Alazami syndrome: Report of three Indian patients with phenotypic spectrum from adolescence to adulthood

Abstract

Alazami syndrome (ALAZS) (MIM 615071) is a rare autosomal recessive disorder characterized by short stature, dysmorphic facial features, developmental delay, and impaired intellect. It was first reported in a Saudi Arabian family in 2012. Three Indian patients affected with ALAZS, one boy aged 13 years and other two sisters in their 40s are presented. These patients had few unreported dysmorphic facial features: high arched eyebrows and dental overcrowding. No microcephaly was noted in the sisters. One of the sisters did not have short stature. The boy also presented with unilateral buphthalmos of left eye. All three of them have been identified to harbor novel variants in LARP7.

Further phenotypic delineation of Alazami syndrome

“…Initially, Hollink et al (2016) reported on two patients with normal birth growth parameters but developed failure to thrive at a later age. Thereafter, the description of these similar characteristics was reported in other studies (Bajafar et al, 2019; Das et al, 2021; Gana et al, 2020; Hollink et al, 2016; Ivanovski et al, 2020; Wojcik et al, 2019).…”

“…Thus, congenital structural anomalies are anticipated in AS; yet, they are known to be under‐reported. Previous structural anomalies reported in Alazami patients include cleft palate (Das et al, 2021; Hollink et al, 2016), atrial septal defect (Imbert‐Bouteille et al, 2019), genito‐renal anomaly (Das et al, 2021; Dateki et al, 2018), and ocular anomaly (Das et al, 2021; Imbert‐Bouteille et al, 2019). The findings in our cohort emphasize the importance of screening for structural anomalies as (4/12) patients had atrial septal defect, (6/12) patients had genito‐renal anomaly, and (7/12) patients have an ocular anomaly.…”

“…Since the initial description by Alazami and colleagues, many other cases from different ethnicities have been described in the literature (Bajafar et al, 2019; Das et al, 2021; Dateki et al, 2018; Elmas et al, 2019; Gana et al, 2020; Hollink et al, 2016; Holohan et al, 2016; Hosseini et al, 2019; Imbert‐Bouteille et al, 2019; Ivanovski et al, 2020; Kazemi et al, 2020; Ling et al, 2016; Wojcik et al, 2019). The phenotype has been revised as a syndromic cause of autosomal recessive intellectual disability with distinctive facial dysmorphology, variable progressive growth restriction, and significant speech and language delay.…”

Patient with Phenylketonuria and Intellectual Disability—Problem Not Always Caused Exclusively by Insufficient Metabolic Control (Coexistence of PKU and Alazami Syndrome)

“…Dysmorphic features include a triangular face with malar hypoplasia, deep-set eyes with narrow palpebral fissures, sparse eyebrows, wide nasal bridge, short philtrum, full lips and widely spaced teeth [ 10 ]. Occasionally, some common features such as low-set ears, prominent forehead, high palate and micrognathia are described [ 10 , 11 ]. In most cases disproportionate mild microcephaly compared with severe short stature is observed, too [ 10 ].…”

“…In most cases disproportionate mild microcephaly compared with severe short stature is observed, too [ 10 ]. Additionally, congenital heart defects and hypospadias have been reported [ 5 , 11 ]. Patients may present with a variety of behavioural disorders, such as excessive agitation, aggressiveness, self-stimulation and autistic features.…”