Table 1 Clinical description of patients studied (patient data as provided by the clinician at the reference centre)

PHP01

(P9 [30])

7y

12y6m

M

Yes (and TSH)

N

ND

Severe and generalized

Behavioural disorder

−1,5SD

+ 1,3SD

broad face with widely spaced eyes

maxillonasal hypoplasia, severe hypoplasia of the skull, thickened calvarium, increased size of the jaw with severe malocclusion

No

ND

–

PHP02

(P8 [30])

6y6m

8y6m

F

Yes

P↑

ND

Severe and generalized

No

-2.5SD

0.2SD

broad face with widely spaced eyes,maxillonasal hypoplasia

severe hypoplasia of the skull, thickened calvarium

No

Yes

pigmented skin spots

PHP03

(P14 [30])

3y

3y10m

F

Yes (and TSH)

N

N

Severe and generalized

No

-1.8SD

0.9SD

broad face with widely spaced eyes

maxillonasal hypoplasia, severe hypoplasia of the skull, thickened calvarium, dysplasia of both hips

yes

ND

–

PHP04

13y

18y

F

Yes

N

ND

Severe and generalized

(no X-ray)

No

135 cm (-3SD)

ND

Flat round face

genu valgum, Madelung deformity, exostosis in the knee (9y)

ND

ND

osteoporosis

PHP05

–

3y9m

F

Yes (and TSH)

ND

Low levels

Severe and generalized

ND

45 cm (−2.7 SD)

+ 1.8 SD

broad nasal root

–

Yes (5-6y)

ND

short neck, café-au-lait spots

PHP06

[31]

42y

45y

F

No

(after Vit. D treatment) (and FSH

N

Low levels at first

Severe and generalized

severe

139 cm (− 4 SD)

>2SD

broad face with flattening of nasal ridge, facial dysostosis, spaced eyes

maxillonasal hypoplasia

–

ND

short neck, hyperinsulinism

PHP07

(P1 [33])

31y

40y

F

Yes (and low GH)

N

N

MT: III-V

outcarving cones of MP & TP

learning difficulties (no test)

141.5 cm (−4 SD)

42.7 kg/m2 (> > 2SD)

round face, thin upper lip and prominent lower lip, pear-shaped nose

stubby fingers and toes

–

tooth hypoplasia

sparse hair, polyarthrosis, arthralgias of both hips and knees

PHP08

(P2 [33])

–

11y

F

N

N

N

MT: II-V outcarving cones of MP & BP

N

139.8 cm (-1SD)

25.6 kg/m2 (+ 1.96 SD)

long flat philtrum, and thin upper lip, pear-shaped nose, protruding ears

–

ND

ND

sparse hair, laterally sparse eyebrows, type 2 diabetes

PHP09

–

32y

F

No

N

ND

Generalized shortening, severe outcarving of the epiphyses

ND

152 cm (-2SD)

ND

thin upper lip, long philtrum, pear-shaped nose, sparse, eyebrows, prominent forehead

–

–

ND

Sparse hair

PHP09-D

5m

9m

F

No

N

ND

NA

ND

−2.8 SD

−2.4SD

thin upper lip, long philtrum, rounded nose, sparse eyebrows, prominent forehead, separated eyes

ND

ND

ND

Sparse hair

PHP10

–

33y

F

No

N

ND

Generalized shortening, stubby fingers

(no X-ray received)

ND

ND

ND

thin upper lip, long philtrum, pear-shaped nose

ND

ND

ND

Sparse hair

PHP10-S

1y7m

M

No

N

ND

NA

ND

Growth failure

Growth failure

thin upper lip, long philtrum, rounded nose, sparse eyebrows, low-set ears

ND

ND

ND

Sparse hair, strabismus

PHP10-D

6y

F

No

N

ND

Yes (no X-ray)

ND

ND

ND

thin upper lip, long philtrum, rounded nose, sparse eyebrows, anteverted ears

ND

ND

ND

Sparse hair, strabismus

PHP11

(P3 [34])

11.5y

12y

F

N

N

N

MT: IV

N

−1 SD

N

No

–

Yes (13.5 years)

(final height below target height)

No

Advanced bone age

PHP12

[35]

10y

12y

F

No

N

ND

MT: II-V

TP: I & III

No

148.7 cm (−0.4SD)

1.7 SD

round face, long philtrum

–

Yes (12y)

No

short neck, descended and widely separated nipples

PHP13

28y

–

F

No

N

ND

Severe

(especially IV & V MT)

(no X-ray received)

Yes

139 cm (-4SD)

p3-p10

small saddle nose, prominent forehead, epicanthal folds, upward slanting palpebral fissures, low and dysplastic ears

maxillonasal hypoplasia with severe prognathism

No

micrognatia

fine and sparse hair, parse eyebrows, café-au-lait spots, severe myopia

PHP14

10y

–

F

No

N

ND

MT: V

(no X-ray received)

ND

130.6 cm (-1SD)

85th

ND

clinodactyly, cone-shaped phalangeal epiphyses

ND

ND

–

PHP15

17y

–

F

No

N

ND

MT: IV

(no X-ray received)

No

p45

p75-p90

round face, facial asymmetry

–

ND

ND

hypothyroidism

PHP16

16y

–

M

No

(after Vit. D treatment)

N

(after Vit. D treatment)

Low levels at first

MT: IV & V

(no X-ray received)

ND

ND

(Obesity)

–

–

–

Dental malformations

acanthosis nigricans, short neck, hyperinsulinism

PHP17

9y7m

–

F

No

N

ND

MP: II-V at least. (BDA1?)

ND

−2,2SD

+ 2,7SD

prominent forehead, depressed nasal root

rhizomelia

No

ND

increased subarachnoid space, ventriculomegaly, bilateral frontotemporal cortical atrophy, ectopic neurohypophysis

PHP18

9y11m

–

M

No

N

N

Stubby digits

MT: III-IV at least

No

117 cm (−3,38SD)

N

flattening of nasal ridge

stocky build, hip hypoplasia, horizontal acetabulum, varum deformity, shortened tibia and femur, decreased interpedicular distance, scoliosis, bone dysplasias

ND

ND

–

PHP19

65y

–

F

No

N

N

MT: IV

No

(SS)

ND

big nose, thin upper lip

–

–

ND

–

PHP20

15y5m

–

M

No

N

N

MT: IV & V

No

143,5 cm (−3,9SD)

+ 4,22SD

ND

–

ND

ND

delayed puberty

PHP21

10y

–

F

N (TSH mildly increased)

N

ND

MT: IV; TP: I

No

p30

N

prominent forehead, periorbital hyperpigmentation, long palpebral fissure, deep philtrum, thick eyebrows

–

ND

ND

–

PHP22

13y

–

F

N

N

ND

MP: II & V (BDA4?)

No

p50

+ 1.5SD

N

Bilateral cubitus valgus, short forearms, exostosis in both tibia, dorsolumbar hyperkyphosis in D12-L1

ND

N

bicornuate uterus, short neck, wide thorax

PHP23

8y1m

–

F

No

N

N

MT: IV & V (mild) and clinodactyly of V

Mild

+3SD

> + 3SD

round face, thin upper lip, pear-shaped nose, sparse, arched eyebrows

–

ND

ND

sparse hair, epilepsy