Supplementary

Table S1. Comprehensive list of FGD1 mutations in Aarskog-Scott syndrome and related disorders with faciogenital anomalies.

Exon DNA change Protein change Variant remark Disease Phenotypic features Age at Diagnosis 1 c.110C>T p.A37V Found once, non- MRX Mental retardation - recurrent change 4 c.935C>T p.P312L Found once, non- MRX Mental retardation - recurrent change 8 c.1555C>A p.Arg519Ser - FGDY - - 10 c.1842+1G>T p.(del) - FGDY - - 5 c.1139A>C p.Glu380Ala - FGDY Round face, hypertelorism, epicanthic folds, 3 widow’s peak, small nose with anteverted nares, long philtrum, cutaneous with and of the 4th and 5th fingers, right inguinal hernia, umbilical hernia, shawl scrotum, short stature and bilateral varus metatarsus 6 c.1205G>A p.Arg402Gln - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands, short stature, shawl scrotum, widow's peak, abnormal auricles 6 c.1223G>A p.Arg408Gln - FGDY Short stature, low weight, and normal cephalic 16 circumference. Inner canthal distance 2.7 cm (5th centile), interpupillary distance 5 cm (5th centile), and outer canthal distance 9.5 cm (90th centile), downslanting palpebral fissures with bilateral and strabismus, broad and bulbous nose, medial extension of eyebrows, dysmorphic and low set auricles, maxillary hypoplasia, ogival palatus, protuberant lips 6 c.1316_1319de p.Leu440Argfs*31 - FGDY Short stature and mild learning and behavioural 10 disabilities (hyperactivity and attention deficit). Hypertelorism (inner canthal distance 3.5 cm; 97th percentile – outer canthal distance 9.5 cm; 97th percentile), left palpebral ptosis, short nose with anteverted nostrils, long philtrum, posteriorly angulated low-set ears, prominent umbilicus, hyperextensible joints and brachydactyly with cutaneous II–V syndactyly 6 c.1316_1319del p.Leu440Argfs*31 - FGDY Long face, telecanthus (inner canthal distance 3.7 7 cm; 97th percentile – outer canthal distance 8.5 cm; 80th percentile), short nose with anteverted nostrils, long philtrum, micrognathia and posteriorly angulated low-set ears. Short stature, , hyperextensible joints, brachydactyly with cutaneous I–V syndactyly, single palmar creases, hypospadias and right cryptorchidism 6 c.1328G>T p.Arg443His - FGDY Widow’s peak, hypertelorism, epicanthic folds, 4.5 down-slanting palpebral fissures with bilateral palpebral ptosis, short and broad nose with anteverted nostrils, 4th and 5th fingers camptodactyly, shawl scrotum and inguinal hernias 6 c.1328G>T p.Arg443His - FGDY Short stature, frontal bossing, hypertelorism, 13 blepharoptosis, broad hands and feet , short fingers, interdigital webbing, hyperextensible proximal interphalangeal joints , flexion of distal interphalangeal joints, shawl scrotum 7 c.1392_1393insG p.(Lys465Glufs*5) - AAS - - 7 c.1396A>G p.Met466Val - FGDY Shawl scrotum, pectus excavatum, unilateral 8 clinodactyly V, and a characteristic over- extension of the proximal joint with flexion of the distal joint of the fingers. Toes II–IV displayed a valgus deviation, and the spacing between the first and second toe was increased and a unilateral brain malformation 8 c.1565G>A p.Arg522His - AAS Short stature, relative , ocular - hypertelorism, down-slanting palpebral fissures, ptosis of the upper eyelids, flat philtrum, bow shape of the upper lip and pointed chin, brachydactyly, typical hyperextensibility of the proximal and incomplete extensibility of the distal interphalangeal joints, and transverse palmar crease. Also noted: umbilical hernia, dorsal groove of the penis 8 c.1565G>A p.Arg522His - AAS Short stature, relative macrocephaly, ocular - hypertelorism, down- slanting palpebral fissures, ptosis of the upper eyelids, flat philtrum, bow shape of the upper lip and pointed chin, brachydactyly, typical hyperextensibility of the proximal and incomplete extensibility of the distal interphalangeal joints, and transverse palmar crease. Also noted: inguinal hernia and shawl scrotum 8 c.1590T>A p.Tyr530* - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands, short stature, shawl scrotum, interdigital webbing, camptodactily, widow's peak, ptosis, broad feet, cryptorchidism, inguinal/umbilical hernia 8 c.1620delC p.Asp540Glufs*11 - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands, short stature, crease below lower lip, interdigital webbing, short fifth finger/clinodactyly, camptodactily, ptosis, broad feet 9 c.1673C>G p.Ser558Trp - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands, short stature, shawl scrotum, crease below lower lip, short fifth finger/clinodactyly, widow's peak, ptosis, abnormal auricles, inguinal/umbilical hernia 10 c.1829G>A p.Arg610Gln - FGDY Short stature and normal intelligence with round - faces, prominent foreheads with widow's peak, hypertelorism, antimongoloid slant of palpebral fissures, bilateral ptosis, hypoplasia of the midface, short and broad nose with anteverted nostrils and long broad philtrum, small hands and feet. 12 c.1966C>T p.Arg656* - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands, short