SUDANESE JOURNAL OF PAEDIATRICS

2023; Vol 23, Issue No. 2

CASE REPORT

It is just not short stature

Hassan Sreenivasamurthy Rajani(1), Doddaiah Narayanappa (1), Deepa Bhat (1), Aditya Batra (1), Sathya Narayana Prashanth (1)

(1) Associate Professor, Department of Pediatrics, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India

Correspondence to:

Hassan Sreenivasamurthy Rajani

Associate Professor, Department of Pediatrics, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India.

Email: rajanihs [at] jssuni.edu.in

Received: 10 November 2022 | Accepted: 26 March 2023

How to cite this article:

Rajani HS, Narayanappa D, Bhat D, Batra A, Prashanth SN. It is just not short stature. Sudan J Paediatr. 2023;23(2):239–242.

https://doi.org/10.24911/SJP.106-1668092616

ABSTRACT

Russell-Silver syndrome, also called asymmetric dwarf dysgenesis syndrome is an uncommon genetic disorder presenting with low birth weight, failure to thrive and growth retardation (short stature), developmental delay, facial dysmorphism and hemihypertrophy. The estimated incidence is between 1 case in 3,000 to 1 case in 100,000. We are hereby reporting one such case of postnatal growth retardation with facial dysmorphism and several other features of Russell-Silver syndrome and confirmed by genetic analysis.

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KEYWORDS

Short stature; Russel-Silver syndrome.

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INTRODUCTION

Russell-Silver syndrome, also called asymmetric dwarf dysgenesis syndrome, is an uncommon genetic disorder presenting with low birth weight, failure to thrive and growth retardation (short stature), developmental delay, facial dysmorphism and hemihypertrophy. The estimated incidence is between 1 case in 3,000 to 1 case in 100,000 [1]. We are hereby reporting one such case of postnatal growth retardation with facial dysmorphism and several other features of Russell-Silver syndrome, which was not even suspected till 6 years of age, and confirmed by genetic analysis.

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CASE REPORT

A 6-year-old male child, born out of a second-degree consanguineous marriage reported with chief complaints of fever and cough. The child was short statured with facial dysmorphism. He was worked up for fever and was found to have NS1-positive dengue fever with no warning signs and was treated symptomatically. The child was then worked up for short stature and facial dysmorphism.

On physical examination, the child was a thin and short-statured child. Weight was 8 kg, height was 76 cm. Weight, height and weight for height and body mass index (BMI) were less than the third centile on World Health Organisation growth charts. The child was born small for gestational age with a birth weight of 1,500 g. The child had pseudo hydrocephalus with a head circumference (50 cm) normal for age. He was found to have a triangular face with low-set ears, a depressed nasal bridge, hypoplasia of the upper lip, high arched palate and crowding of teeth. The child had a high-pitched voice since the child started speaking. Upper to lower segment ratio was 1.24:1 with an upper segment length of 42 cm and lower segment length of 34 cm, while normal ratio is 1.1:1. The child had limb length discrepancy with left lower limb 2 cm shorter than the right lower limb. He was found to have clinodactyly (Figure 1). Echocardiography and ultrasonography (USG) of the kidney, ureter and bladder were normal. On family history, he had an elder sibling, a 10-year-old girl child with similar facial features, short stature and dysmorphism. USG abdomen and pelvis revealed absent ovaries in this girl.

The diagnosis was overlooked till 6 years of age. Based on the clinical criteria, Russell-Silver syndrome was considered by us, and parents were counselled for genetic analysis by explaining that ‘it is just not short stature.’ Molecular analysis report of methylation-specific polymerase chain reaction (MSPCR) for the MEST gene showed the absence of a paternal allele, thereby confirming the clinical diagnosis of Russell-Silver syndrome.

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DISCUSSION

Russell-Silver syndrome is a clinically as well as genetically diverse disorder of growth presenting with slow foetal growth (intrauterine growth restriction), low birth weight and growth retardation after birth, with a wide range of additional dysmorphic features [1,2] of varying severity like a triangular facial appearance with a relatively large head, a prominent forehead well appreciated on viewing from the side of the face, body asymmetry and clinodactyly of the fifth digit. Babies born have a low birth weight and often have significant feeding difficulty, growth retardation and also do not gain weight at the expected rate. It is a rare genetic disease considered an imprinting disorder. Pregnancies are unremarkable with no teratogenic exposure or significant antenatal history. Although it is thought that the insult occurs at an early age the nature of the insult being intrinsic or extrinsic is not known [3]. Overall prevalence worldwide is more than 500 cases and is reported in all age groups with no difference in incidence in males and females [1,2]. It is usually sporadic with no significant family history. Most of the affected children have normal psychomotor development but motor and/or speech delay is common [2]. In most of the affected children, a defect in chromosome 7 or 11 can be identified. These children have a perfectly normal pubertal development. There is no specific diagnostic test for Silver-Russell syndrome and the diagnosis is purely clinical (Table 1) [1,2].

