were appropriate for his age. His hypotonia had improved although mild delay in his gross motor skills was noted.At 9 months his delay in gross motor skills was more obvious, he still was not able to sit unsupported. Review by the ENT team noted improvement of the vocal cords. Despite the VCP the baby's airway remained satisfactory and an airway intervention such as tracheostomy was not needed.At the age of 11 months he was babbling and he had about six to seven words. He was able to hold a spoon and feed himself. He did not crawl and did not pull himself up to stand. An examination at 21 months of age showed complete recovery of the VCP. At 2 years of age, his growth parameters were as follows: weight 13.2 kg (50-75th centile), occipital frontal head circumference 50 cm (50th centile) and height 92 cm (91st centile). An MRI brain scan showed an arachnoid cyst at the inferior of left cerebellopontine angle with marginal displacement of adjacent cerebellum and brainstem. His echocardiogram was normal.

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

“…A 9q34 duplication syndrome (9q34 DS) has been reported [10], involving both interstitial [11][12][13][14] and terminal [1,10,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] duplications, with different sizes. The associated manifestations include initial poor feeding and thriving, hypotonia, DD, mostly affecting speech and language, ID, craniofacial dysmorphisms and other musculoskeletal anomalies.…”

Evaluation of a patient with classical Ehlers‐Danlos syndrome due to a 9q34 duplication affecting COL5A1

“…). cEDS phenotype has not been reported in three of five cases with a pure 9q34 duplication encompassing COL5A1 (Mizuno et al ; Gadancheva et al ; Natera‐de Benito et al ).…”

“…Multi-exon deletions and duplications in COL5A1 are expected to strongly contribute to the pathogenesis of cEDS. Only five cases with pure distal duplication of 9q34 have been reported (Mizuno et al 2011;Singh et al 2012;Gadancheva et al 2014;Natera-de Benito et al 2015) (Fig. 3).…”