Objective@#To
report a
family diagnosed with Allan-Herndon-Dudley
syndrome (AHDS) due to SLC16A2
gene mutation and to summarize the
phenotypes,
genotypes,
diagnosis,
treatment, and
prognosis.@*
Methods@#The clinical features of a
family of AHDS diagnosed in Xiangya
Hospital of Central South
University in November 2017 were analyzed. Related
literature was searched at
Online Mendelian Inheritance in Man (
OMIM),
PubMed, CNKI and Wanfang database (from the establishment of databases to June 2018) by using "Allan-Herndon-Dudley
syndrome" , and "AHDS" as
keywords and the
case reports from April 2013 to June 2018 were reviewed.@*Results@#The proband was a boy
aged 8 months
who presented with global developmental retardation, inability to hold up the
head, disability to sit independently or grab, no
language development, elongated
face, big
ears,
esotropia,
scoliosis,
hypotonia in the trunk, hypertonia in
extremities, and
hyperreflexia.
Brain magnetic resonance imaging (MRI) showed widening of the extracerebral space and delayed myelination.
Thyroid function tests revealed increased FT3, decreased FT4 and normal TSH.
Whole exome sequencing (WES) revealed the SLC16A2
gene c.431-1 (IVS1) G>C hemizygous
mutation. The
infant's
mother and
grandmother are carriers, but whose
father had no related
mutation. One uncle from maternal side had severe psychomotor retardation as well as
dystonia and died at one year of age with unknown
etiology. A total of 97 articles were retrieved in which 19
case reports were reviewed. Forty-two cases (22 from 8
families and 20 sporadic) were reported. Among these 42 cases (all
males), all of them presented with moderate to severe
cognitive dysfunction, 15 with seizures; 36 were bedridden, only 4 could walk; 31 had no
language development, 2 could speak sentences, 4 could speak few words, 1 had babbling
sounds. Furthermore,16 had
microcephaly, 18 had facial dysmorphism, 6 had
esotropia, 2 had
hearing loss,14 had
scoliosis, 11 had
joint contracture, 30 had low
body weight/
muscle wasting, 37 had
hypotonia in trunk or
extremities, 32 had progressive
spastic paraplegia or hypertonia. In terms of
thyroid function, 33 had abnormal results, within whom 30 had increased T3, 25 had decreased T4 and 3 had increased TSH.
Brain MRI showed delayed myelination in 22 cases, within which one normalized with development. Genetic tests showed that 31 had
missense mutation (14 sporadic), 5 had
deletion mutation (3 sporadic, and 1 due to
frameshift mutation), 5 had
insertion mutation (2 sporadic), and 1 had repeated
mutation. The
prognosis was poor as
patients often died of recurrent
respiratory tract infection.@*Conclusions@#The main clinical manifestations of AHDS are severe global developmental retardation,
hypotonia,
spastic paraplegia, abnormal
serum levels of
thyroid hormone and delayed
brain myelination. SLC16A2 c. 431-1 (IVS1) G > C
mutation is accountable for this
disease.