stature, shawl scrotum, crease below lower lip, short fifth finger/clinodactily, camptodactily, widow's peak, downward palpebral slant, abnormal auricles, joint hyperextension, broad feet, cryptorchidism, 13 c.2026_2028del p.Glu676del - FGDY Hypertelorism, short nose/anteverted nares, short - broad hands, short stature, shawl scrotum, crease below lower lip, widow's peak, downward palpebral slant, abnormal auricles, broad feet 15 c.2192delA p.Lys731Argfs*132 - FGDY Weight and height just below the 3rd centile, 2 round face, hypertelorism, ptosis of eyelids, and small nose with upturned nares, wide philtrum and hypoplastic auricles at their upper segment, pigeon chest. Short fingers with syndactyly of all fingers and camptodactyly of 3rd finger. Bilateral transverse line on both palms, and a single flexion crease on both 5th fingers, shawl scrotum with otherwise normal genitalia 15 c.2221G>T p.Glu741* - FGDY, Short stature, frontal bossing, hypertelorism, 4 Asperger broad hands and feet, short fingers, interdigital Syndrome webbing, hyperextensible proximal interphalangeal joints, flexion of distal interphalangeal joints, shawl scrotum 15 c.2242A>G p.Lys748Glu - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands 17 c.2530delG p.Val844Trpfs*19 - FGDY Hypertelorism, slight downward slanting 16 palpebral fissures, short nose, broad philtrum, broad mouth, short broad hand, shawl scrotum. The patient progressed through puberty satisfactorily attaining a normal height (175 cm). 3 c.529dupC p.Leu177Profs*40 - FGDY - 29 3 c.529dupC p.Leu177Profs*40 - FGDY Short stature, joint hypermobility, small and short 9 hands and feet, brachydactyly and camptodactyly 3 c.614G>T p.Ser205Ile - FGDY Impairment in expressive language and speech 11 articulation, emotional behaviour problems, short stature, moderate rhizomelia of upper and lower limbs, short hands with cutaneous syndactyly of fingers, surgically corrected right-sided cryptorchidism and over-riding scrotum, relative macrocephaly, frontal bossing 4 c.806delC p.Ala269Valfs*91 - FGDY Hypertelorism, short nose/ anteverted nares, short - broad hands, short stature, shawl scrotum, short fifth finger/clinodactyly, abnormal auricles, broad feet, cryptorchidism 4 c.944_975del p.Pro315Argfs*11 Probably de novo (not FGDY Dysmorphic facial appearance, shawl scrotum and 21 present in mother and short stature, hypertelorism (inner canthal sister) distance 3.9 cm; – outer canthal distance 11.5 cm), left palpebral ptosis and strabismus, short neck, camptodactyly and brachydactyly 4 c.945_946insC p.Ala316Argfs*4 Absent in maternal FGDY Short stature with occipitofrontal circumference 15 grandmother and three of 54 cm, widow’s peak, synophrys, inner canthal maternal aunts – distance of 3.5 cm and outer canthal distance 10 probably de novo or cm. Dysmorphic features include downslanting from parental palpebral fissures, palpebral ptosis, short and mosaicism convex nose, long philtrum, right maxillary hypoplasia with right microtia, curved linear dimple below the lower lip, short neck, pectus excavatum, brachydactyly with mild soft tissue webbing between the fingers, single crease in the fifth fingers 4 c.982delC p.His328Thrfs*32 The 982delC mutation FGDY Unusual facial appearance and short stature. 1.3 not present in hypertelorism (inner canthal distance 3.9 cm; phenotypically normal outer canthal distance 11.5 cm); antimongoloid mother (de novo or slant of palpebral fissures, widow’s peak, small maternal germline nose with anteverted nares, long philtrum, mosaicism) cutaneous syndactyly with brachydactyly and clinodactyly of the 5th fingers, transverse palmar crease, shawl scrotum, right cryptorchidism, small right inguinal hernia and an umbilical hernia. 1_18 c.1-?_2885+?del Complete deletion - FGDY Ptosis and camptodactyly, weight less than 5th 1.2 years percentile, height was 1st percentile and head circumference was 25th percentile. Posteriorly rotated ears, bilateral ptosis, ocular hypertelorism, downslanting palpebral fissures, small upturned nose, high arched palate, bilateral camptodactyly involving 3rd, 4th, and 5th fingers and mild shawl scrotum with right inguinal hernia. 9_12 c.1659+?_2044- ex9-12del, gross - FGDY Short stature, widow’s peak, hypertelorism, 3 ?del deletion downslanting palpebral fissures, ptosis of the upper eyelids and a short nose with anteverted nares, brachydactyly and cutaneous syndactyly of both hands and a shawl scrotum. 7 C.1392_1393INSg P.(Lys465Glufs*5) - AAS - - 11 c.1935+3A>C - IVS11 c.1935+3A>C, FGDY Hypertelorism, short nose/ anteverted nares, short - splicing broad hands and stature, shawl scrotum, crease below lower lip, short fifth finger/clinodactyly, widow's peak, ptosis, downslanting palpebral fissues, broad feet, prominent umbilicus 14 c.2091T>C - Recurrent (three MRX - - individuals) 14 c.2136A>G - Recurrent MRX - -

Key: FGDY: Faciogenital dysplasia, MRX: Mental retardation X-linked,

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