CORRESPONDENCE

Clinical Features of Patients With The specific relationship between genotype and
phenotype in 7p22.1 deletion is still unknown. The
7p22.1 Microdeletion deleted region in index case contained 36 genes,
including RNF216, AIMP2, RAC1, PMS2 and ACTB,
which are known pathogenic genes. Mutations in
With the advent of comparative genomic hybridization RNF216, AIMP2, RAC1 and ACTB are associated with
(CGH) technology, more patients with microduplications intellectual disability [1-5]. The expression levels of ACTB
or micro deletions are being reported. Herein, we report an are linearly correlated with the ACTB gene copy number
11-year-old girl with 7p22.1 microdeletion who presented and influence the amount of β-actin, which is involved in
with short stature and intellectual disability. She was the cell motility and expressed in all eukaryotic cells [1,2].
second born child to non-consanguineous parents, born Thus, the haploinsufficiency of ACTB may be
at full term with a birthweight of 2 kg. Ventricular septal accountable for intellectual disability and other clinical
defect and patent foramen ovale were detected after birth features in 7q22.1 microdeletion [2]. Postnatal growth
and cardiac surgery was undertaken at one year of age retardation, high forehead, hypertelorism, arched
(weight 7 kg). At four years of age, she was detected with eyebrows, broad nose with large tip, hypoplastic
intellectual disability and short stature (height of 87 cm) scapulas, and congenital heart defects in index case were
with a normal karyotype (46,XX). consistent with the features of ACTB gene deficiency.
However, ACTB gene was not deleted in few cases who
At 11 years, her weight was 31.3 kg (about -1 SD) showed intellectual disability, implying that other genes
height 134.5 cm (<2 SD), with distinctive facial features (e.g., RAC1 gene) or even non-coding RNA coded in this
including long face, high forehead, arched eyebrows, region may contribute to the clinical features of this rare
long eyelashes, flat nose bridge, broad nose, upturned condition.
lip, downturned corners of the mouth and pointed chin.
Small brown pigmentation, snaggle teeth, sagging In summary, 7p22.1 microdeletion syndrome should
shoulders and shoulder girdle muscle bulk, scar on the be considered in patients with intellectual disability,
chest wall, flexion of the left thumb (contracture), distinctive facial features, microcephaly, short stature,
clinodactyly and abnormal dermatogly-phics were also inguinal hernia, hypotonia, and congenital heart disease
noted with Tanner stage 4 breast development. Wechsler and confirmed with genetic testing.
intelligence scale showed intellectual disability with a Contributors: CCZ: conceived the study; HYL and JXF:
score of 56. manuscript writing and literatures review. All authors approved
the final manuscript.
Laboratory data showed hypertriglyceridemia (3.64 Funding: National Natural Science Foundation (81170787 &
mmol/L). The levels of follicle stimulating hormone, 81371215) and Zhejiang Provincial Program for the Cultivation
luteinizing hormone, prolactin, progesterone and of High-Level Innovative Health Talents (2014);
estradiol were consistent with sexual development. The Competing interest: None stated.
level of insulin-like growth factor 1, insulin like growth
HAN-YUE LI1, JING-XIA FANG2, CHAO-CHUN ZOU1*
factor binding protein 3, corticotrophin, cortisol, liver Department of 1Endocrinology,
function, renal function and thyroid function were in The Children’s Hospital, Zhejiang University School of
normal range. An abdominal ultrasound was normal. Medicine, National Clinical Research Center for Child Health,
Copy number variation (CNV) analysis (MyGenostics China and 2Pediatrics,
Gene Technology Co., Ltd. China) was performed and a Yongkang Fangda Ruijin Hospital, Jinhua
*zcc14@[Link]
1.673 Mb microdeletion (chr7: 5 147 686-6 820 998) at
chromosome 7p22.1 was found. No similar deletion was REFERENCES
noted from her parents by CNV analysis and her parents
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A, Palladino T, et al. Refinement of the critical 7p22.1
About 30 cases with 7p22.1 microdeletion have been deletion region: haploin sufficiency of ACTB is the cause of
earlier reported [1,2]. The common clinical features in the 7p22.1 microdeletion-related developmental disorders.
these patients included intellectual disability (58.3%), Eur J Med Genet. 2018;61:248-52.
distinctive facial features (44%), short stature (33.3%), 2. Shimojima K, Narai S, Togawa M, Doumoto T, Sangu N,
Vanakker OM, et al. 7p22.1 microdeletions involving
microcephaly (22.2%), hernia (14.8%), hypotonia (14.8%),
ACTB associated with developmental delay, short stature,
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bilateral radial abnormalities, PFO, pulmonary artery 3. Husain N, Yuan Q, Yen YC, Pletnikova O, Sally DQ,
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with Gordon Holmes syndrome lead to synaptic and neurodevelopmental disorder with microcephaly, seizures,
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Vinblastine-induced Acral absent in our child [2]. Moreover, her red blood cell
indices were normocytic and normochromic, ruling out
Hyperpigmentation this possibility. Drug-induced acral hyperpigmentation
was considered after ruling out other differentials and
vinblastine was discontinued, following which the
hyperpigmentation faded over a period of 3 weeks, but
A 5-year-old girl, diagnosed with multi-system did not disappear completely.
langerhans cell histiocytosis (bone, liver, bone marrow
Vinca alkaloids are notorious for causing extra-
and pituitary involvement), was started on induction
vasation injury [4]. Supravenous hyperpigmentation has
chemotherapy (weekly cycles of vinblastine/
been reported with the ABVD regimen which includes
prednisolone for 12 weeks). Two months later, she
vinblastine (however, the causative drug was not
developed progressive bluish-black discolouration over
implicated) [5]. Vinorelbine, a vinca alkaloid, in high doses
the nose and fingertips along with darkening of the nail
is known to cause acral erythema [6]. Although drug-
beds without any itching, pain, redness, numbness,
induced hyperpigmentation is responsible for 10-20%
trauma or sun exposure.
cases of acquired hyperpigmentation [2], it has not been
Several differentials were considered, Chikungunya reported with either vinblastine or prednisolone. Possible
fever is well reported for causing an acute, brownish- mechanisms of drug induced acral hyperpigmentation
black, centrofacial hyperpigmentation [1]. It can persist
for three to six months after resolution of infection [1].
However, our child had no fever, arthralgia or cytopenias
to suggest an infectious aetiology. Addisonian
hyperpigmentation, which commonly involves mucous
membranes, flexures, palmar and plantar creases, the
areola, genitalia and pressure points (elbows and knees),
was ruled out clinically, as well as by the absence of
hyponatremia, hyperkalemia and acidosis [1].
Hyperpigmentation in thyroid disorders also has a similar
distribution as in Addison disease [2]; however, the
thyroid function test was normal. Exogenous ochronosis,
secondary to topical hydroquinone use, responsible for
bluish-black hyperpigmentation of the sun-exposed areas
of the face, was also ruled out as there was no history of
such application; neither was henna applied locally [1,2].
She had no preceding redness, scaling, pain, injury or
cutaneous eruptions to suggest post-inflammatory
hyperpigmentation [3]. Acanthosis nigricans, although
classically noted over the nape of the neck, axilla and
groin, can also develop over the face [4]. However, our
child had neither hyperglycemia nor obesity and the
lesion in question lacked the characteristic velvety
thickening of acanthosis nigricans [3]. The involvement
of distal phalanges, interphalangeal joints and oral
mucosa, characteristic of Vitamin B12 deficiency, was Fig.1

INDIAN PEDIATRICS 581 VOLUME 57__JUNE 15, 2020