Figure 1. Russell-Silver syndrome. (A) Short stature, (B) high arched palate, (C) clinodactyly, (D) and (E) relatively large head with protruding forehead.

Table 1. Netchine–Harbison clinical scoring system [1].

Clinical criteria	Definition
Feeding difficulties and/or low BMI	For BMI ≤−2 SD Score at 24 months or current use of a feeding tube or cyproheptadine appetite stimulation
SD, Standard deviation.
Small for gestational age (SGA)	Birth weight and/or birth length ≤−2 SD score for gestational age
Postnatal growth failure	Height at 24 ± 1 months ≤−2 SD score or height ≤−2 SD score below mid-parental target height
Relative macrocephaly at birth	Head circumference at birth ≥1.5 SD score above birth weight and/or length SD score
Protruding forehead/prominent forehead	Forehead projecting beyond the facial plane on a side view as a toddler (1–3 years)
Body asymmetry	Leg length discrepancy of ≥0.5 cm or arm asymmetry or leg length discrepancy of <0.5 cm with at least two other asymmetrical body parts (one non-face)

Clinically diagnosis is contemplated if the score of patients is at least four, including both prominent forehead and relative macrocephaly out of six from the above criteria (Table 1) even if all molecular tests are normal and other differential diagnoses are ruled out. The clinical scoring in this child was 5 out of 6 criteria as no documentation of head circumference at birth was available.

The diagnosis can be confirmed in around 60% of patients by molecular testing but in the remaining 40%, it is unknown [1–6]. The most frequent underlying molecular mechanisms are loss of methylation on chromosome 11p15 (11p15 LOM; seen in 30%–60% of patients) and maternal uniparental disomy for chromosome 7 (upd(7)mat; seen in ~5%–10% of patients) [1].

In this child, the molecular analysis report of MSPCR for the MEST gene showed the absence of paternal allele (MEST gene imprinting defect) with the most likely underlying molecular pathology to be maternal uniparental disomy of chromosome 7. Both the maternal and paternal alleles were detected in methylation-specific PCR-H19 on 11p15.5. Recommendations regarding the investigations, diagnosis and treatment of children with Russell-Silver syndrome are given in the published consensus guidelines [1].

Not much evidence is available on the treatment of Russell-Silver syndrome. Specific management issues include tackling significant difficulties in feeding, growth retardation in the postnatal period with no catch-up growth, premature adrenarche, precocious puberty and rapid progression of pubertal changes, recurrent hypoglycaemia, insulin resistance, body asymmetry in terms of leg length discrepancy and hemihypertrophy, orthodontic problems, sleep disorders, breathing issues and the presence of other congenital defects [1].

General treatment includes a high-calorie diet, limb lengthening/shoe lifts and growth hormone therapy [1–6]. A longitudinal study of 39 cases of Silver-Russell syndrome suggests that growth hormone therapy had no net effect on height gain. An initial response of increased height velocity was observed during treatment for 1 year with growth hormone which was followed by compensatory deceleration of height velocity with no net gain [6].

These children have normal intellect and a good life expectancy. There is not much information available in the literature about the natural history and long-term outcome of Silver-Russell syndrome [1].

Genetic counselling by a healthcare professional with experience and knowledge in the field of imprinting disorders must be considered [1].

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CONFLICT OF INTEREST

The authors declare no conflict of interest.

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FUNDING

None.

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ETHICS APPROVAL

Signed informed consent for participation and publication of medical details and photographs was obtained from the parents. The authors declare that ethics committee approval was not required for this case report.

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REFERENCES

1. Wakeling EL, Brioude F, Lokulo-Sodipe O, O’Connell SM, Salem J, Bliek J, et al.Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13(2):105–124. https://doi.org/10.1038/nrendo.2016.138. Epub 2016 Sep 2. PMID: 27585961
2. Sreedevi, Chaudhary S, Agnihotri P, B Reddy P, Nagaveni N. Russell-Silver Syndrome: a Case Report with Review of Literature. J Indian Acad Oral Med Radiol. 2011;23:73–75.
3. Perkins C, Hoang‐Xuan M. The Russell–Silver Syndrome: a case report and brief review of the literature. Pediatr Dermatol. 2002;19(6):546–9
4. Goldman V, McCoy T, Harbison M, Fragomen A, Rozbruch S. Limb lengthening in children with Russell–Silver syndrome: a comparison to other etiologies. J Child Orthop. 2013;7(2):151–6.
5. Raso M, Chiarelli F. Recent insights in Silver-Russell Syndrome. Pediatr Dimens. 2020;5(1):3–8.
6. Kumar S, Jain A, Agrawal S, Chandran S. Silver-Russell Syndrome: a case report. Cases J. 2008;1(1):304.