[MIM 615 873]

(HVDAS acronym for Helsmoortel-Van der Aa syndrome, ADNP syndrome)

Rare. Loss-of-function mutation, generally de novo, of the ADNP gene (20q13.13). 

This syndromic intellectual disability syndrome combines:

-         intellectual disability 

-         motor development delay of variable severity, 

-         severe speech delay, possibly associated with orofacial dyspraxia, 

-         behavioral disorders: anxiety, obsessive-compulsive disorder, aggressive behavior, temper tantrums, attention-deficit hyperactivity and autism spectrum disorders

-         facial dysmorphism: prominent forehead with high hairline, downsliding palpebral fissures, ptosis, sometimes blepharophimosis, saddle nose and thin upper lip, deformed ear pavilions

-         sensory problems, mainly visual (refractive errors, strabismus, coloboma) and occasionally auditory, 

-         hypotonia or, rarely, hypertonia. Digestive problems are very common (gastro-oesophageal reflux, constipation).

-         minor orthopedic anomalies: clinodactyly, flat feet, exaggerated pronation of the knees and ankles

-         heart defects, short stature, skin and hormonal abnormalities and recurrent infections are also common. 

-         around 80 % of the children show very early eruption of their milk teeth, which is almost complete by the age of one year.

-         sometimes: delayed toilet training, insensitivity to pain, sleep disorders, convulsions, cerebral malformations.

Treatment: trials are underway with low doses of ketamine or NAP (the octapeptide NAPVSIPQ, which is an active extract of the NAPS protein) (davunetide) to improve behavioral disorders. 

Anesthetic implications: 

 behavioral disorders, mental retardation, echocardiography.

References : 

-        Cravero C, Gozes I, Herman C, Verloes A, Guichat V, Diaz L, Mandel A, Levine J, Cohen D.
Le syndrome ADNP (protéine neuroprotectrice dépendante de l'activité) lié à la déficience intellectuelle et aux troubles du spectre autistique: une revue de la littérature.
Neuropsychiatrie de l’Enfance et de l’Adolescence 2020; 68: 93-9

Updated: December 2023