PHENOTYPIC VARIATIONS IN WOLFHIRSCHHORN
SYNDROME
Sukarova-Angelovska E, Kocova M, Sabolich V, Palcevska S, Angelkova N
*Corresponding Author: Doz. Elena Sukarova-Angelovska, Pediatric Clinic, Medical Faculty, Vodnjanska 17,
1000 Skopje, Republic of Macedonia. Tel.: +389-70358582. Fax: +389-22439301. E-mail: Esukarova@doctor.com
page: 23
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RESULTS
Patient 1. An infant boy at the age of 24 days was
admitted to the clinic because of asphyxia, hypotonia,
poor sucking and failure to thrive. He was the first
child of young, unrelated parents. Intrauterine growth
retardation was noticed during the fourth month of
pregnancy. Delivery was at term, birth weight was
2200 gr, birth length 45 cm. The neonate was hypotonic,
had frequent apneic episodes and poor sucking.
Dysmorphic profile was estimated as severe [+++]
according to the presence and severity of dysmorphic
features (Table 1). Evaluation of the heart revealed a minor atrial septal defect (ASD). Ultrasonography
of the kidneys showed agenesia of the left
kidney and hypoplasia of the right kidney. Serum
urea and creatinine were above the upper limit.
At the age of 2 years, the child had an intestinal
obstruction due to a malrotation and underwent
surgery. Seizures started at the age of 1.5 months,
and had tonic-clonic characteristics, with severe,
long-lasting outbursts frequently leading to epileptic
status; therefore, antiepileptic therapy was
introduced. At the age of 4 years he was not able
to walk without support and had autistic behavior.
Chromosome analysis revealed a cytogenetically
visible deletion of the short arm of chromosome
4: 46,XY,del(4)(p15.3).
Patient 2. A 3-month baby was referred to our
clinic because of facial dysmorphism. She was the
second child in a family of healthy and non consanguinous
parents. The pregnancy was uneventful;
the delivery was after 41 weeks of gestation, birth
weight was 2800 gr, birth length was 49 cm. The
child had asphyxia and was resuscitated. At the time
of the examination the baby had failed to thrive
and did not achieve developmental milestones. She
had facial dysmorphism ascertained as severe. Additional
dysmorphic features included transversal
crease on the left hand, club feet and joint stiffness of
both legs; a small umbilical hernia was also noticed.
Ultrasonography of the heart revealed a congenital
heart defect, an ASD with a dilated ascendant
aorta. The lateral ventricles of the brain were slightly
enlarged. The karyotype was 46,XX,del(4)(p16.1)
(Figure 2). We have no data if this child had convulsions
afterwards as she was lost of follow-up.
Patient 3. The patient was a 6-month-old girl
and was the first child born to unrelated parents.
She was born after a normal pregnancy and delivery,
with birth weight of 2350 gr and length 47 cm.
Motor delay was noticed from the fourth month
of age. She had characteristic facial dysmorphism
estimated as severe [+++]. Cleft of the palate was
along the hard and soft palate. The sacral sinus was
deep. At the age of 4 months she developed seizures
(first febrile, afterwards afebrile and generalized).
The convulsions were frequent, prolonged
and difficult to manage, requiring a combination
of several anticonvulsant drugs. The karyotype
was 46,XX,del(4)(p16.1).
Patient 4. A female patient, aged 16 months,
was the second child of unrelated healthy parents. Their first child had been operated on because of an
urethral obstruction but he was otherwise normal.
The mother experienced vaginal bleeding during the
first trimester of the pregnancy. Delivery was before
term and the umbilical cord was wrapped around
the baby’s neck; her birth weight was 2340 gr, birth
length 44 cm. She had minor developmental delay,
first thought to be caused by the neonatal asphyxia.
She was estimated to have a moderate [++] phenotype.
She had a unilateral cleft lip, notched left
nostril, small allae nasi, bat-like ears. Both kidneys
were hypoplastic. The karyotype was normal. The
microdeletion of 4p was detected by FISH. At the
age of 3 years, she developed clonic-tonic seizures.
Despite combined anticonvulsant therapy, her epilepsy
remains resistant. After the start of the seizures,
her motor and mental abilities started to deteriorate;
she thus lost most of her motor abilities. Therefore,
the estimation of her motor delay in this study was
estimated to be before occurrence of the seizures.
Patient 5. This is the first child resulting from
eigh in vitro fertilization (IVF) attempts by healthy
parents. The fetus had prenatal growth delay. He was
born pre term, at week 35 of gestation, and was small
for gestational age; birth weight was 1660 gr and
birth length 40 cm. Because of immaturity, feeding
problems and respiratory distress syndrome, the baby
remained in an incubator for 2 months. Dysmorphic
profile was considered as minor [+] due to the presence
of only a few dysmorphic features, and smaller
central nervous system (CNS) changes. There was
a cardiac defect showing foramen ovale and open
ductus arteriosus. Left heart catheterization revealed
multiple aortic-venous pulmonary communications,
as well as truncus bicaroticus. During the following
months, the baby achieved more developmental
skills. However, some discharges of myoclonal character
on EEG (electroencephalography) were noticed
without visible seizures. The karyotype was normal.
Using FISH, chromosome 4p showed 46,XY,ish
del(4)(p16.3) (Figure 3).
Patient 6. The proband was a 16-month-old boy
referred because of developmental delay. The pregnancy
was uneventful; however, diminished fetal
proportions were noticed on ultrasonography during
the second trimester. The delivery was at term, birth
weight was 2900 gr, birth length 49 cm. Psychomotor
delay was evident after age 6 months. He started to
walk at the age of 2 years, pronounced first words at
3 years; however, at the age of 6 years, he still had
a poor vocabulary. His motor and mental disability
was estimated as moderate according the Griffiths
scale. The child had a broad forehead, prominent
glabella and prominent orbital ridges that was suggestive
of WHS. Examination of other organs and
systems were normal. At the age of 3 years, the child
was given anticonvulsant therapy because of convulsions.
The karyotype was 46,XY,del(4)(p16.1)
[30%]/46,XY[70%].
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