Delineating the phenotypic spectrum of hyperphosphatasia with mental retardation syndrome 4 in 14 patients of Middle‐Eastern origin

Abstract

Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) is a rare autosomal recessive condition caused by an impairment of glycosylphophatidylinositol biosynthesis. The cardinal features of HPMRS4 include; characteristic facial features, severe intellectual disability and various neurologic abnormalities. We report here detailed clinical, biochemical, and molecular findings of 14 patients clinically suspected to have HPMRS4, from three Middle-Eastern Countries;Saudi Arabia, Qatar, and Oman. All patients in our series presented with the cardinal features pointing to HPMRS4 and with an elevated alkaline phosphatase level. Five patients had megalocornea, which have been reported recently in an Arab patient. Additionally, fracture, bilateral coxa valga, camptodactyly, truncal obesity, and hyperpigmented macules of the upper thigh, each was seen once and was not described before with HPMRS4. Additional clinical and radiological findings are described, supporting the novel clinical and radiological findings recently described in Egyptian patients.

A Novel PGAP3 Gene Mutation-Related Megalocornea Can Be Misdiagnosed as Primary Congenital Glaucoma

“…After some time, when her other clinical features became prominent, further investigations revealed the mutation, and she was labeled with HPMRS4. To our knowledge, megalocornea in HPMRS4 was only reported in two previously published reports; both were in Middle-Eastern patients [ 4 , 17 ]. One of them was published in 2018 and described 14 patients with HPMRS4; five of them had megalocornea [ 4 ].…”

“…To our knowledge, megalocornea in HPMRS4 was only reported in two previously published reports; both were in Middle-Eastern patients [ 4 , 17 ]. One of them was published in 2018 and described 14 patients with HPMRS4; five of them had megalocornea [ 4 ].…”

“…Three of which were nonsense, 13 were missense, two were small insertion, two were deletion, one mutation was splicing, and one was regulatory. The most commonly reported clinical features of HPMRS are hypertelorism, upslanted palpebral fissures, broad nasal bridge, short nose, seizure disorder, long philtrum, and cleft-palate [3][4][5][6][7][8][9][10][11][15][16]. There are certain uncommon features that were reported in HPMRS4 such as gum hypertrophy, ear pits, and large anterior fontanelle [9].…”

“…Balobaid et al delineated the phenotypic spectrum of HPMRS4 in 14 Middle-Eastern patients [ 4 ]. They also reviewed the previously published mutations of the PGAP3 gene.…”